Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
PLoS One ; 12(11): e0185959, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29149197

RESUMO

Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Antígenos CD4/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , HIV-1/genética , Vacinas contra a AIDS/imunologia , Adolescente , Adulto , Sítios de Ligação , Feminino , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
PLoS One ; 12(10): e0182443, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29045410

RESUMO

Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART). This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Caracteres Sexuais , Estudos de Coortes , Progressão da Doença , Evolução Molecular , Feminino , Glicosilação , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/genética , Humanos , Funções Verossimilhança , Masculino , Nucleotídeos/genética , Filogenia , Fatores de Tempo , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...