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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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC8127515 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Wang Qingxing Q Luo Yun Y Shang Weijuan W Shi Zhengli Z Xiao Gengfu G Zhang Leike L

Biosafety and health 20210517 3

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) pro ...[more]

PMID: 34027383

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Project description:Bats are reservoirs for diverse coronaviruses, including swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV was first identified in diarrheal piglets in 2017. As a novel alphacoronavirus, SADS-CoV shares ~95% identity with bat alphacoronavirus HKU2. SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. Thus far, no effective antiviral drugs or vaccines are available to treat infections with SADS-CoV. Therefore, knowledge of the protein-coding gene set and a subcellular localization map of SADS-CoV proteins are fundamental first steps in this endeavor. Here, all SADS-CoV genes were cloned separately into Flag-tagged plasmids, and the subcellular localizations of viral proteins, with the exception of nsp11, were detected using confocal microscopy techniques. As a result, nsp1, nsp3-N, nsp4, nsp5, nsp7, nsp8, nsp9, nsp10, nsp14, and nsp15 were localized in the cytoplasm and nuclear spaces, and these viral proteins may perform specific functions in the nucleus. All structural and accessory proteins were mainly localized in the cytoplasm. NS7a and membrane protein M colocalized with the Golgi compartment, and they may regulate the assembly of SADS-CoV virions. Maturation of SADS-CoV may occur in the late endosomes, during which envelope protein E is involved in the assembly and release of the virus. In summary, the present study demonstrates for the first time the location of all the viral proteins of SADS-CoV. These fundamental studies of SADS-CoV will promote studies of basic virology of SADS-CoV and support preventive strategies for animals with infection of SADS-CoV. IMPORTANCE SADS-CoV is the first documented spillover of a bat coronavirus that causes severe diseases in domestic animals. Our study is an in-depth annotation of the newly discovered swine coronavirus SADS-CoV genome and viral protein expression. Systematic subcellular localization of SADS-CoV proteins can have dramatic significance in revealing viral protein biological functions in the subcellular locations. Furthermore, our study promote understanding the fundamental science behind the novel swine coronavirus to pave the way for treatments and cures.

Project description:Coronaviruses (CoV) have caused a number of major epidemics in humans and animals, including the current pandemic of coronavirus disease 2019 (COVID-19), which has brought a renewed focus on the evolution and interspecies transmission of coronaviruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), which was recently identified in piglets in southern China, is an alphacoronavirus that originates from the same genus of horseshoe bats as severe acute respiratory syndrome CoV (SARS-CoV) and that was reported to be capable of infecting cells from a broad range of species, suggesting a considerable potential for interspecies transmission. Given the importance of the coronavirus spike (S) glycoprotein in host range determination and viral entry, we report a cryo-electron microscopy (cryo-EM) structure of the SADS-CoV S trimer in the prefusion conformation at a 3.55-Å resolution. Our structure reveals that the SADS-CoV S trimer assumes an intrasubunit quaternary packing mode in which the S1 subunit N-terminal domain (S1-NTD) and the S1 subunit C-terminal domain (S1-CTD) of the same protomer pack together by facing each other in the lying-down state. SADS-CoV S has several distinctive structural features that may facilitate immune escape, such as a relatively compact architecture of the S trimer and epitope masking by glycan shielding. Comparison of SADS-CoV S with the spike proteins of the other coronavirus genera suggested that the structural features of SADS-CoV S are evolutionarily related to those of the spike proteins of the other genera rather than to the spike protein of a typical alphacoronavirus. These data provide new insights into the evolutionary relationship between spike glycoproteins of SADS-CoV and those of other coronaviruses and extend our understanding of their structural and functional diversity.IMPORTANCE In this article, we report the atomic-resolution prefusion structure of the spike protein from swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV is a pathogenic alphacoronavirus that was responsible for a large-scale outbreak of fatal disease in pigs and that was reported to be capable of interspecies transmission. We describe the overall structure of the SADS-CoV spike protein and conducted a detailed analysis of its main structural elements. Our results and analyses are consistent with those of previous phylogenetic studies and suggest that the SADS-CoV spike protein is evolutionarily related to the spike proteins of betacoronaviruses, with a strong similarity in S1-NTDs and a marked divergence in S1-CTDs. Moreover, we discuss the possible immune evasion strategies used by the SADS-CoV spike protein. Our study provides insights into the structure and immune evasion strategies of the SADS-CoV spike protein and broadens the understanding of the evolutionary relationships between coronavirus spike proteins of different genera.

Dataset Information

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

Publications

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

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