Virus-host interplay-Immediate virus recognition by RIG-I and PKR and viral counterstrategies

Michaela Gerlach, Weber, Friedemann (Prof. Dr.), Medizin
Viruses are a constant threat to mankind causing diseases ranging from mild symptoms to fatal outcome. A rapid and efficient antiviral response is therefore crucial for the survival of the host. RIG-I-like receptors (RLR) and other immune receptors, like protein kinase R (PKR), specifically detect viral RNA species in the host cytoplasm. The sensing of virus infection triggers intracellular defense mechanisms resulting in viral alertness in the infected and surrounding cells, and forms the link
more » ... and forms the link to the adaptive immune system. Viruses, in turn, have evolved sophisticated countermeasures to dampen the antiviral response. The molecular mechanisms involved range from a broad shut-off of the host cell metabolism to a sensitive interference with key components of the immune system. For a better understanding, which viral RNA structures are detected by immune receptors like RIG-I and PKR and what kind of viral antagonists lead to their inhibition, it is crucial to be able to determine their activation status. Hence, limited protease digestion and native polyacrylamide gel electrophoresis (PAGE) were established to directly monitor RIG-I and PKR conformational switching and oligomerization upon activation, respectively. Various studies helped to identify RIG-I stimulating RNA structures in vitro, but the first viral structure triggering an antiviral interferon response in the natural context of virus infection remained to be resolved. We identified 5triphosphorylated (5ppp) panhandle structures packaged into nucleocapsids as physiological RIG-I agonists. Independent of virus transcription and replication, the incoming encapsidated genomes of bunyaviruses (La Crosse virus; LACV and Rift Valley fever virus; RVFV) and orthomyxovirus (influenza A virus; FLUAV) were able to stimulate RIG-I activation and an antiviral signaling cascade. Su [...]
doi:10.17192/z2015.0159 fatcat:wbd4rc5wybdnvnapbwhasqydfe