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On episode #58 of the Infectious Disease Puscast, Daniel and Sara review the infectious disease literature for the weeks of 6/20 – 7/3/24. Host: Daniel Griffin and Sara Dong Subscribe (free): Apple Podcasts, RSS, email Become a patron of Puscast! Links for this episode Viral Drink more coffee, reduces risk for SARS-C0V-2 infection (Cell & Bioscience) Cannabis, tobacco…smoking in general NOT good for preventing COVID-19 (JAMA Network OPEN) EBV and KSHV caused HIV associated cancers and lymphoproliferative disorders (Clinical Microbiology Reviews) Where in the CNS can dolutegravir, tenofovir, lamivudine and efavirenz be found? (JID) Therapeutic management of Varicella-Zoster virus meningitis (OFID) Bacterial Carbapenem use in extended-spectrum cephalosporin-resistant Enterobacterales infections (LANCET Infectious Diseases) IDSA guidelines (Columbia University) Guideline-Concordant Therapy for community-acquired pneumonia in the Hospitalized Population (OFID) Interpretive Criteria piperacillin/tazobactam susceptibility test for Enterobacterales (CID) FDA approval forCAPVAXIVE (FDA) 21 valent pneumococcal vaccine approved (Nature Reviews drug discovery) Antimicrobial resistant Staphylococcus aureus isolates (JAMA Network Open) Broad-spectrum antibiotic use for suspected community-onset sepsis (JAMA Network Open) Fungal The Last of Us ( Wikipedia) Challenges to vaccinating against coccidioidomycosis (OFID) Cryptococcosis: the story (OFID) Pneumocystis pneumonia: clinical spectrum, prophylaxis and delayed treatment (Intensive Care Medicine) Improve utilization of 1,3 β-D-glucan Testing(OFID) Music is by Ronald Jenkees
Aaron Ladd from KSHV out in Kansas City joins us to preview the Game from the Chiefs side of things!
Videos : Niall Ferguson – Woke Totalitarianism (0:19 to 18:14) Heather Mac Donald On How The Delusion of Diversity Destroys Our Common Humanity (11:14) Elon Musk: “Klaus Schwab Is LYING!!!” (9:45) Lycopene, lutein supplements show skin protection from within against UV radiation Leibniz Research Institute for Environmental Medicine (Germany), November 10, 2022 The study's findings, published in the British Journal of Dermatology , indicated that oral supplementation with the carotenoids changed the expression of genes that are indicators of oxidative stress, photo-dermatoses and photo-aging. “To the best of our knowledge we show here for the 1st time that (i) tomato nutrient complex as well as lutein do not only protect healthy human skin against UVB/A, but also against long wave UVA1 radiation, and (ii) that oral photo-protection of healthy human skin can be demonstrated at the level of HO-1, ICAM-1 and MMP-1 gene expression,” wrote researchers from IUF – Leibniz Research Institute for Environmental Medicine in Dusseldorf. Heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-1 (MMP-1) are reported to be UVA1/UVB radiation-inducible genes. “On top of that, as part of the photo-aging process we have evidence of the effect of our ingredients on the levels of expression of genes involved in collagen degradation, suggesting a link not only to skin health but also to skin appearance. This study suggests an effect of natural antioxidants on overall skin wellness, which is relevant for men and women in all age groups.” The new study included 65 healthy volunteers aged between 18 and 60. The participants were randomly assigned to randomly consume 20 mg per day of the tomato nutrient complex or placebo for 12 weeks, or 20 mg per day of lutein or placebo for 12 weeks. A two-week washout period separated the placebo and active intervention periods. At the beginning and at the end of each phase the skin was irradiated.Results of the placebo-controlled, double blinded, randomized cross-over study indicated that the tomato nutrient complex (TNC) totally inhibited the upregulation of HO-1, ICAM-1 and MMP1 mRNA by both UVA1 and UVA/B. On the other hand, lutein only completely inhibited gene expression if taken during the first 12 weeks (ie. prior to placebo), while a significantly smaller effect was observed if it was taken during the second 12 week phase (ie. after placebo), compared to TNC. (NEXT) Diallyl trisulfide in garlic induces apoptosis in primary effusion lymphoma Kyoto Pharmaceutical University (Japan), November 7, 2022 Reports from Kyoto Pharmaceutical University stated, “The allyl sulfides, including diallyl sulfide (DAS), diallyl disulfide (DAD), and diallyl trisulfide (DAT), contained in garlic and members of the Allium family, have a variety of pharmacological activities. Therefore, allyl sulfides have been evaluated as potential novel chemotherapeutic agents.” Our news editors obtained a quote from the research, “Here, we found that DAT inhibited nuclear factor-kB (NF-kB) signaling and induced apoptosis in primary effusion lymphoma (PEL), a subtype of non-Hodgkin's B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). We examined the cytotoxic effects of DAS, DAD and DAT on PEL cells. DAT significantly reduced the viability of PEL cells compared with uninfected B-lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9. DAT induced stabilization of IkBa, and suppressed NF-kB transcriptional activity in PEL cells. We examined the mechanism underlying DAT-mediated IkBa stabilization. The results indicated that DAT stabilized IkBa by inhibiting the phosphorylation of IkBa by the IkB kinase (IKK) complex. Furthermore, DAT induced proteasomal degradation of TRAF6, and DAT suppressed IKKb-phosphorylation through downregulation of TRAF6. It is known that activation of NF-kB is essential for survival of PEL cells. In fact, the NF-kB inhibitor BAY11-7082 induced apoptosis in PEL cells. In addition, DAT suppressed the production of progeny virus from PEL cells. The administration of DAT suppressed the development of PEL cells and ascites in SCID mice xenografted with PEL cells.” According to the news editors, the research concluded: “These findings provide evidence that DAT has antitumor activity against PEL cells in-vitro and in-vivo, suggesting it to be a novel therapeutic agent for the treatment of PEL.” (NEXT) PTSD May Speed Up Cellular Aging Boston University, November 13, 2022 From birth to death, a lot may change, but our DNA—the long, double-helix molecule that contains all of a person's genetic code—stays the same. The instructions for reading that code can shift, however, as the chemical tags on and around a DNA sequence change throughout our lives, depending on our age, environment, and behavior. This outside influence on how our genes are read and expressed by cells is called epigenetics—and researchers studying it have discovered clues that may show why some veterans live longer than others. In a new study of military veterans published in Translational Psychiatry, researchers report findings that suggest former service personnel with PTSD are at greater risk of early death. “Our study found that PTSD