RESUMO
Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and subjects with chronic infections in the context of subtype C heterosexual transmission. We found that the transmitted viruses all used CCR5 and required high levels of CD4 to infect target cells, suggesting selection for replication in T cells and not macrophages after transmission. In addition, the transmitted viruses were more likely to use a maraviroc-sensitive conformation of CCR5, perhaps identifying a feature of the target T cell. We confirmed an earlier observation that the transmitted viruses were, on average, modestly underglycosylated relative to the viruses from chronically infected subjects. This difference was most pronounced in comparing the viruses in acutely infected men to those in chronically infected women. These features of the transmitted virus point to selective pressures during the transmission event. We did not observe a consistent difference either in heterologous neutralization sensitivity or in sensitivity to soluble CD4 between the two groups, suggesting similar conformations between viruses from acute and chronic infection. However, the presence or absence of glycosylation sites had differential effects on neutralization sensitivity for different antibodies. We suggest that the occasional absence of glycosylation sites encoded in the conserved regions of env, further reduced in transmitted viruses, could expose specific surface structures on the protein as antibody targets.
Assuntos
Variação Genética , Infecções por HIV/metabolismo , HIV-1/metabolismo , Receptores CCR5/metabolismo , Linfócitos T/virologia , Proteínas do Envelope Viral/metabolismo , Sequência de Bases , Clonagem Molecular , Análise por Conglomerados , Estudos de Coortes , Feminino , Glicosilação , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Malaui , Masculino , Dados de Sequência Molecular , Testes de Neutralização , Filogenia , Conformação Proteica , Receptores CCR5/química , Alinhamento de Sequência , Análise de Sequência de DNA , Fatores Sexuais , África do Sul , Linfócitos T/imunologia , Proteínas do Envelope Viral/genética , Replicação Viral/fisiologiaRESUMO
To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.
Assuntos
Doenças dos Símios Antropoides/epidemiologia , Cercopithecidae , Infecções por Enterovirus/veterinária , Gorilla gorilla , Doenças dos Macacos/epidemiologia , Pan troglodytes , África/epidemiologia , Animais , Doenças dos Símios Antropoides/virologia , Linhagem Celular Tumoral , Enterovirus/classificação , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Humanos , Doenças dos Macacos/virologia , Estudos Soroepidemiológicos , SorotipagemRESUMO
Human parvovirus 4 infections are primarily associated with parenteral exposure in western countries. By ELISA, we demonstrate frequent seropositivity for antibody to parvovirus 4 viral protein 2 among adult populations throughout sub-Saharan Africa (Burkina Faso, 37%; Cameroon, 25%; Democratic Republic of the Congo, 35%; South Africa, 20%), which implies existence of alternative transmission routes.