Comprehensive mapping of rhadinovirus dissemination and persistence

点击翻译按钮获取中文摘要

Rhadinoviruses infect both man and economically important animals. Infection predisposes to several cancers, and even though these are individually uncommon the high prevalence of infection leads to a large total disease burden, particularly in the developing world. For example Kaposi's Sarcoma is the commonest cancer in untreated HIV infection and is caused by a rhadinovirus. Once rhadinoviruses infect they persist lifelong and spread to close contacts. However, surprisingly little is known about how and where in the body they persist. White blood cells are one site but there also appear to be other sites that are important for disease. The lack of complete information makes it very difficult to develop infection control measures such as vaccination. Large animal and human rhadinoviruses are difficult to study. However, all mammals carry their own related viruses that behave in broadly similar ways. Mice provide the standard experimental model of mammalian biology, and so by studying a murine rhadinovirus - MuHV-4 - we can go a long way to understanding how these viruses as a whole work. Here we will use MuHV-4 to establish where in the body persistent infection is established, how it gets there from the point of virus entry, and how it then gets back to the sites from which virus is released to infect new hosts. Rhadinoviruses can exist in either lytic or latent forms. When lytic they produce new virus, but are vulnerable to attack; when latent they are relatively inactive and so difficult to attack. Persistent infection is predominantly latent. However, lytic replication is required for virus to spread between different cell types, and this seems to be essential for normal infection. By defining precisely where lytic replication is essential we can identify targets for therapeutic intervention. Thus we can start to develop new means of reducing human and animal disease.