and comorbid conditions, like substance misuse, are associated with a cellular marker of early death found in DNA methylation patterns,” says Erika Wolf, a professor of psychiatry at the Boston University School of Medicine and senior author of the study. The study included two samples of veterans that had representative levels of trauma and other psychiatric conditions, like substance use and personality disorders. One group included 434 veterans in their early 30s, who had served in post-9/11 conflicts; the other group included 647 middle-age veterans and their trauma-exposed spouses. Both groups were assessed for a range of psychological conditions, and had blood drawn to obtain genetic information and to test for levels of a variety of inflammatory molecules. The results indicate PTSD symptoms were a factor in faster cellular aging—.36 of a year faster. So, for every year that the cells of someone without PTSD age, the cells of someone with more severe PTSD symptoms age a year and a third. (NEXT) Higher sense of purpose in life may be linked to lower mortality risk Boston University, November 14, 2022 Growing research indicates that one's purpose—i.e., the extent to which someone perceives a sense of direction and goals in their life—may be linked to health-protective benefits such as better physical functioning and lower risks of cardiovascular disease or cognitive decline. Now, a new study led by a Boston University School of Public Health (BUSPH) researcher found that people with higher levels of purpose may have a lower risk of death from any cause, and that this association is applicable across race/ethnicity and gender. Published in the journal Preventive Medicine, the study results did suggest that this association is slightly stronger among women than it is among men, but there was no significant difference by race/ethnicity. “In another study I led, we found that the effect of purpose on lowering all-cause mortality may differ by socioeconomic status. In this study, we extended the prior evidence and found that the beneficial effect of purpose persisted regardless of gender and race/ethnicity.” For the study, the team assessed self-reported sense of purpose among more than 13,000 people, based on the “purpose in life” of the Ryff Psychological Well-being Scales, a widely used tool that measures different aspects of well-being and happiness. The researchers also examined mortality risk over an eight-year period beginning between 2006-2008. The results showed that people with the highest sense of purpose indicated the lowest risk of death (15.2 percent mortality risk), compared to people with the lowest sense of purpose (36.5 percent mortality risk). The team also gathered data on additional factors that can influence health, such socioeconomic status, other demographic characteristics, baseline physical health, and depression, and found that an increase in these factors was also associated with increases in a higher sense of purpose. (NEXT) Hibiscus compound shows anti-Alzheimer disease activity Pohang University of Science and Technology, November 16 2022. A report published in Alzheimer's Research & Therapy revealed that gossypetin, a flavonoid occurring in the calyx of the hibiscus flower, activates a process that reduces brain accumulation of amyloid beta, a protein that clumps to form toxic brain plaques in people with Alzheimer disease. Gossypetin has been reported to have antioxidant, antiatherosclerotic and anticancer effects. Earlier research had suggested a benefit for gossypetin, which is structurally similar to quercetin, against the aggregation of amyloid beta and tau proteins that occurs in Alzheimer disease. However, gossypetin's action in animal models of the disease had not been evaluated. Researchers at Pohang University of Science and Technology administered gossypetin or a control substance to mice that were bred to develop a condition similar to that of Alzheimer disease in humans. After 13 weeks of daily treatment, mice that received the flavonoid had less amyloid beta in the brain's hippocampus (an area involved in memory and learning) and cortex in comparison with the control mice. Gossypetin-treated animals also demonstrated better spatial learning and memory than untreated mice. Rather than affecting the production of amyloid beta, the research team found that gossypetin helped clear it by enhancing the scavenging ability of the brain's immune cells, which are known as microglia. Microglia normally consume amyloid beta but can become exhausted by continual exposure, which leads to a chronic damaging inflammatory reaction. (NEXT) Over a billion young people are potentially at risk of hearing loss from headphones, earbuds, loud music venues Mayo Clinic, November 15, 2022 More than 1 billion teens and young people are potentially at risk of hearing loss because of their use of headphones and earbuds and attendance at loud music venues, concludes a pooled data analysis of the available evidence, published in the open access journal BMJ Global Health. The World Health Organization (WHO) estimates that over 430 million people worldwide currently have disabling hearing loss. Young people are particularly vulnerable because of their use of personal listening devices (PLDs), such as smartphones, headphones and earbuds, and attendance at loud music venues, amid poor regulatory enforcement. Previously published research suggests that PLD users often choose volumes as high as 105 dB while average sound levels at entertainment venues range from 104 to 112 dB, exceeding permissible levels (80 dB for adults; 75 dB for children) even if for very short periods of time. A group of 33 studies, corresponding to data from 35 records and 19,046 participants, was included; 17 records focused on PLD use and 18 focused on loud entertainment venues. The pooled data analysis indicates that the prevalence of unsafe listening practices from PLD use and attendance at loud entertainment venues is common worldwide—24% and 48%, respectively, among teens and young people. Based on these figures, the researchers estimate that the global number of teens and young adults who could potentially be at risk of hearing loss as a result ranges from 0.67 to 1.35 billion.
In her second talk, Glaunsinger explores gene expression control by viruses like Kaposi's sarcoma herpesvirus (KSHV), a frequent cause of cancer in AIDS patients. KSHV stimulates degradation of mRNA by encoding a nuclease, SOX, which is able to target a broad set of mRNAs for degradation yet cleaves them at specific sites recognized by a combination of RNA sequence and structure. Glaunsinger then describes how widespread mRNA degradation by viral nucleases such as SOX causes redistribution of RNA binding proteins in the cell and restricts mRNA transcription by RNA polymerase II. Thus, alterations to the rate of mRNA decay can have ripple effects in the cell that influence upstream events in gene expression.
