About: Comprehensive Interactome Analysis Reveals that STT3B Is Required for N-Glycosylation of Lassa Virus Glycoprotein

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Comprehensive Interactome Analysis Reveals that STT3B Is Required for N-Glycosylation of Lassa Virus Glycoprotein
Creator	Pan, Xiaoyan Shang, Weijuan Wan, Weiwei Xiao, Gengfu Zhang, Lei-Ke Zhang, Yanjun Zhu, Shenglin
Source	PMC
abstract	Lassa virus (LASV) is the causative agent of a fatal hemorrhagic fever in humans. The glycoprotein (GP) of LASV mediates viral entry into host cells, and correct processing and modification of GP by host factors is a prerequisite for virus replication. Here, using an affinity purification-coupled mass spectrometry (AP-MS) strategy, 591 host proteins were identified as interactors of LASV GP. Gene ontology analysis was performed to functionally annotate these proteins, and the oligosaccharyltransferase (OST) complex was highly enriched. Functional studies conducted by using CRISPR-Cas9-mediated knockouts showed that STT3A and STT3B, the two catalytically active isoforms of the OST complex, are essential for the propagation of the recombinant arenavirus rLCMV/LASV glycoprotein precursor, mainly via affecting virus infectivity. Knockout of STT3B, but not STT3A, caused hypoglycosylation of LASV GP, indicating a preferential requirement of LASV for the STT3B-OST isoform. Furthermore, double knockout of magnesium transporter 1 (MAGT1) and tumor suppressor candidate 3 (TUSC3), two specific subunits of STT3B-OST, also caused hypoglycosylation of LASV GP and affected virus propagation. Site-directed mutagenesis analysis revealed that the oxidoreductase CXXC active-site motif of MAGT1 or TUSC3 is essential for the glycosylation of LASV GP. NGI-1, a small-molecule OST inhibitor, can effectively reduce virus infectivity without affecting cell viability. The STT3B-dependent N-glycosylation of GP is conserved among other arenaviruses, including both the Old World and New World groups. Our study provided a systematic view of LASV GP-host interactions and revealed the preferential requirement of STT3B for LASV GP N-glycosylation. IMPORTANCE Glycoproteins play vital roles in the arenavirus life cycle by facilitating virus entry and participating in the virus budding process. N-glycosylation of GPs is responsible for their proper functioning; however, little is known about the host factors on which the virus depends for this process. In this study, a comprehensive LASV GP interactome was characterized, and further study revealed that STT3B-dependent N-glycosylation was preferentially required by arenavirus GPs and critical for virus infectivity. The two specific thioredoxin subunits of STT3B-OST MAGT1 and TUSC3 were found to be essential for the N-glycosylation of viral GP. NGI-1, a small-molecule inhibitor of OST, also showed a robust inhibitory effect on arenavirus. Our study provides new insights into LASV GP-host interactions and extends the potential targets for the development of novel therapeutics against Lassa fever in the future.
has issue date	2019-11-13(xsd:dateTime)
bibo:doi	10.1128/jvi.01443-19
bibo:pmid	31511384
has license	cc-by
sha1sum (hex)	b75e7f3f923023185daed6f29e5beca4eddfc109
schema:url	https://doi.org/10.1128/jvi.01443-19
resource representing a document's title	Comprehensive Interactome Analysis Reveals that STT3B Is Required for N-Glycosylation of Lassa Virus Glycoprotein
has PubMed Central identifier	PMC6854512
has PubMed identifier	31511384
schema:publication	J Virol
resource representing a document's body	covid:b75e7f3f923023185daed6f29e5beca4eddfc109#body_text
is schema:about of	named entity 'OST' named entity 'performed' named entity 'revealed' named entity 'depends' named entity 'hemorrhagic fever' named entity 'subunits' named entity 'essential' named entity 'play' named entity 'inhibitor' named entity 'fatal' named entity 'GPs' named entity 'reduce' named entity 'Lassa fever' covid:arg/b75e7f3f923023185daed6f29e5beca4eddfc109 named entity 'CRISPR-Cas9' named entity 'interactions' named entity 'virus' named entity 'Our' named entity 'Old World' named entity 'Site-directed mutagenesis' named entity 'knockout' named entity 'essential' named entity 'viability' named entity 'participating' named entity 'vital' named entity 'study' named entity 'active' named entity 'infectivity' named entity 'N-glycosylation' named entity 'arenavirus' named entity 'mass spectrometry' named entity 'conserved' named entity 'critical' named entity 'interactions' named entity 'process' named entity 'isoforms' named entity 'mediated' named entity 'process' named entity 'targets' named entity 'complex' named entity 'arenavirus' named entity 'glycosylation' named entity 'N-glycosylation' named entity 'viral entry' named entity 'mass spectrometry' named entity 'oxidoreductase' named entity 'N-glycosylation' named entity 'isoforms' named entity 'infectivity' named entity 'STT3A' named entity 'arenavirus' named entity 'viral entry' named entity 'Lassa virus' named entity 'virus' named entity 'STT3A' named entity 'arenavirus' named entity 'virus' named entity 'active-site' named entity 'recombinant' named entity 'glycosylation' named entity 'MAGT1' named entity 'causative agent' named entity 'interactome' named entity 'Glycoprotein' named entity 'oligosaccharyltransferase' named entity 'preferential' named entity 'cell death' named entity 'FDR' named entity 'VSV' named entity 'significant effect' named entity 'STT3A' named entity 'glycosylation' named entity 'RNA' named entity 'STT3A' named entity 'virus infection'

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