Mammalian Orthoreovirus Biology and Pathogenesis

Mammalian orthoreoviruses are non-enveloped, double-stranded RNA viruses with a segmented genome encapsidated within concentric icosahedral protein shells. The outer capsid contains an attachment protein, σ1, which mediates initial engagement with host cell glycans and protein receptors, followed by internalisation and uncoating within endosomes. Genome segments encode structural proteins required for virion assembly and non-structural proteins that regulate viral transcription and host innate responses. Infection typically begins in the intestinal or respiratory epithelium, with dissemination to secondary sites determined by serotype-specific receptor usage and capsid conformational changes. In many mammals, orthoreovirus species cause largely subclinical or mild enteric and respiratory disease, but certain strains can invade the central nervous system, producing neurological syndromes in susceptible hosts. Genetic reassortment among strains from different animal reservoirs underlies host-range expansion and emergence of novel variants. Interaction with the microbiota and host immune factors modulates thermostability of viral particles and influences both transmission and tropism. Beyond their medical significance, orthoreoviruses serve as valuable models for understanding receptor binding, membrane penetration and antiviral immunity, and are under investigation as oncolytic agents and vaccine vectors. Global surveillance of zoonotic strains and mechanistic study of receptor engagement remain priorities for predicting and mitigating reovirus-associated disease.

Research from Nature Portfolio

Recent studies have identified paired immunoglobulin-like receptor B (PirB) as a high-affinity entry receptor for neurotropic orthoreovirus serotype 3 in murine cortical neurons. Binding to PirB via its extracellular D3D4 domains facilitates receptor-mediated signalling that accelerates clathrin-dependent endocytosis and enhances viral replication in the brain, establishing a molecular basis for serotype-dependent neuropathogenesis. Complementary work using atomic force microscopy has revealed that initial attachment of the σ1 trimer to cell-surface sialic acid triggers a conformational rearrangement of σ1, promoting multivalent engagement of junctional adhesion molecule A (JAM-A). This stepwise receptor engagement model unifies glycan and protein receptor interactions, clarifying how conformational dynamics of the attachment fibre govern tropism and infectivity.

Mammalian Orthoreovirus Biology and Pathogenesis publication trend

The graph below shows the total number of articles in mammalian orthoreovirus biology and pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

σ1 attachment protein: A trimeric fibre projecting from the viral capsid that binds cell-surface glycans and protein receptors to initiate entry.

Infectious subvirion particle (ISVP): A partially uncoated form of the virion generated during early endosomal processing, primed for membrane penetration.

Paired immunoglobulin-like receptor B (PirB): A host immune receptor that, when engaged by viral σ1, triggers signalling facilitating orthoreovirus internalisation.

Heparan sulphate: A ubiquitous cell-surface glycosaminoglycan that can function as an attachment receptor for multiple orthoreovirus variants.

Genetic reassortment: The exchange of genome segments between co-infecting orthoreovirus strains, generating novel progeny with mixed gene constellations.

Thermostability: The ability of a viral particle to retain infectivity under varying temperature and environmental stresses, often enhanced by interactions with microbial components.

References

1. Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus. Nature Communications (2023).
2. Pteropine orthoreoviruses use cell surface heparan sulphate as an attachment receptor. Emerging Microbes & Infections (2023).
3. Isolation and identification of a novel porcine-related recombinant mammalian orthoreovirus type 3 strain from cattle in Guangxi Province, China. Frontiers in Microbiology (2024).
4. Bacteria and bacterial envelope components enhance mammalian reovirus thermostability. PLOS Pathogens (2017).
5. Glycan-mediated enhancement of reovirus receptor binding. Nature Communications (2019).