In her second talk, Glaunsinger explores gene expression control by viruses like Kaposi’s sarcoma herpesvirus (KSHV), a frequent cause of cancer in AIDS patients. KSHV stimulates degradation of mRNA by encoding a nuclease, SOX, which is able to target a broad set of mRNAs for degradation yet cleaves them at specific sites recognized by a combination of RNA sequence and structure. Glaunsinger then describes how widespread mRNA degradation by viral nucleases such as SOX causes redistribution of RNA binding proteins in the cell and restricts mRNA transcription by RNA polymerase II. Thus, alterations to the rate of mRNA decay can have ripple effects in the cell that influence upstream events in gene expression.
REBEL SELECTION #14 MIX: MŌKSHV / FROM OUTER SPACE ARTWORK: LIZZIE (@_lizzieart) Con la quattordicesima edizione della Rebel Selection approdiamo finalmente anche in Francia e vi presentiamo un'artista super emergente MŌKSHV Dj e produttrice francesce con background musicale molto etorogeneo, tanto che per 10 anni ha suonato violino e pianoforte influenzando molto l'orecchio con musica classica. La scoperta dell'elettronica sfonda confini del suono che vuole assolutamente esplorare portandola a creare i propri suoni e i propri samples con i sintetizzatori. Ispirata dal paradosso dell'universo, cercando di connettere la luce all'oscurità che sono l'opposto e la stessa cosa, caratterizza le sue produzioni e i sui mix con un tocco rave e dark che sfocia spesso in attimi di luce ed energia, creando quel contrasto sensoriale che cattura l'ascoltatore e risveglia le menti con finezza. La Rebel Selection #14 tra poco sarà online sul nostro canale SoundCloud. MIX: MŌKSHV ARTWORK: Lizzie VISUAL: Busta Tilt ____________________stay safe, stay strong, stay strike_____________________ Follow Strike On pages: www.facebook.com/strikeonofficial/ www.instagram.com/strikeon_music/
In this “viral” episode, Jocelyn and Bradley sit down with Lisa Poppe, a Ph.D. student working in the—whoa, wait, WHAT? Indeed, as Lisa explains, everyone does have herpes, but not all the same kind. At the Nebraska Center for Virology, Lisa studies KSHV, a herpes virus associated with a type of cancer called Kaposi sarcoma. As they explore the big, small world of viruses, the friends discuss the science behind creating effective vaccines; why some viruses are particularly challenging to develop vaccines for; how storytelling and mutual respect are critical to fostering productive dialogue between scientists and non-scientists about vaccine effectiveness; and why The Prisoner of Azkaban is the best Harry Potter book. Join us, friends, for a freewheeling inquiry into our microscopic masters of the universe, from herpes to Hogwarts.Learn more about Lisa Poppe and her research:Nebraska Center for Virology: https://www.unl.edu/virologycenter/charles-wood-phdTwitter: @whatuppoppeFind Science! With Friends: ●Twitter: https://twitter.com/SciWithFriends●Facebook: https://www.facebook.com/SciWithFriends/Contact Science! With Friends (especially if you’re a scientist interested in a lively conversation about your science and science stories):●Gmail: sciwithfriends@gmail.com Produced by Basement Creators NetworkSound Editing by Vince Ruhl
www.traceymaxfield.com Tracey Maxfield is a nurse with over 36 years’ experience. She experienced her first episode of clinical depression in her twenties and lived with chronic depression ever since. However, nothing prepared her for the acute depressive episode she experienced in 2015. After enduring years of intense work place stress, harassment and bullying, she plummeted into an abyss of darkness, hopelessness and despair the likes of which she had never experienced before. Encouraged by a psychologist, Tracey started a Blog, Escaping the Rabbit Hole: my life with depression, to better help her friends understand her depression. Over time, Tracey began to heal and found that out of the darkness and despair, there is hope, there is life after depression. Since the release of her book, Escaping the Rabbit Hole: my journey through depression (www.traceymaxfield.com), Tracey has become a staunch advocate for Mental Illness and Mental Health Awareness and Bullying and completed the course, Bringing Mental Health to Schools. She has met with teenagers ages 11 to 15 years to talk about bullying and mental illness and has appeared on numerous podcasts in the USA, Canada and UK, live radio shows and ABC KOMO News 4, KSHV 45, and NBC News 6 television shows. In June, Tracey was featured in a series of articles by HelloCare magazine in Australia. In September, Tracey embarked on a new life journey, she sold her home, donated most of her possessions to various charities and made a commitment to try and make a difference in the world and is spending six months traveling in the USA, talking about mental illness and bullying in children and teenagers. Her philosophy is to Engage children and teenagers, to Educate them about mental illness and bullying and to Empower them to develop confidence and skills to continue to move ahead in their own life journey. Tracey completed the Global 7/7 Challenge and recorded 7 days/7 videos on mental illness www.traceymaxfield.fyi.to/changingthefaceofmentalillness and bullying in children and teenagers www.traceymaxfield.fyi.to/helptraceystopbullying. In February, Tracey is heading to Kansas and Florida to appear on TV/radio shows and give talks at local schools. She is also one of the ‘Break Out’ presenters at the TEACH 2019 Conference in Jacksonville, Florida on March 2, 2019.
