RESUMEN
We analyzed the role of human immunodeficiency virus (HIV)-1 matrix protein (MA) during the virus replication afferent phase. Single-round infection of H9 T lymphocytes showed that the combined mutation of MA Lys residues 26-27 in MA reported nuclear localization signal (NLS)-1 impaired infectivity, abrogated 2-LTR-circle formation and significantly reduced integration. However, the mutation did not affect viral DNA docking to chromatin in either interphasic or mitotic cells, indicating that MA N-terminal basic domain should not represent a major determinant of HIV-1 nuclear import in T lymphocytes. These data point to a previously unreported role of MA in the late, post-chromatin-binding, afferent phase of HIV-1 replication cycle.
Asunto(s)
Productos del Gen gag/fisiología , Antígenos VIH/fisiología , VIH-1/fisiología , Proteínas Virales/fisiología , Ciclo Celular , Línea Celular , Cromatina/metabolismo , ADN Viral/metabolismo , Productos del Gen gag/genética , Antígenos VIH/genética , VIH-1/metabolismo , Humanos , Mutación , Linfocitos T/virología , Proteínas Virales/genética , Integración Viral , Replicación Viral , Productos del Gen gag del Virus de la Inmunodeficiencia HumanaRESUMEN
We examined the influence of mitosis on the kinetics of human immunodeficiency virus type 1 integration in T cells. Single-round infection of cells arrested in G1b or allowed to synchronously proceed through division showed that mitosis delays virus integration until 18-24 h postinfection, whereas integration reaches maximum levels by 15 h in G1b-arrested cells. Subcellular fractionation of metaphase-arrested cells indicated that, while nuclear envelope disassembly facilitates docking of viral DNA to chromatin, chromosome condensation directly antagonizes and therefore delays integration. As a result of the balance between the two effects, virus integration efficiency is eventually up to threefold greater in dividing cells. At the single-cell level, using a green fluorescent protein-expressing reporter virus, we found that passage through mitosis leads to prominent asymmetric segregation of the viral genome in daughter cells without interfering with provirus expression.
Asunto(s)
Ciclo Celular , Regulación Viral de la Expresión Génica , VIH-1/patogenicidad , Linfocitos T/virología , Integración Viral , Animales , Cromatina/metabolismo , ADN Viral/genética , ADN Viral/metabolismo , Infecciones por VIH/virología , VIH-1/genética , Humanos , Mitosis , Membrana Nuclear/metabolismoRESUMEN
We report that human T cells persistently infected with primate foamy virus type 1 (PFV-1) display an increased capacity to bind human immunodeficiency virus type 1 (HIV-1), resulting in increased cell permissiveness to HIV-1 infection and enhanced cell-to-cell virus transmission. This phenomenon is independent of HIV-1 receptor, CD4, and it is not related to PFV-1 Bet protein expression. Increased virus attachment is specifically inhibited by heparin, indicating that it should be mediated by interactions with heparan sulfate glycosaminoglycans expressed on the target cells. Given that both viruses infect similar animal species, the issue of whether coinfection with primate foamy viruses interferes with the natural course of lentivirus infections in nonhuman primates should be considered.