Podcasts about herpesviruses

Clustered regularly interspaced short palindromic repeats (CRISPR-Cas12a), discovered a few years ago, is a method that detects even small levels of pathogens.Professor Kevin J Zwezdaryk and researchers at the Tulane University School of Medicine, USA, are working on a cost-effective, CRISPR-Cas12a-based pathogen detection tool aiming to upgrade patient care. Read more in Research Features Read the original research: doi.org/10.1016/j.bmt.2023.03.004

In this research summary we look at the role of reactivated human herpesviruses (HHV) in ME/CFS and Long Covid. This is because a number of recent studies have implied that HHV's could be involved in disease pathology causing and perpetuating symptoms. And because this might lead to effective treatments and diagnostic tests. 

Ten years and 8 autoimmune/chronic conditions into remission ago (in my Gettysburg address voice) I can tell you there is SO MUCH misinformation when it comes to autoimmune disease. So much that sometimes it makes me so angry with the medical profession.    Even our medical professionals don't readily share the truth about your body's ability to heal because they simply have been taught a different rhetoric.    Let's reprogram your rhetoric right here, right now, with the fact- filled research.   FREE One Day Detox https://www.inspirehealthbyjen.com/onedaydetox  Bloghttps://www.inspirehealthbyjen.com/work-with-jen    Alvergne, A., & Lummaa, V. (2010). Does the contraceptive pill alter mate choice in humans? Trends in Ecology & Evolution, 25(3), 171–179. https://doi.org/10.1016/j.tree.2009.08.003    Ascherio, A., & Munger, K. L. (2015). EBV and Autoimmunity. Current topics in microbiology and immunology, 390(Pt 1), 365–385. https://doi.org/10.1007/978-3-319-22822-8_15   Benagiano, G., Benagiano, M., Bianchi, P., D'Elios, M. M., & Brosens, I. (2019). Contraception in autoimmune diseases. Best practice & research. Clinical obstetrics & gynaecology, 60, 111–123. https://doi.org/10.1016/j.bpobgyn.2019.05.003   Bookwalter, D. B., Roenfeldt, K. A., LeardMann, C. A., Kong, S. Y., Riddle, M. S., & Rull, R. P. (2020). Posttraumatic stress disorder and risk of selected autoimmune diseases among US military personnel. BMC Psychiatry, 20(1), 1–8. https://doi.org/10.1186/s12888-020-2432-9   Dube SR, Fairweather D, Pearson WS, Felitti VJ, Anda RF, Croft JB, Dube, S. R., Fairweather, D., Pearson, W. S., Felitti, V. J., Anda, R. F., & Croft, J. B. (2009). Cumulative childhood stress and autoimmune diseases in adults. Psychosomatic Medicine, 71(2), 243–250. https://doi.org/10.1097/PSY.0b013e3181907888   FELDMAN, R. (2020). Perverse Incentives: Why Everyone Prefers High Drug Prices--Except for Those Who Pay the Bills. Harvard Journal on Legislation, 57(2), 303–376.   Houen, G., Trier, N. H., & Frederiksen, J. L. (2020). Epstein-Barr Virus and Multiple Sclerosis. Frontiers in immunology, 11, 587078. https://doi.org/10.3389/fimmu.2020.587078   Leverone, D., & Epstein, B. J. (2010). Nonpharmacological interventions for the treatment of rheumatoid arthritis: a focus on mind-body medicine. Journal of pharmacy practice, 23(2), 101–109. https://doi.org/10.1177/0897190009360025   Macarenco, M.-M., Opariuc-Dan, C., & Nedelcea, C. (2021). Childhood trauma, dissociation, alexithymia, and anger in people with autoimmune diseases: A mediation model. Child Abuse & Neglect, 122. https://doi.org/10.1016/j.chiabu.2021.105322   Mirashrafi, S., Hejazi Taghanaki, S. Z., Sarlak, F., Moravejolahkami, A. R., Hojjati Kermani, M. A., & Haratian, M. (2021). Effect of probiotics supplementation on disease progression, depression, general health, and anthropometric measurements in relapsing-remitting multiple sclerosis patients: A systematic review and meta-analysis of clinical trials. International Journal of Clinical Practice, 75(11), e14724. https://doi.org/10.1111/ijcp.14724 Posnett D. N. (2008). Herpesviruses and autoimmunity. Current opinion in investigational drugs (London, England : 2000), 9(5), 505–514.   Rashidian, A., Omidvari, A. H., Vali, Y., Sturm, H., & Oxman, A. D. (2015). Pharmaceutical policies: effects of financial incentives for prescribers. The Cochrane database of systematic reviews, 2015(8), CD006731. https://doi.org/10.1002/14651858.CD006731.pub2   Roberts, A. L., Malspeis, S., Kubzansky, L. D., Feldman, C. H., Chang, S. C., Koenen, K. C., & Costenbader, K. H. (2017). Association of Trauma and Posttraumatic Stress Disorder With Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women. Arthritis & rheumatology (Hoboken, N.J.), 69(11), 2162–2169. https://doi.org/10.1002/art.40222   Williams W. V. (2017). Hormonal contraception and the development of autoimmunity: A review of the literature. The Linacre quarterly, 84(3), 275–295. https://doi.org/10.1080/00243639.2017.1360065 https://www.nih.gov/news-events/nih-research-matters/epstein-barr-virus-autoimmune-diseases

