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1.
J Virol ; 93(10)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30842323

RESUMO

HIV-1 has been shown to evolve independently in different anatomical compartments, but studies in the female genital tract have been inconclusive. Here, we examined evidence of compartmentalization using HIV-1 subtype C envelope (Env) glycoprotein genes (gp160) obtained from matched cervicovaginal lavage (CVL) and plasma samples over 2 to 3 years of infection. HIV-1 gp160 amplification from CVL was achieved for only 4 of 18 acutely infected women, and this was associated with the presence of proinflammatory cytokines and/or measurable viremia in the CVL. Maximum likelihood trees and divergence analyses showed that all four individuals had monophyletic compartment-specific clusters of CVL- and/or plasma-derived gp160 sequences at all or some time points. However, two participants (CAP177 and CAP217) had CVL gp160 diversity patterns that differed from those in plasma and showed restricted viral flow from the CVL. Statistical tests of compartmentalization revealed evidence of persistent compartment-specific gp160 evolution in CAP177, while in CAP217 this was intermittent. Lastly, we identified several Env sites that distinguished viruses in these two compartments; for CAP177, amino acid differences arose largely through positive selection, while insertions/deletions were more common in CAP217. In both cases these differences contributed to substantial charge changes spread across the Env. Our data indicate that, in some women, HIV-1 populations within the genital tract can have Env genetic features that differ from those of viruses in plasma, which could impact the sensitivity of viruses in the genital tract to vaginal microbicides and vaccine-elicited antibodies.IMPORTANCE Most HIV-1 infections in sub-Saharan Africa are acquired heterosexually through the genital mucosa. Understanding the properties of viruses replicating in the female genital tract, and whether these properties differ from those of more commonly studied viruses replicating in the blood, is therefore important. Using longitudinal CVL and plasma-derived sequences from four HIV-1 subtype C-infected women, we found fewer viral migrations from the genital tract to plasma than in the opposite direction, suggesting a mucosal sieve effect from the genital tract to the blood compartment. Evidence for both persistent and intermittent compartmentalization between the genital tract and plasma viruses during chronic infection was detected in two of four individuals, perhaps explaining previously conflicting findings. In cases where compartmentalization occurred, comparison of CVL- and plasma-derived HIV sequences indicated that distinct features of viral populations in the CVL may affect the efficacy of microbicides and vaccines designed to provide mucosal immunity.


Assuntos
Genitália Feminina/virologia , Proteína gp160 do Envelope de HIV/genética , Vagina/virologia , Adolescente , Adulto , Feminino , Anticorpos Anti-HIV/genética , Proteína gp160 do Envelope de HIV/metabolismo , Infecções por HIV/virologia , Soropositividade para HIV/genética , HIV-1/imunologia , HIV-1/metabolismo , HIV-1/patogenicidade , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Especificidade de Órgãos/genética , Filogenia , RNA Viral/genética , Infecções do Sistema Genital/virologia , África do Sul , Carga Viral , Viremia/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
2.
PLoS Comput Biol ; 10(1): e1003458, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24499938

RESUMO

Sharing results, techniques, and challenges is paramount to advance our understanding of any field of science. In the scientific community this exchange of ideas is mainly made possible through national and international conferences. Scientists have the opportunity to showcase their work, receive feedback, and improve their presentation skills. However, conferences can be large and intimidating for young researchers. In addition, for many of the more prestigious conferences, the very high number of submissions and low selection rate are major limitations to aspiring young researchers aiming to present their work to the scientific community. To improve student participation and proliferation of information, regional student groups have successfully organized conferences and symposia specifically aimed at students. This gives more students the opportunity to present their work and receive valuable experience and insight from peers and leaders in the field. At the same time, it is an ideal way for students to gain familiarity with the conference experience. In this paper, we highlight some of the benefits of participating in such student conferences, and we review the challenges we have encountered when organizing them. Both topics are illustrated in detail with examples from different ISCB Student Council Regional Student Groups.


Assuntos
Biologia Computacional/educação , Biologia Computacional/métodos , Estudantes , Comunicação , Congressos como Assunto , Humanos , Sociedades Científicas
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