WOW. What an impactful episode full of so much knowledge, passion, emotion, and discussion about mental health within our future generations. We cover mental health, depression, bullying public school systems, medication, natural solutions, meditation, awareness, trust, and more!! Tracey experienced her first episode of clinical depression in her twenties and lived with chronic depression ever since. However, nothing prepared her for the acute depressive episode she experienced in 2015. After enduring years of intense work place stress, harassment and bullying, she plummeted into an abyss of darkness, hopelessness and despair the likes of which she had never experienced before. Encouraged by a psychologist, Tracey started a Blog, Escaping the Rabbit Hole: my life with depression, to better help her friends understand her depression. Over time, Tracey began to heal and found that out of the darkness and despair, there is hope, there is life after depression. Since the release of her book, Escaping the Rabbit Hole: my journey through depression (www.traceymaxfield.com), Tracey has become a staunch advocate for Mental Illness and Mental Health Awareness and Bullying and completed the course, Bringing Mental Health to Schools. She has met with teenagers ages 11 to 15 years to talk about bullying and mental illness and has appeared on numerous podcasts in the USA, Canada and UK, live radio shows and ABC KOMO News 4, KSHV 45, and NBC News 6 television shows. In June, Tracey was featured in a series of articles by HelloCare magazine in Australia. In September, Tracey embarked on a new life journey, she sold her home, donated most of her possessions to various charities and made a commitment to try and make a difference in the world and is spending six months traveling in the USA, talking about mental illness and bullying in children and teenagers. Her philosophy is to Engage children and teenagers, to Educate them about mental illness and bullying and to Empower them to develop confidence and skills to continue to move ahead in their own life journey. Tracey completed the Global 7/7 Challenge and recorded 7 days/7 videos on mental illness www.traceymaxfield.fyi.to/helptraceystopbullying (http://www.traceymaxfield.fyi.to/helptraceystopbullying) . In February, Tracey is heading to Kansas and Florida to appear on TV/radio shows and give talks at local schools. She is also one of the ‘Break Out’ presenters at the TEACH 2019 Conference in Jacksonville, Florida on March 2, 2019. Born in Wales, U.K. Tracey moved to Canada in 1987. She currently lives in the Okanagan Valley in beautiful British Columbia. Escaping the Rabbit Hole: my journey through depression is her first book and has received international rave reviews. Is is available at Barnes & Noble, www.BOL.com, www.BookDepositorycom, and on Amazon in soft cover, kindle and audio book.
Tracey Maxfield Tracey Maxfield is a nurse with over 36 years’ experience. She is certified in gerontology and dementia care and is a regular guest on well-known author and radio host Peter Rosenberger’s show Hope For the Caregiver on WLAC and iHeart Radio in Nashville, Tennessee. Tracey has written articles on dementia care, medical research and mental illness/bullying in teenagers. She is the Purple Angel Dementia Ambassador for the Okanagan. B.C. Tracey experienced her first episode of clinical depression in her twenties and lived with chronic depression ever since. However, nothing prepared her for the acute depressive episode she experienced in 2015. After enduring years of intense work place stress, harassment and bullying, she plummeted into an abyss of darkness, hopelessness and despair the likes of which she had never experienced before. Encouraged by a psychologist, Tracey started a Blog, Escaping the Rabbit Hole: my life with depression, to better help her friends understand her depression. Over time, Tracey began to heal and found that out of the darkness and despair, there is hope, there is life after depression. Since the release of her book, Escaping the Rabbit Hole: my journey through depression (www.traceymaxfield.com), Tracey has become a staunch advocate for Mental Illness and Mental Health Awareness and Bullying and completed the course, Bringing Mental Health to Schools. She has met with teenagers ages 11 to 15 years to talk about bullying and mental illness and has appeared on numerous podcasts in the USA, Canada and UK, live radio shows and ABC KOMO News 4, KSHV 45, and NBC News 6 television shows. In June, Tracey was featured in a series of articles by HelloCare magazine in Australia. In September, Tracey embarked on a new life journey, she sold her home, donated most of her possessions to various charities and made a commitment to try and make a difference in the world and is spending six months traveling in the USA, talking about mental illness and bullying in children and teenagers. Her philosophy is to Engage children and teenagers, to Educate them about mental illness and bullying and to Empower them to develop confidence and skills to continue to move ahead in their own life journey. Tracey completed the Global 7/7 Challenge and recorded 7 days/7 videos on mental illness www.traceymaxfield.fyi.to/changingthefaceofmentalillness and bullying in children and teenagers www.traceymaxfield.fyi.to/helptraceystopbullying. In February, Tracey is heading to Kansas and Florida to appear on TV/radio shows and give talks at local schools. She is also one of the ‘Break Out’ presenters at the TEACH 2019 Conference in Jacksonville, Florida on March 2, 2019. Born in Wales, U.K. Tracey moved to Canada in 1987. She currently lives in the Okanagan Valley in beautiful British Columbia. Escaping the Rabbit Hole: my journey through depression is her first book and has received international rave reviews. Is is available at Barnes & Noble, www.BOL.com, www.BookDepositorycom, and on Amazon in soft cover, kindle and audio book. Listen to another #12minconvo
On this Gratitude:UnFiltered hosted by Joshua T Berglan……an update on the camera store and……… Tracey Maxfield is a nurse with over 36 years’ experience. She is certified in gerontology and dementia care and is a regular guest on well-known author and radio host Peter Rosenberger’s show Hope For the Caregiver on WLAC and iHeart Radio in Nashville, Tennessee. Tracey is the Purple Angel Dementia Ambassador for the Okanagan. B.C. Tracey experienced her first episode of clinical depression in her twenties and lived with chronic depression ever since. However, nothing prepared her for the acute depressive episode she experienced in 2015. After enduring years of intense work place stress, harassment and bullying, she plummeted into an abyss of darkness, hopelessness and despair the likes of which she had never experienced before. Encouraged by a psychologist, Tracey started a Blog, Escaping the Rabbit Hole: my life with depression, to better help her friends understand her depression. Over time, Tracey began to heal and found that out of the darkness and despair, there is hope, there is life after depression. Since the release of her book, Escaping the Rabbit Hole: my journey through depression (www.traceymaxfield.com), Tracey has become a staunch advocate for Mental Illness and Mental Health Awareness and Bullying and completed the course, Bringing Mental Health to Schools. She has met with teenagers ages 11 to 15years to talk about bullying and mental illness and has appeared on numerous podcasts in the USA, Canada and UK, live radio shows and ABC KOMO News 4, KSHV 45, and NBC News 6 television shows. In June, Tracey was featured in a series of articles by HelloCare magazine in Australia. In September, Tracey embarked on a new life journey, she sold her home, donated most of her possessions to various charities and made a commitment to try and make a difference in the world and is spending six months traveling in the USA, talking about mental illness and bullying in children and teenagers. Her philosophy is to Engage children and teenagers, to Educate them about mental illness and bullying and to Empower them to develop confidence and skills to continue to move ahead in their own life journey. Tracey completed the Global 7/7 Challenge and recorded 7 days/7 videos on mental illness www.traceymaxfield.fyi.to/changingthefa… and bullying in children and teenagers www.traceymaxfield.fyi.to/helptraceysto… She is scheduled to speak at the TEACH 2019 Conference in Jacksonville, Florida in March 2019. Born in Wales, U.K. Tracey moved to Canada in 1987. She currently lives in the Okanagan Valley in beautiful British Columbia. Escaping the Rabbit Hole: my journey through depression is her first book and has received international rave reviews. Is is available at Barnes & Noble, www.BOL.com, www.BookDepositorycom, and on Amazon in soft cover, kindle and audio book.
