How infectious SARS-CoV-2 exploits two ER membrane proteins to promote infection

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Billy  Tsai
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2024
Award: $381,397
Funding agency: National Institute of Allergy and Infectious Diseases

Abstract
SARS-CoV-2 exploits the function of the endoplasmic reticulum (ER) to promote its
infection life cycle. Despite its strong reliance on the ER, the molecular basis by which
SARS-CoV-2 hijacks ER factors to promote defined steps of this life cycle remains
unclear. Using infectious SARS-CoV-2, we recently identified two ER membrane
proteins – RTN3 and SigmaR1 – as critical host factors that support virus infection. Our
findings further reveal that RTN3 plays a role in viral replication, while SigmaR1 exerts a
function in viral secretion. However, how SARS-CoV-2 exploits the activities of RTN3
and SigmaR1 to accomplish these two distinct tasks, in mechanistic terms, is completely
unknown. Accordingly, the objective of this application is to elucidate the molecular basis
by which these two ER membrane factors promote replication and secretion of SARS-
CoV-2. We believe these insights will not only illuminate the basic infection mechanism
of SARS-CoV-2, but given the continuing global COVID-19 pandemic, may lead to the
development of effective anti-virals to blunt the devastating impact of SARS-CoV-2.

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