Comprehensive interactome analysis of the spike protein of swine acute diarrhea syndrome coronavirus

Abstract

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently discovered coronavirus that causes severe and acute diarrhea and rapid weight loss in piglets. SADS-CoV was reported to be capable of infecting cell lines derived from diverse species, including bats, mice, hamsters, rats, chickens, pigs, nonhuman primates, and humans, implying its high risk of cross-species infection. However, its receptor is still unknown. In this study, the receptor-binding domain of the SADS-CoV spike (S) protein was purified and then subjected to affinity purification (AP)-coupled mass spectrometry (MS)-based proteomic analysis to identify the interactors of the SADS-CoV S protein. Forty-three host proteins were identified, and a Gene Ontology analysis indicated that these interactors can be grouped into categories such as “cell-cell adhesion”, “translation” “viral transcription”, suggesting that these processes may participate in the SADS-CoV life cycles. RNA interference-based screening of these interactors indicated that PPIB and vimentin can affect SADS-CoV replication. Our study provides an overarching view into the host interactome of the SADS-CoV S protein and highlights potential targets for the development of therapeutics against SADS-CoV.

Research Advances on Swine Acute Diarrhea Syndrome Coronavirus

“…Furin protease is responsible for hydrolyzing the S1/S2 cleavage site and the 97 aa cleavage site upstream of it in the SADS-CoV S protein, and this process is necessary for viral S protein-mediated cell-cell fusion [133]. In addition, peptidylprolyl isomerase B (PPIB), a member of the proline isomerase family, binds to the receptor-binding domain of the SADS-CoV S protein [134]. Vimentin interacts with the SADS-CoV S1 subunit, contributing to essential cellular processes such as cell division and migration [135].…”

“…Vimentin interacts with the SADS-CoV S1 subunit, contributing to essential cellular processes such as cell division and migration [135]. A reduction in PPIB and vimentin expression induced by RNA interference significantly inhibited the replication of SADS-CoV [134]. However, the detailed mechanisms of action of these two key host factors remain unknown [134].…”

“…A reduction in PPIB and vimentin expression induced by RNA interference significantly inhibited the replication of SADS-CoV [134]. However, the detailed mechanisms of action of these two key host factors remain unknown [134]. Bile acids (BAs) play an important role in viral invasion [136].…”