Interview with Upstate virologist Eain Murphy, PhD

El mundo microscópico no deja de sorprendernos: esta semana hemos aprendido que los virus del herpes son capaces de "secuestrar" proteínas de transporte del interior de las células, llevárselas a otras células y usarlas allí para llegar adonde necesitan llegar. El periplo del herpes por nuestro cuerpo es muy complejo, y gracias a esa sofisticación los virus logran sobrevivir en nuestro interior durante toda la vida. En este episodio os contamos cómo el herpes entra en nuestro cuerpo a través de la piel y después "se esconde" en el interior de las neuronas. Pero las neuronas son células muy largas, a veces de más de un metro de largo, y para moverse por dentro de ellas necesitan "ir de polizones" en el propio transporte interno de la célula. La novedad de esta semana es que no sólo se aprovechan de las proteínas de transporte neuronales, sino que también secuestran otras proteínas de células de la piel para usarlas en el interior de la neurona. En el episodio de hoy os hablamos del ingenio y la sofisticación de estos virus, perfectamente adaptados para vivir entre nosotros. El artículo en que nos hemos basado es "Herpesviruses assimilate kinesin to produce motorized viral particles", de Caitlin Pegg et al. Nature, vol. 599 (2021). Podéis encontrarlo en este enlace: https://www.nature.com/articles/s41586-021-04106-w Durante el programa mencionamos un programa anterior en el que hablamos de otra interacción peculiar entre neuronas y virus, en este caso en la otra dirección: neuronas que "domestican" virus para usarlos como mensajeros. Si lo queréis escuchar, es el episodio s07e22. También hablamos de otro episodio en el que viajamos al interior de la célula y describimos cómo es por dentro: es el capítulo s10e04. Y finalmente, si queréis aprender más sobre el "transporte de mercancías" en el interior de las células buscad el episodio s03e04. Este programa se emitió originalmente el 26 de noviembre de 2021. Podéis escuchar el resto de audios de La Brújula en la app de Onda Cero y en su web, ondacero.es

This week Jack is joined by Professor Thomas Schulz to hear about the Kaposi's sarcoma-associated herpesvirus, the most common cause of tumours in men in sub-Saharan Africa, and how herpesviruses mask themselves from our immune systems. If you like this podcast check out some of our previous content about herpesviruses over at cvrblogs.myportfolio.com. Music: The Zeppelin by Blue Dot Sessions (http://freemusicarchive.org/music/Blue_Dot_Sessions/Aeronaut/The_Zeppelin_1908)

Investigating and assigning gene functions of herpesviruses is a process, which profits from consistent technical innovation. Cloning of bacterial artificial chromosomes encoding herpesvirus genomes permits nearly unlimited possibilities in the construction of genetically modified viruses. Targeted or randomized screening approaches allow rapid identification of essential viral proteins. Nevertheless, mapping of essential genes reveals only limited insight into function. The usage of dominant-negative (DN) proteins has been the tool of choice to dissect functions of proteins during the viral life cycle. DN proteins also facilitate the analysis of host-virus interactions. Finally, DNs serve as starting-point for design of new antiviral strategies.

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.

Vincent, DIck, and Alan chat about reconstruction of a bat SARS-like coronavirus, herpesviruses that are killing elephants in zoos, and a plan to eradicate AIDS in ten years. Links for this episode: The Virology Network at socialmedian.com. The bat SARS-like coronavirus: scientific article in PNAS, and the Wired Science article. NY Times Editorial on eradicating AIDS. Herpesviruses killing elephants. Science podcast pick of the week: Futures in Biotech. Science book of the week: Principles of Molecular Virology, by AJ Cann.

