HIV-1 Remodels Nuclear Pores via Cell-Cell Signaling to Infect Resting T Cells
A recent study published in Nature reveals how HIV-1 overcomes the natural resistance of resting CD4+ T cells to infection. While resting T cells are typically refractory to cell-free virus infection due to barriers at the nuclear pore complex (NPC), the virus exploits cell-cell spread mechanisms to bypass this bottleneck. The research demonstrates that contact between infected and uninfected T cells triggers CD4-LCK signaling, which activates CDK1 independently of cell-cycle entry. This activation leads to the phosphorylation of nucleoporins, effectively remodeling the NPC to facilitate the nuclear import of the HIV-1 capsid. This process licenses infection in resting T cells, explaining why cell-cell spread dominates HIV-1 transmission in vivo compared to cell-free virions, which do not trigger this specific signaling response. The findings provide a new paradigm for understanding HIV-1 pathogenesis and suggest that the virus has evolved to selectively activate cellular signaling during direct cell contact to regulate infection at the nuclear envelope stage.
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HIV-1 Remodels Nuclear Pores via Cell-Cell Signaling to Infect Resting T Cells
A recent study published in Nature reveals how HIV-1 overcomes the natural resistance of resting CD4+ T cells to infection. While resting T cells are typically refractory to cell-free virus infection due to barriers at the nuclear pore complex (NPC), the virus exploits cell-cell spread mechanisms to bypass this bottleneck. The research demonstrates that contact between infected and uninfected T cells triggers CD4-LCK signaling, which activates CDK1 independently of cell-cycle entry. This activation leads to the phosphorylation of nucleoporins, effectively remodeling the NPC to facilitate the nuclear import of the HIV-1 capsid. This process licenses infection in resting T cells, explaining why cell-cell spread dominates HIV-1 transmission in vivo compared to cell-free virions, which do not trigger this specific signaling response. The findings provide a new paradigm for understanding HIV-1 pathogenesis and suggest that the virus has evolved to selectively activate cellular signaling during direct cell contact to regulate infection at the nuclear envelope stage.
Nature