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Article: HIV-1 envelope glycoprotein variable loops are indispensable for envelope structural integrity and virus entry

TitleHIV-1 envelope glycoprotein variable loops are indispensable for envelope structural integrity and virus entry
Authors
Issue Date2013
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2013, v. 8 n. 8, p. Article numbere 69789 How to Cite?
AbstractHIV-1 envelope (Env) glycoprotein is a trimer of heterodimer of gp120 and gp41, and derives from a trimeric glycoprotein precursor, gp160. Gp120 contains five conserved regions that are interspersed with 5 variable loop regions (V1-V5). Env variations in variable loop length and amino acid composition may associate with virus pathogenesis, virus sensitivity to neutralizing antibodies (nAbs) and disease progression. To investigate the role of each variable loop in Env function, we generated a panel of JRFL gp160 loop deletion mutants and examined the effects of each loop deletion on Env expression, Env cell surface display and Env-mediated virus entry into permissive cells. We found that deletion of V1 and V2 (DeltaV1V2), or loop D (DeltalpD) abolished virus entry, the same effect as deletion of V3 (DeltaV3), while deletion of V3 crown (DeltaV3C) significantly enhanced virus assembly and entry. We further found that deletion of V4 (DeltaV4) or V5 (DeltaV5), or replacement of V4 or V5 with flexible linkers of the same lengths knocked out the receptor and coreceptor binding sites in gp120, but significantly enhanced the exposure of the N-trimer structure and the membrane proximal external region (MPER) in gp41. Although deletion of V4 or V5 did not affect Env expression, they negatively affected Env cell surface display, leading to the failure in virus assembly and subsequent entry. Taken together, we found that Env variable loops were indispensable for Env structural integrity and virus entry. Our findings may have implications for development of HIV-1 vaccine immunogens and therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/185534
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYuan, T-
dc.contributor.authorLi, J-
dc.contributor.authorZhang, M-
dc.date.accessioned2013-08-13T08:16:50Z-
dc.date.available2013-08-13T08:16:50Z-
dc.date.issued2013-
dc.identifier.citationPLoS One, 2013, v. 8 n. 8, p. Article numbere 69789-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/185534-
dc.description.abstractHIV-1 envelope (Env) glycoprotein is a trimer of heterodimer of gp120 and gp41, and derives from a trimeric glycoprotein precursor, gp160. Gp120 contains five conserved regions that are interspersed with 5 variable loop regions (V1-V5). Env variations in variable loop length and amino acid composition may associate with virus pathogenesis, virus sensitivity to neutralizing antibodies (nAbs) and disease progression. To investigate the role of each variable loop in Env function, we generated a panel of JRFL gp160 loop deletion mutants and examined the effects of each loop deletion on Env expression, Env cell surface display and Env-mediated virus entry into permissive cells. We found that deletion of V1 and V2 (DeltaV1V2), or loop D (DeltalpD) abolished virus entry, the same effect as deletion of V3 (DeltaV3), while deletion of V3 crown (DeltaV3C) significantly enhanced virus assembly and entry. We further found that deletion of V4 (DeltaV4) or V5 (DeltaV5), or replacement of V4 or V5 with flexible linkers of the same lengths knocked out the receptor and coreceptor binding sites in gp120, but significantly enhanced the exposure of the N-trimer structure and the membrane proximal external region (MPER) in gp41. Although deletion of V4 or V5 did not affect Env expression, they negatively affected Env cell surface display, leading to the failure in virus assembly and subsequent entry. Taken together, we found that Env variable loops were indispensable for Env structural integrity and virus entry. Our findings may have implications for development of HIV-1 vaccine immunogens and therapeutics.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleHIV-1 envelope glycoprotein variable loops are indispensable for envelope structural integrity and virus entryen_US
dc.typeArticleen_US
dc.identifier.emailLi, J: joyli@hku.hk-
dc.identifier.emailZhang, M: zhangmy@hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0069789-
dc.identifier.pmid23936354-
dc.identifier.scopuseid_2-s2.0-84881006882-
dc.identifier.hkuros219330-
dc.identifier.volume8-
dc.identifier.issue8-
dc.identifier.spageArticle numbere 69789-
dc.identifier.epageArticle numbere 69789-
dc.identifier.isiWOS:000324518400023-
dc.publisher.placeUnited States-

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