Patrick Moore returns to TWiV to discuss the discovery from the Chang-Moore laboratory of circular RNAs in cells infected with herpesviruses. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, and Kathy Spindler Guest: Patrick Moore Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Please take the TWiV listener survey ASV 2019 European Congress of Virology 2019 ASM Clinical Virology Symposium Intel ISEF judges needed Cancer virology at Pitt Alice Huang’s DI particles (PubMed) Circular DNA tumor viruses make circular RNAs (PNAS) Backsplice Image credit Timestamps by Jolene. Thanks! Weekly Science Picks Brianne – The herd to the rescue Alan – Magic Wings Butterfly Conservatory Dickson – 100,000 Genomes Project Kathy – Your Age on Other Worlds Vincent – Vitamin D and Prevention of Cancer and Cardiovascular Disease Pat – North Korea and Bioweapons Listener Pick Eric – The Molecular Basis of Life Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv
Patrick Moore returns to TWiV to discuss the discovery from the Chang-Moore laboratory of circular RNAs in cells infected with herpesviruses. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, and Kathy Spindler Guest: Patrick Moore Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Please take the TWiV listener survey ASV 2019 European Congress of Virology 2019 ASM Clinical Virology Symposium Intel ISEF judges needed Cancer virology at Pitt Alice Huang’s DI particles (PubMed) Circular DNA tumor viruses make circular RNAs (PNAS) Backsplice Image credit Timestamps by Jolene. Thanks! Weekly Science Picks Brianne – The herd to the rescue Alan – Magic Wings Butterfly Conservatory Dickson – 100,000 Genomes Project Kathy – Your Age on Other Worlds Vincent – Vitamin D and Prevention of Cancer and Cardiovascular Disease Pat – North Korea and Bioweapons Listener Pick Eric – The Molecular Basis of Life Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv
Since the release of her book, Escaping the Rabbit Hole: my journey through depression, Tracey Maxfield has become a staunch advocate for Mental Illness and Mental Health Awareness and Bullying and completed the course, Bringing Mental Health to Schools. She has met with teenagers ages 11 to 15 years to talk about bullying and mental illness and has appeared on numerous podcasts, live radio shows and ABC KOMO News 4, KSHV 45, and NBC News 6 television shows. In June, Tracey was featured in a series of articles by HelloCare magazine in Australia.In September, Tracey embarked on a new life journey: she sold her home, donated most of her possessions to various charities and made a commitment to try and make a difference in the world and is spending six months traveling in the USA, talking about mental illness and bullying in children and teenagers. Her philosophy is to Engage children and teenagers, to Educate them about mental illness and bullying and to Empower them to develop confidence and skills to continue to move ahead in their own life journey.Kara and I have read the book Escaping the Rabbit Hole: my journey through depression and it is excellent. I highly recommend you buy and read it, if you or anyone you care about is suffering, or has suffered, from depression. It's now available in paperback, Kindle and audiobook. If you enjoyed this episode, an iTunes review would be SO appreciated! It's super easy to do right within the Podcast app.SHOW NOTES: IMPORTANT LINKS Learn more about Tracey, her book Escaping the Rabbit Hole: my journey through depression, and her upcoming public appearances on her website.Tracey nominates Scott Davidson and Nick Kellet to come on the I Love Kelowna Podcast. Kara Rogers and I nominated Tracey. Follow me on Social Media:I Love Kelowna Podcast on FacebookInstagramLinkedinLuke Menkes RE/MAX KelownaMy Personal Facebook PageSupport the show (https://paypal.me/lukemenkes)
Host: Vincent Racaniello Guests: Dirk Dittmer, Cary Moody, Nat Moorman, Nancy Raab-Traub, Lishan Su, and Jennifer Webster-Cyriaque In the first of two shows recorded at the University of North Carolina in Chapel Hill, Vincent meets up with faculty members to talk about how they got into science, their research on DNA viruses, and what they would be doing if they were not scientists. View video of this episode at YouTube Become a patron of TWiV! This episode is brought to you by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and nonfiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. This episode is also brought to you by Drobo, a family of safe, expandable, yet simple to use storage arrays. Drobos are designed to protect your important data forever. Visit www.drobo.com to learn more. Listeners can save $100 on a Drobo system at drobostore.com by using the discount code Microbe100. Send your virology questions and comments to twiv@microbe.tv
Host: Vincent Racaniello Guest: Blossom Damania Vincent speaks with Blossom about her laboratory's research on Kaposi's sarcoma-associated herpesvirus, including how it transforms cells, the switch between lytic and latent replication, and its interaction with the innate immune system of the host. Links for this episode Damania Laboratory Modulation of cGAS-STING by KSHV (PNAS) KSHV vIRF1 interacts with ISG15 pathway member (J Virol) KSHV NLR homolog inhibits inflammasome (Science) KSHV inhibition of PI3K and mTOR (Blood) KSHV confers survival advantage to endothelial cells (Cancer Res) UNC Global Oncology Program Blossom on Twitter Video of this episode - view at YouTube Send your virology questions and comments to twiv@twiv.tv
Hosts: Vincent Racaniello, Britt Glausinger, and Eva Harris Vincent visits the University of California at Berkeley and speaks with Britt Glaunsinger and Eva Harris about their work on Kaposi's sarcoma associated herpesvirus and dengue virus. Thanks to the Microbiology Graduate Students for hosting me at their annual symposium, and especially to Emma, Lisa, and Zoe for their wonderful hospitality during my stay. Links for this episode: RNA element in IL-6 confers SOX resistance (J Virol) Dual uORFs regulate herpesviral translation (PLoS Path) Common viral strategy for RNA degradation (J Virol) KSHV SOX and Xrn1 together degrade host mRNAs (PLoS Path) Dengue treatment with Fc null antibodies (PLoS Path) Early clinical features of dengue in Nicaraguan children (PLoS Negl Trop Dis) Intrahuman dengue virus diversity (J Virol) Dynamics of dengue disease severity (Sci Transl Med) Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv
Hosts: Vincent Racaniello, T. Jack Morris, James Van Etten, and Charles Wood Vincent travels to the University of Nebraska to meet with members of the Nebraska Center for Virology and discuss their work on algal viruses, plant viruses, HIV and Kaposi's sarcoma herpesvirus. Links for this episode: The Nebraska Center for Viology Behind the scenes at TWiV 202 TWiV on Facebook Weekly Science Picks Charles - Rhabdovirus associated with hemorrhagic fever (PLoS Path)Vincent - Bacteriophage graffiti (jpg) Listener Pick of the Week Bob - Remembering Penny PinneoJanet - Penn and Teller on vaccinations (YouTube) Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.
