Recognition of Reovirus RNAs by the Innate Immune System

Abstract

Mammalian orthoreovirus (reovirus) is a dsRNA virus, which has long been used as a model system to study host-virus interactions. One of the earliest interactions during virus infection is the detection of the viral genomic material, and the consequent induction of an interferon (IFN) based antiviral response. Similar to the replication of related dsRNA viruses, the genomic material of reovirus is thought to remain protected by viral structural proteins throughout infection. Thus, how innate immune sensor proteins gain access to the viral genomic material, is incompletely understood. This review summarizes currently known information about the innate immune recognition of the reovirus genomic material. Using this information, we propose hypotheses about host detection of reovirus.

Keywords: dsRNA; innate immunity; interferon; reovirus; sensing.

Figure 1

Reovirus replication cycle.

Figure 2

Reovirus virions enter host cells through receptor-mediated endocytosis. We propose potential fates for incoming virions that reach host endosomes. (A) Particles undergo disassembly within endosomes, which mediates pore formation in the endosome for the deposition of transcriptionally active cores to initiate replication. (B) A proportion of the particles may be unable to exit endosomes properly, where they are degraded to release genomic RNA. (C) Partially degraded particles enter the cytoplasm where they fall apart. (D) Intact cores are deposited into the cytoplasm, but later fall apart or are degraded by the host. In B–D, reovirus genomic RNA is made available to the host for sensing by RIG-I-like receptors (RLRs) and the subsequent induction of infectious subvirion particles (ISVP). Each of these possibilities could happen within the same cell, such that the virus can both establish infection and be sensed.