From touchdown to transcription: the reovirus cell entry pathway

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Mammalian orthoreoviruses (reoviruses) are nonenveloped viruses with double-stranded RNA genomes.
• Reoviruses are model systems for studying virus-cell interactions, innate immunity, and disease.
• Reovirus entry involves binding to cell-surface carbohydrates and junctional adhesion molecule-A (JAM-A).

Purpose of the Study:

• To review the mechanisms of reovirus cell entry.
• To elucidate how reoviruses activate innate immune response signaling pathways.

Main Methods:

• The review synthesizes existing research on reovirus-host interactions.
• Focuses on molecular mechanisms of viral attachment, internalization, and cytoplasmic delivery.
• Examines the role of viral proteins (σ1, σ3, μ1) and host factors (JAM-A, β1 integrins, cathepsins).

Main Results:

• Reovirus attachment protein σ1 binds JAM-A by disrupting its homodimer.
• Internalization is mediated by β1 integrins, likely through clathrin-dependent endocytosis.
• Outer-capsid protein σ3 removal exposes μ1, which mediates endosomal membrane rupture and cytoplasmic delivery of the viral core.
• A μ1 cleavage fragment activates NF-κB and induces apoptosis.

Conclusions:

• Reovirus cell entry is a multi-step process involving specific viral-host protein interactions.
• Reovirus infection triggers innate immune responses, including NF-κB activation and apoptosis.
• Understanding these mechanisms provides insights into viral pathogenesis and potential therapeutic targets.