Persistent RNA virus infections: do PAMPS drive chronic disease?

Abstract

Chronic disease associated with persistent RNA virus infections represents a key public health concern. While human immunodeficiency virus-1 and hepatitis C virus are perhaps the most well-known examples of persistent RNA viruses that cause chronic disease, evidence suggests that many other RNA viruses, including re-emerging viruses such as chikungunya virus, Ebola virus and Zika virus, establish persistent infections. The mechanisms by which RNA viruses drive chronic disease are poorly understood. Here, we discuss how the persistence of viral RNA may drive chronic disease manifestations via the activation of RNA sensing pathways.

Figure 1. Tissues associated with RNA virus persistence

Several RNA viruses from diverse virus families persist in immune privileged body sites and tissues (green/blue boxes). The male reproductive tract has been shown to harbor persistent ZIKV and EBOV, contributing to continued transmission, and (in animal models of ZIKV) damaging tissue and potentially affecting fertility. EBOV and ZIKV also persist in ocular tissue, the latter thus far demonstrated in animal models. The CNS [brain and CSF] is a site for persistent WNV (only demonstrated in animal models) as well as EBOV and MeV. Other body tissues which are not considered prototypical immune privileged sites (orange boxes) are associated with persistence of various RNA viruses. HCV persists in the liver. The myocardium is a well-established site of persistence for enteroviruses. Viral RNA and antigen from the togaviruses CHIKV and Ross River virus persist in joint-associated tissue, and in animal models CHIKV has been shown to persist in lymphoid tissue. The kidney has been identified as a potential site of WNV persistence in animal models, although this remains a speculative site of persistence in humans. RNA from the paramyxoviruses MeV and RSV persists in the respiratory tract.