Abstract
Destabilization of a non-enveloped virus generates a membrane transport-competent viral particle. Here we probe polyomavirus SV40 endoplasmic reticulum (ER)-to-cytosol membrane transport, a decisive infection step where destabilization initiates this non-enveloped virus for membrane penetration. We find that a member of the ER membrane protein complex (EMC) called EMC1 promotes SV40 ER membrane transport and infection. Surprisingly, EMC1 does so by using its predicted transmembrane residue D961 to bind to and stabilize the membrane-embedded partially destabilized SV40, thereby preventing premature viral disassembly. EMC1-dependent stabilization enables SV40 to engage a cytosolic extraction complex that ejects the virus into the cytosol. Thus EMC1 acts as a molecular chaperone, bracing the destabilized SV40 in a transport-competent state. Our findings reveal the novel principle that coordinated destabilization-stabilization drives membrane transport of a non-enveloped virus.
Highlights
Viruses have evolved sophisticated strategies to penetrate biological membranes to gain entry into host cells and cause disease (Cosset and Lavillette, 2011; Greber, 2016; Luisoni et al, 2015; Dormitzer et al, 2004; Chandran et al, 2002)
The results identified potential C18 interacting partners (Figure 1A, silver stained gel), including an approximately 110 kDa protein called endoplasmic reticulum (ER) membrane protein complex subunit 1 (EMC1)
EMC1 is predicted to be a single-pass type I ER-resident transmembrane protein that is the largest component of a multiprotein complex called ER membrane protein complex (EMC), which consists of 10 proteins in humans (Christianson et al, 2012)
Summary
Viruses have evolved sophisticated strategies to penetrate biological membranes to gain entry into host cells and cause disease (Cosset and Lavillette, 2011; Greber, 2016; Luisoni et al, 2015; Dormitzer et al, 2004; Chandran et al, 2002). These results strongly suggest that EMC1 executes a specific function in promoting SV40 ER membrane penetration, consistent with its role in facilitating viral infection.
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