Host: Vincent Racaniello Special guest: Saul Silverstein Dickson Despommier is away this week at Pop!Tech. CDC pages on herpes and zoster (shingles).

Human cytomegalovirus is a ubiquitous human pathogen, causing disease in the immunocompromised host. Most of its ORFs have not been well studied due to a limited host range and slow growth of HCMV in cultured cells. MCMV, a natural pathogen isolated from mice, constitutes the most amenable animal model for human β-herpesviruses. To date most of its approximately 200 genes have an unknown function. For the analysis of these genes straightforward mutagenesis methods are necessary. With the cloning of herpesviruses as an infectious bacterial artificial chromosome a novel approach of mutagenesis has been established. Herpesviruses are now accessible to the tools of bacterial genetics. Since then site-directed mutagenesis by homologous recombination using linear DNA fragments and random transposon BAC mutagenesis have been introduced to delineate the functions of viral ORFs. The purpose of this work was to analyze two members of the US 22 gene homolog family, genes m139 and m142, with site-directed mutagenesis. Members of this family are conserved in all herpesviruses and mostly have unknown functions. Transposon mutants showed a macrophage phenotype for m139, whereas m142 was possibly essential for viral replication. Genes m139-m141 and m142-m143 have complex transcriptional regions and have 3´-coterminal transcripts. The insertion of a 3-kb large transposon could destabilize the upstream transcripts. Site-directed mutants of genes m139 and m142, where only the start codon is deleted, should not influence transcript stability and permit confirmation of the results obtained with transposon mutagenesis. Targeted mutants of MCMV BAC were constructed for ORF m139 (ΔATG-m139) and m142 (ΔATG-m142, ΔATG-m142/FRT) by homologous recombination using linear DNA fragments. Mutant ΔATG-m139 showed attenuated growth in peritoneal macrophages. This mutant, with the first two ATGs deleted, expressed a truncated protein of 61 kDa. Gene m139 seems to act in cooperation with genes m140 and m141 on the protein level. The site-directed MCMV BAC mutant of ORF m142 on the other hand could not reconstitute viral progeny in eukaryotic cells. The ORF of m142 was inserted an ectopic position and viral progeny was reconstituted with this revertant. Thus, it was shown that gene m142 is essential for viral replication. Further analysis of nonessential and essential genes of cytomegalovirus will be needed to understand CMV viral pathology and to develop vaccines for herpesvirus infection and vectors for gene therapy.

Herpesviruses cause highly prevalent infections associated with usually mild symptoms resulting in life long latency. However, they can provoke fatal disease in susceptible individuals such as immunocompromised patients either in the context of primary infection or after reactivation from latency. Despite of their emerging medical importance, herpesvirus infections can so far only be controlled by antiviral therapy targeting viral DNA replication, accompanied with side effects and occurrence of resistant strains. In this work, a novel platform for drug discovery was established that is based on a protein complementation assay (PCA), which can be used to study viral protein-protein interactions in a simple cell based assay. In a PCA two inactive fragments of a reporter enzyme are fused to two interacting proteins. Interaction of the proteins leads to proximity of the enzyme fragments, followed by reconstitution of the reporter enzyme activity. Members of the UL34 and UL31 families are conserved herpesvirus proteins. They interact with one another forming the nuclear egress complex (NEC), which is essential for the export of viral capsids from the cell nucleus. This crucial protein-protein interaction might serve as a potential drug target for anti-herpesvirus chemotherapy. In this work the mutual binding sites of the two proteins were localized and studied for their conservation. A PCA was established for M50 and M53 – the NEC proteins of the murine cytomegalovirus (MCMV) - by fusion of the N- and C-terminal part of the TEM-1 ß-lactamase of E. coli. The assay was validated and applied to representative members of the three herpesvirus subfamilies. Cross-complementation assays showed that partners derived from the same subfamily can replace each other in the PCA, however, homologues from different subfamilies can not. This cross-complementation reflects the in vivo situation: the human cytomegalovirus (HCMV), but not the HSV-1 or PrV homologues are able to rescue the M50 or M53 null phenotype in the viral context of MCMV. The lack of complementation between the subfamilies is due to their diverged binding sites, which are located in all cases within the first conserved region of the UL31 family proteins. The study of the binding site in UL34 family members revealed a bipartite binding motif. With the aim of a future high-throughput inhibitor screen an in vitro NEC-PCA was established using purified fusion proteins of HCMV.