Viral persistence, liver disease, and host response in a hepatitis C–like virus rat model

Abstract

We developed RHV-rn1-infected rats as a fully immunocompetent and informative surrogate model to delineate the mechanisms of HCV-related viral persistence, immunity, and pathogenesis. (Hepatology 2018).

Evolutionary biology of human hepatitis viruses

“…mice and rats infected with rat hepaciviruses. 166 In contrast to these rodents, some bat species have a comparably long life span of up to 30 years. 167 However, whether bats can get chronically infected with hepaciviruses and if this infection leads to oncogenesis is unknown.…”

Of mice, rats, and men: Small animal model of hepatitis C virus infection

“…New doors in HCV animal modeling may now be opening. Two recent publications described experimental infection of mice and rats with a hepacivirus isolated from feral Norway rats ( Rattus norvegicus ) trapped in New York City. These small animal models will undoubtedly help to establish further understanding of the pathogenesis of hepaciviruses.…”

“…Like HCV, the rat virus is classified within the Hepacivirus genus of the Flavivirus family. Key characteristics it shares with HCV include genome organization, polyprotein cleavage sites, conserved 5′ and 3′ untranslated region (UTR) secondary structure, and functional microRNA‐122 (miR‐122) binding sites in the 5′ UTR critical for liver tropism . Mice and rats were immunocompetent and replication did not require expression of human entry factors in hepatocytes.…”

“…They include access to liver where the virus replicates, infection of genetically identical or modified rodents, and use of clonal hepaciviruses that can be mutated to identify structural features important for replication and immune evasion. Impaired infection in rats challenged with clonal hepaciviruses carrying mutations in the 5′ UTR miR‐122 seed sites demonstrates this principle . These models will almost certainly have some limitations, but they are difficult to predict given the preliminary characterization of infection and immunity.…”

A mouse model for hepatitis C virus infection: are we there yet?

“…Further, it is not known if quasispecies variation exists in NrHV-infected mice, and mice are not the natural host for NrHV thus requiring pre-depletion of CD4 + T cells to establish chronic infection. Recently, the same virus was reported to induce hepatitis and steatosis in chronically infected rats (21), but it remains unclear if this could serve tangibly as a model. Overall, NrHV infection of both mice and rats could be highly valuable in HCV research and may help fill the knowledge gap leading to a successful HCV vaccine.…”