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Evolutionary and structural features of the C2, V3 and C3 envelope regions underlying the differences in HIV-1 and HIV-2 biology and infection

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dc.contributor.authorBarroso, Helena
dc.contributor.authorBorrego, Pedro
dc.contributor.authorBártolo, Inês
dc.contributor.authorMarcelino, José Maria
dc.contributor.authorFamilia, Carlos
dc.contributor.authorQuintas, Alexandre
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2023-08-31T11:39:41Z
dc.date.available2023-08-31T11:39:41Z
dc.date.issued2011
dc.date.updated2023-02-03T14:37:40Z
dc.description.abstractBackground Unlike in HIV-1 infection, the majority of HIV-2 patients produce broadly reactive neutralizing antibodies, control viral replication and survive as elite controllers. The identification of the molecular, structural and evolutionary footprints underlying these very distinct immunological and clinical outcomes may lead to the development of new strategies for the prevention and treatment of HIV infection. Methodology/Principal Findings We performed a side-by-side molecular, evolutionary and structural comparison of the C2, V3 and C3 envelope regions from HIV-1 and HIV-2. These regions contain major antigenic targets and are important for receptor binding. In HIV-2, these regions also have immune modulatory properties. We found that these regions are significantly more variable in HIV-1 than in HIV-2. Within each virus, C3 is the most entropic region followed by either C2 (HIV-2) or V3 (HIV-1). The C3 region is well exposed in the HIV-2 envelope and is under strong diversifying selection suggesting that, like in HIV-1, it may harbour neutralizing epitopes. Notably, however, extreme diversification of C2 and C3 seems to be deleterious for HIV-2 and prevent its transmission. Computer modelling simulations showed that in HIV-2 the V3 loop is much less exposed than C2 and C3 and has a retractile conformation due to a physical interaction with both C2 and C3. The concealed and conserved nature of V3 in the HIV-2 is consistent with its lack of immunodominancy in vivo and with its role in preventing immune activation. In contrast, HIV-1 had an extended and accessible V3 loop that is consistent with its immunodominant and neutralizing nature. Conclusions/Significance We identify significant structural and functional constrains to the diversification and evolution of C2, V3 and C3 in the HIV-2 envelope but not in HIV-1. These studies highlight fundamental differences in the biology and infection of HIV-1 and HIV-2 and in their mode of interaction with the human immune system and may inform new vaccine and therapeutic interventions against these viruses.pt_PT
dc.description.sponsorshipThis work was supported by projects PTDCSAU-FCF6767/2006 from Fundo para a Ciencia e Tecnologia, Portugal and by Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN), from the European Union. PB and IB are supported by PhD grants from Fundo para a Ciencia e Tecnologia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBarroso H, Borrego P, Bártolo I, Marcelino JM, Família C, Quintas A, et al. Evolutionary and structural features of the c2, v3 and c3 envelope regions underlying the differences in hiv-1 and hiv-2 biology and infection. PLOS ONE [Internet]. 20 de janeiro de 2011;6(1):e14548. Disponível em: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014548pt_PT
dc.identifier.doi10.1371/journal.pone.0014548pt_PT
dc.identifier.eid2-s2.0-79251624890
dc.identifier.slugcv-prod-1108463
dc.identifier.urihttp://hdl.handle.net/10451/59100
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPlospt_PT
dc.relationPTDCSAU-FCF6767/2006pt_PT
dc.relationCollaborative HIV and Anti-HIV Drug Resistance Network
dc.relation.publisherversionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014548pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleEvolutionary and structural features of the C2, V3 and C3 envelope regions underlying the differences in HIV-1 and HIV-2 biology and infectionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCollaborative HIV and Anti-HIV Drug Resistance Network
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/223131/EU
oaire.citation.issue1pt_PT
oaire.citation.startPagee14548pt_PT
oaire.citation.titlePLoS ONEpt_PT
oaire.citation.volume6pt_PT
oaire.fundingStreamFP7
person.familyNameBarroso
person.familyNameBorrego
person.familyNameBártolo
person.familyNameMARCELINO
person.familyNameFamilia
person.familyNameQuintas
person.familyNameTaveira
person.givenNameHelena
person.givenNamePedro
person.givenNameInês
person.givenNameJOSÉ MARIA
person.givenNameCarlos
person.givenNameAlexandre
person.givenNameNuno
person.identifierB-3374-2008
person.identifierhttps://scholar.google.pt/citations?hl=pt-PT&user=kcGK4EYAAAAJ
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project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.cv.cienciaid661E-F5CB-F85A | Inês Bártolo
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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