Epstein Barr Virus and HHV-8), but it is hoped the reader through this small selection will get a flavour of the complex hostvirus interactions which are being unpicked by researchers around the world, and some of the methods being used to develop new diagnostic and prognostic tools, treatments and vaccines. Although the viruses are very different genetically and indeed the diseases are clinically diverse, there are some shared elements of pathogenesis which link them together. researchers around the world, and some of the methods being used to develop new diagnostic and prognostic tools, treatments and vaccines. Although the viruses are very different genetically and indeed the diseases are clinically diverse, there are some shared elements of pathogenesis which link them together. Four are highlighted below: Much of the tissue damage in such infections may be host Rabbit polyclonal to FDXR mediated: although viruses may cause direct cytopathic effects, it is also clear PROTAC FAK degrader 1 that in chronic hepatitis, immune-mediated damage to the liver is a major player. This is particularly obvious in hepatitis B infection. Even in HIV, where there is relative immunodeficiency, immune activation may contribute to the progression towards acquired immuno-deficiency syndrome (AIDS), and there is an important immunopathology associated with viral encephalitides. The focus of many researchers is subtly shifting from adaptive mechanisms towards innate immunity: it is clear that adaptive responses such as antibody and T cells play a huge role in containment of persistent infections. However, to understand the differential outcomes of infection, a better definition of the innate response is required. This is very obvious in PROTAC FAK degrader 1 the case of hepatitis C, where host genetics points the finger at the interferon lambda geneIL28B(see accompanying review). Overall, the view that robust protective immunity is a team game for the immune system is clearly emerging. Low levels of virus in tissues are very hard to eliminate and provide a complex target for therapy: Hepatitis B virus, for example, is never fully eliminatedeven in those who have apparently cleared infectionand may reactivate during immunosuppression, e.g. with a B-cell depleting monoclonal antibody. CMV’s low-level persistence contributes to the massive expansion of virus-directed CD8+ T cells seen in the elderly. In the case of HIV, targeting the low levels of virus which remain even in the face of highly suppressive anti-retroviral therapies remains an important therapeutic goal. Viral evolutionary capacity will remain a major challenge PROTAC FAK degrader 1 for the future: although the viruses illustrated are from diverse families, in each case viral evolution can contribute to persistence and pathogenesis. This is especially obvious in the cases of HIV and HCV, where high levels of viremia are accompanied by huge intra-host viral diversificationa result of the error-prone nature of RNA and retroviral replication. However, even relatively stable viruses such as CMV develop resistance to drugsin vivoand indeed PROTAC FAK degrader 1 we are only starting to scratch the surface of the diversity of these large DNA viruses, using next-generation sequencing. Viral diversity provides a major challenge for vaccines against viruses with variable envelopes and also for drug development. Once again, a team approach, by targeting multiple pathways or sites within the virus should provide the key to effective vaccines and therapies. Developing a better understanding of these major virus infections requires attack from a variety of angles, including host genetics, viral genetics, cell biology, immunology and interventional clinical studies. The last decade has seen a massive transformation in the techniques used to study viral infections in man and a similar revolution in our understanding of pathogenesis. It is hoped that the next decade will produce similar advances in therapy and vaccines for these diverse and complex threats. == Funding == Wellcome Trust Fellowship awards (WT091663MA); NIHR Biomedical Research Centre (Oxford); The Oxford Martin School; National Institutes of Health (NIAID 1U19AI082630-01)..