Virion Associated Importin Subunit Beta-1 Augments Nuclear Import of HIV-1 Pre-Integration Complex

Import of proviral genome from the cytoplasm to the nucleus is a decisive step in the HIV-1 infection cycle, regulating which can decide the fate of HIV-1 infectivity. Exploring the heterogeneity in the replication potential of viruses emerging from various producer cells, we compared the infectivity dynamics of viruses produced by CD4+ T lymphocytes, a cell type that supports the HIV-1 propagation, with those from astrocytes that allow for limited viral replication. We found the viruses emerging from these two cell types not only differed in their infectivity, but also in the host proteins that get associated with these virions. We focused on Importin β1, an autonomous nuclear transport receptor, which was present in the virion fractions from CD4+ T lymphocytes but absent in those from astrocytes. Our analysis revealed that Importin β1 gets associated with the virus through interactions with HIV-1 Gag and Capsid proteins. Using Importin β1 knockout cell models, we found that virion-associated Importin β1 enhanced viral infectivity by facilitating the import of the viral Pre-integration complex (PIC) into the nucleus of an infected cell. Linking positive factors, such as Importin β1, to emerging virions can determine the viral infectivity in subsequent infection rounds, influencing disease progression.