Background: Murine gammaherpesvirus 68 (MHV-68) is used as a model to study the function of gammaherpesvirus glycoproteins. gp150 of MHV-68, encoded by open reading frame M7, is a positional homolog of gp350/220 of EBV and of gp35/37 of KSHV. Since it had been proposed that gp350/220 of EBV might be a suitable vaccine antigen to protect from EBV-associated diseases, gp150 has been applied as a model vaccine in the MHV-68 system. When analyzing the function of gp150, previous studies yielded conflicting results on the role of gp150 in latency amplification, and disparities between the mutant viruses which had been analyzed were blamed for the observed differences. Results: To further develop MHV-68 as model to study the function of gammaherpesvirus glycoproteins in vivo, it is important to know whether gp150 contributes to latency amplification or not. Thus, we re-evaluated this question by testing a number of gp150 mutants side by side. Our results suggest that gp150 is dispensable for latency amplification. Furthermore, we investigated the effect of vaccination with gp150 using gp150-containing exosomes. Vaccination with gp150 induced a strong humoral and cellular immune response, yet it did not affect a subsequent MHV-68 challenge infection. Conclusions: In this study, we found no evidence for a role of gp150 in latency amplification. The previously observed contradictory results on the role of gp150 in latency amplification were not related to differences between the mutant viruses which had been used.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
Wed, 21 Dec 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16088/ https://edoc.ub.uni-muenchen.de/16088/1/Scholz_Barbara.pdf Scholz, Barbara Antonie
The TWiV team speaks with Patrick Moore about his discovery, with Yuan Chang, of two human tumor viruses, Kaposi's sarcoma herpesvirus and Merkel cell polyomavirus.
Kaposi's sarcoma herpesvirus (KSHV) encodes a cluster of twelve micro (mi)RNAs, which are abundantly expressed during both latent and lytic infection. Previous studies reported that KSHV is able to inhibit apoptosis during latent infection; we thus tested the involvement of viral miRNAs in this process. We found that both HEK293 epithelial cells and DG75 cells stably expressing KSHV miRNAs were protected from apoptosis. Potential cellular targets that were significantly down-regulated upon KSHV miRNAs expression were identified by microarray profiling. Among them, we validated by luciferase reporter assays, quantitative PCR and western blotting caspase 3 (Casp3), a critical factor for the control of apoptosis. Using site-directed mutagenesis, we found that three KSHV miRNAs, miR-K12-1, 3 and 4-3p, were responsible for the targeting of Casp3. Specific inhibition of these miRNAs in KSHV-infected cells resulted in increased expression levels of endogenous Casp3 and enhanced apoptosis. Altogether, our results suggest that KSHV miRNAs directly participate in the previously reported inhibition of apoptosis by the virus, and are thus likely to play a role in KSHV-induced oncogenesis.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 12/19
Varicella zoster virus (VZV) is a member of the alphaherpesvirus subfamily and with a genome encoding 70 proteins the smallest of all human herpesviruses. Upon primary infection it causes varicella also called chickenpox in children. As a consequence, it reaches sensory nerve ganglia where latency is established. Upon reactivation it causes a secondary disease called Herpes zoster mostly in adults. Todate, VZV is the least studied human herpesvirus due to the lack of cell-free virus in culture, of virus-specific tools and an effective animal model. Therefore, many aspects of the VZV infection cycle, of latency and reactivation are poorly characterized. Moreover, the function of many proteins specific to VZV has not been identified. The goal of this research was to generate hybridoma clones as a permanent source of VZV specific antibodies and to use the antibodies produced to study the localisation of VZV proteins in the viral context on a proteome-wide level. To this end, a VZV ORFeome entry library was constructed using the Gateway® recombinational cloning technology. For VZV protein expression in E. coli, the entry library was subcloned into four different pET derived expression vectors providing either an N-terminal His6, a C-terminal His6, an N-terminal MBP, or an N-terminal GST tag. Following purification of 64 VZV proteins, mice were immunised and subsequently used to generate antibody producing hybridoma clones. So far, our clone collection contains 218 mother clones producing antibodies to 61 (87%) VZV proteins. In this clone collection 190 clones were identified as positive in Western blotting covering 57 VZV ORFs while 123 antibodies were tested positive in immunofluorescence covering 52 VZV ORFs. Using this novel antibody collection, the localisation of 52 (74%) proteins could be determined in the context of VZV infection 22 of which were analysed for the first time. In total, 20 ORFs were localised in the nucleus, 16 ORFs were present in the cytoplasm and 16 ORFs were found in both the nucleus and cytoplasm. Comparison of 41 core proteins present in HSV-1, VZV, CMV, EBV as well as KSHV showed excellent agreement in localisation of conserved glycoproteins, capsid and tegument proteins. Several immunodominant regions on the viral glycoproteins gK, gB, gL, gI, gE and the membrane associated phosphoprotein ORF24 were identified using the pepscan technique. This precious antibody collection gives access to various experimental approaches and will allow to unveil biological secrets in the field of Herpesvirology.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
Herpesviren exprimieren Micro-(mi)RNAs, welche die Expression von zellulären und viralen Genen beeinflussen. Das Genom des Kaposi Sarkom Assoziierten Herpesvirus (KSHV) kodiert ein Cluster von insgesamt 12 miRNAs, welche sowohl während der latenten, als auch während der lytischen Infektion exprimiert werden. Da bisher nur sehr wenige zelluläre Zielgene für KSHV miRNAs bekannt sind, war es das Ziel dieser Studie, Gene zu identifizieren, deren Expression durch virale miRNAs von KSHV beeinflusst wird. Zu diesem Zweck wurden KSHV miRNAs mit Hilfe eines lentiviralen Transduktionssystems in B-Zellen und in Endothelzellen exprimiert. Diese sind beide natürliche Wirtszellen für KSHV. Die dabei entstandenen Zelllinien wurden mit Hilfe von zwei unterschiedlichen experimentellen Ansätzen untersucht: Beim ersten Ansatz wurde das gesamte Expressionsprofil dieser Zellen mit Hilfe von Microarrays analysiert und, nach Filterung durch bioinformatische Methoden, wurden Kandidaten für eine Regulation durch virale miRNAs identifiziert. Das Ergebnis wurde anhand biochemischer Methoden validiert und zwei zelluläre Transkripte als Zielgene bestätigt. In funktionellen Analysen konnte gezeigt werden, dass KSHV miRNAs die Caspase 3 inhibieren und dadurch die Zellen vor Apoptose schützen. Im zweiten, weitaus effizienteren Ansatz, wurden die sogenannten RISC-Komplexe mit Hilfe von AGO2-spezifischen Antikörpern sowohl aus den KSHV miRNA exprimierenden Zellen als auch aus latent KSHV infizierten Zellen isoliert und die daran gebundenen mRNAs identifiziert. Der RISC-Komplex spielt die entscheidende Rolle bei der miRNA-induzierten Regulation und enthält neben Proteinkomponenten (u.a. Argonauten (AGO)-Proteinen) sowohl die aktiven miRNAs als auch die regulierten mRNAs. Nach Isolierung der gebundenen RNAs konnten mit dieser Methode 72 Gene als Zielgene für KSHV miRNAs identifiziert werden. Viele davon spielen eine wichtige Rolle in unterschiedlichen Prozessen wie Zellzykluskontrolle, in der Apoptose oder der mRNA-Prozessierung. Insgesamt 11 identifizierte Zielgene wurden mit Hilfe von real-time PCRs untersucht und 10 bestätigt. Mittels 3’UTR-Luciferase-Assays wurden 6 davon weiter analysiert und bestätigt. Für die Gene LRRC8D, NHP2L1 und GEMIN8 konnten die zuständigen KSHV miRNAs und die dazugehörigen Bindungsstellen auf dem Transkript identifiziert werden. Bei den letzteren beiden lagen diese interessanterweise nicht wie erwartet in der 3’UTR, sondern in dem kodierenden Bereich.
Viruses have evolved to evade the host's complement system. The open reading frames 4 (ORF4) of gammaherpesviruses encode homologs of regulators of complement activation (RCA) proteins, which inhibit complement activation at the level of C3 and C4 deposition. Besides complement regulation, these proteins are involved in heparan sulfate and glycosaminoglycan binding, and in case of MHV-68, also in viral DNA synthesis in macrophages. Here, we made use of MHV-68 to study the role of ORF4 during infection of fibroblasts. While attachment and penetration of virions lacking the RCA protein were not affected, we observed a delayed delivery of the viral genome to the nucleus of infected cells. Analysis of the phosphorylation status of a variety of kinases revealed a significant reduction in phosphorylation of the protein kinase Akt in cells infected with ORF4 mutant virus, when compared to cells infected with wt virus. Consistent with a role of Akt activation in initial stages of infection, inhibition of Akt signaling in wt virus infected cells resulted in a phenotype resembling the phenotype of the ORF4 mutant virus, and activation of Akt by addition of insulin partially reversed the phenotype of the ORF4 mutant virus. Importantly, the homologous ORF4 of KSHV was able to rescue the phenotype of the MHV-68 ORF4 mutant, indicating that ORF4 is functionally conserved and that ORF4 of KSHV might have a similar function in infection initiation. In summary, our studies demonstrate that ORF4 contributes to efficient infection by activation of the protein kinase Akt and thus reveal a novel function of a gammaherpesvirus RCA protein.
Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 06/19
ZUSAMMENFASSUNG Das Kaposi Sarkom assozierte Herpesvirus (KSHV) oder humanes Herpesvirus 8 (HHV-8) ist das zuletzt entdeckte humane Herpesvirus. Es gilt als das infektiöse Agens des Kaposi Sarkoms (KS), des Primary Effusion Lymphoms (PEL) und der Multicentric Castleman’s Disease (MCD). Ähnlich wie andere Spezies der Familie der Herpesviren kodiert es für die vergleichsweise hohe Zahl von mindestens 89 viralen Proteinen. Die meisten von ihnen wurden bisher nicht näher funktionell charakterisiert. Um nähere Informationen über die Funktion dieser Proteine zu erhalten, wurde im Rahmen dieser Studie eine genomweite Analyse von viralen Protein-Protein-Interaktionen durchgeführt. Zu diesem Zweck wurden alle KSHV „open reading frames“ kloniert und in einer Yeast two-hybrid (Y2H) Matrix Analyse auf Protein-Protein Interaktionen gescreent. In diesen Screen wurden sowohl komplette Proteine als auch Protein-Fragmente eingefügt, so dass insgesamt mehr als 12.000 virale Protein-Interaktionen getestet und letztlich 125 Protein-Interaktionen identifiziert werden konnten (71 % der bisher bekannten intraviralen Protein-Interaktionen konnten in dieser Studie ebenfalls nachgewiesen werden). Um die Ergebnisse aus dem Y2H-Screen abzusichern und um ein Set von „high-confidence“-Interaktionen zu generieren, wurden alle positiven Y2H-Interaktionen erneut duch Co-Immunoprezipitationen (Co-IP) getestet. Auf diese Weise konnten zirka 50 % der Interaktionen bestätigt werden. Die erweiterte bioinformatische Analyse des viralen Protein-Interaktionsnetzwerkes zeigte deutliche Unterschiede zu zellulären Netzwerken auf. Diese Studie bietet zudem eine Vielzahl neuer biologischer Ansätze an, welche es künftig noch im Detail zu untersuchen gilt. Weiter könnten diese Untersuchungsergebnisse zu einem vertieften Verständnis der viralen Pathogenese und möglicherweise zu neuen Ansatzpunkten für therapeutische Strategien führen.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 02/06
Kaposi´s sarcoma-associated herpesvirus (KSHV) is involved in the pathogenesis of Kaposi´s sarcoma (KS) and some atypical B-cell lymphomas. The aim of this study was to investigate the influence of KSHV-infection on cellular gene expression in B-lymphocytes. In order to study the gene expression profile a microarray screen was performed using B-cells that have been persistently infected with KSHV in vitro. A considerable number of genes (408) were found to be modulated more than 4-fold by KSHV infection, 275 (67.4 %) were downregulated whereas 133 (32.6%) were upregulated. A multitude of the downregulated genes encoded for B-cell surface markers and several B-cell specific transcription factors (PAX-5, Oct-2 and Spi-B) which was confirmed by RT-PCR and on the protein level. The massive loss of B-cell surface markers or “null” phenotype, was similar to tumor cells isolated from primary effusion lymphoma (PEL). Thus, the loss of B-cell identity is due to KSHV-infection and not to cellular tumor-promoting events. Moreover, this study demonstrated that the “null” phenotype is caused by a soluble factor(s) released from KSHV-infected B-cells. The downregulation of B-cell markers led to severe functional defects, as KSHV-infected B-cells could not be activated by crosslinking of the B-cell receptor. Importantly, KSHV-infected cells could not be lysed by allo-reactive cytotoxic T-cells, suggesting that the “null” phenotype serves as a mechanism for immune escape.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 02/06
Since its first description in 1994 by Yuan Chang and Patrick Moore, Kaposi’s sarcoma-associated herpesvirus (KSHV) or Human Herpesvirus 8 (HHV-8) has emerged as a pathogen of international public health importance. It has been detected in biopsies of all forms of Kaposi’s sarcoma (KS), irrespective of geographic origin, age, or gender of the patient. Moreover, KSHV has been shown to be associated with two other diseases, multicentric Castleman’s disease (MCD) and primary effusion lymphoma (PEL). In comparison to alpha and beta-herpesvirinae, the understanding of KSHV-related pathogenesis has been hampered by inefficient virus replication in vitro, poor cell culture systems and the lack of an animal model. Thus, many basic questions concerning the biology of KSHV infection remain open. For example, the primary target cell of KSHV and the function of more than 50% of the viral proteins are still unknown. Since the investigation of viral gene functions by virus mutants did not prove to be very efficient for KSHV, a system for a genome-wide screening of viral gene functions by cloning the complete KSHV ORFeome (all open reading frames) and by generating KSHV arrays in a variety of different expression vectors was established in this project. Very often viruses regulate cellular signalling pathways, which favour viral infection and replication in the host cells. The SRE is a transcription factor binding site present in promoters of many genes involved in cell growth and transformation. In this study, a genome-wide screen for KSHV genes inducing the SRE element and AP-1 was performed. A strong induction of SRE by the latency-associated nuclear antigen 1 (LANA-1) was observed. LANA-1 is a multifunctional protein which interacts with the p53 and RB tumor suppressor proteins. This study reveals several novel functions of LANA-1. LANA-1 led to an activation of the ERK-1/2 MAP kinase, but also bound to the Mediator, a multi-subunit transcriptional coactivator complex for RNA polymerase II, via the ARC92/ACID1 subunit. Since LANA-1 interacted with SRF, one of the two transcription factors binding to the bipartite SRE element, a model for LANA-1 as an adaptor between specific transcription factors and the basal transcriptional machinery was hypothesized.
Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 01/06
Kaposi's Sarcoma Associated Herpesvirus (KSHV) or Human Herpesvirus-8 (HHV-8) is the most recently identified human gamma-2 herpesvirus and has been implicated in Kaposi's Sarcoma (KS) and primary effusion lymphoma (PEL). At the right end of the genome KSHV encodes the complex kaposin locus, which consists of two distinct sets of 23 amino acid direct repeats, DR2 and DR1, followed by a short domain originally referred to as open reading frame (ORF) K12. Translational initiation at multiple alternative CUG and one AUG start codons causes expression of a gradient of kaposin molecules with varying length and targeting motifs from one single transcript. The aim of the present study was to investigate in detail the expression pattern of the kaposin locus and the cellular localization and function of kaposin protein isoforms expressed in the KSHV+ PEL cell line BCBL-1. The multitude of translational products from all three reading frames could be resolved and different isoforms assigned to distinct cellular compartments. Depending on the alternative start codon used, the DR1 repeats representing a functional effector domain are fused either to the DR2 repeats harboring a nuclear localization sequence (NLS), or to K12, which encodes a transmembrane domain. Expression of kaposin in the nucleus (kaposin B) causes an activation of the AP-1 transcription factor and cellular promoters. The observed AP-1 induction is dependent on nuclear localization of both DR2 and DR1 repeats, since substitution of DR2 with a SV-40 NLS was not sufficient to restore activation. Other kaposin isoforms which are found in the cytosol (kaposin E) or membrane-associated (kaposin D) failed to activate AP-1. If co-expressed, however, kaposin D and E were able to modulate the kaposin B-caused induction, presumably mediated by a direct interaction between DR2 and DR1. The results presented in this study indicate a novel autoregulatory mechanism based on bidirectional targeting of a viral protein to distinct subcellular compartments by expression from different start codons and reading frames. Supported by the complexity of the translational program and the conservation of the repeat regions, these findings imply that kaposin isoforms have important functions in the viral life cycle.