Reovirus Core Proteins λ1 and σ2 Promote Stability of Disassembly Intermediates and Influence Early Replication Events.

The capsids of mammalian reovirus contain two concentric protein shells, the core and the outer capsid. The outer capsid is composed of μ1-σ3 heterohexamers which surround the core. The core is composed of λ1 decamers held in place by σ2. After entry into the endosome, σ3 is proteolytically degraded and μ1 is cleaved and exposed to form infectious subvirion particles (ISVPs). ISVPs undergo further conformational changes to form ISVP*s, resulting in the release of μ1 peptides, which facilitate the penetration of the endosomal membrane to release transcriptionally active core particles into the cytoplasm. Previous work identified regions or specific residues within reovirus outer capsid proteins that impact the efficiency of cell entry. We examined the functions of the core proteins λ1 and σ2. We generated a reovirus T3D reassortant that carries strain T1L-derived σ2 and λ1 proteins (T3D/T1L L3S2). This virus displays lower ISVP stability and therefore converts to ISVP*s more readily. To identify the molecular basis for lability of T3D/T1L L3S2, we screened for hyperstable mutants of T3D/T1L L3S2 and identified three point mutations in μ1 that stabilize ISVPs. Two of these mutations are located in the C-terminal ϕ region of μ1, which has not previously been implicated in controlling ISVP stability. Independent of compromised ISVP stability, we also found that T3D/T1L L3S2 launches replication more efficiently and produces higher yields in infected cells than T3D. In addition to identifying a new role for the core proteins in disassembly events, these data highlight the possibility that core proteins may influence multiple stages of infection.