RESUMO
This data article describes the infectivity of transmitted/founder (TF) and non-TF (NT) HIV-1 viruses derived from primary CD4+ T cells treated with or without IFN-α, over a period of 12 days. TF and NT viruses described in this article were derived from the same individual (one of each from 8 infants who acquired HIV infection through mother-to-child transmission (MTCT). IFN-α resistance to both TF and NT viruses was studied by infecting TZM-bl cells and measuring luciferase expression (expressed as relative light units, RLU). Measurement of luciferase expression is extremely sensitive and allows quantification of even small changes in gene expression at the transcriptional level.
RESUMO
Type I interferons, particularly interferon-alpha (IFN-α), play a vital role in the host's anti-viral defenses by interfering with viral replication. However, the virus rapidly evolves to exploit the IFN-α response for its replication, spread, and pathogenic function. In this study, we attempted to determine IFN-α susceptibility and productivity of infectious transmitted/founder (TF) (n = 8) and non-transmitted (NT) viruses (n = 8) derived from HIV-1 infected infants. Independent experiments were carried out to determine IFN-α resistance, replication fitness, and viral productivity in CD4+ T cells over a short period. In vitro studies showed that TF viruses were resistant to IFN-α during the very near moment of transmission, but in the subsequent time points, they became susceptible to IFN-α. We did not observe much difference in replicative fitness of the TF viruses in cultures treated with and without IFN-α, but the difference was significant in the case of NT viruses obtained from the same individual. Despite increased susceptibility to IFN-α, NT viruses produced more viral particles than TF viruses. Similar results were also obtained in cultures treated with maraviroc (MVC). The study identified unique characteristics of TF viruses thus prompting further investigation into virus-host interaction occurring during the early stages of HIV infection.
Assuntos
HIV-1/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interferon-alfa/farmacologia , Receptores CCR5/genética , Vírion/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Antagonistas dos Receptores CCR5/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/virologia , Expressão Gênica , Células HEK293 , Inibidores da Fusão de HIV/farmacologia , HIV-1/genética , HIV-1/metabolismo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lactente , Maraviroc/farmacologia , Mariposas , Cultura Primária de Células , Receptores CCR5/imunologia , Carga Viral/efeitos dos fármacos , Vírion/genética , Vírion/metabolismo , Internalização do Vírus/efeitos dos fármacosRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.