Pannexin1 hemichannels are critical for HIV infection of human primary CD4⁺ T lymphocytes

HIV is a major public health issue, and infection of CD4⁺ T lymphocytes is one of its key features. Whereas several cellular proteins have been identified that facilitate viral infection and replication, the role of hemichannels in these processes has not been fully characterized. We now show that the HIV isolates, R5 and X4, induced a transient-early (5-30 min) and a later, persistent (48-120 h) opening of Panx1 hemichannels, which was dependent on the binding of HIV to CD4 and CCR5/CXCR4 receptors. Blocking Panx1 hemichannels by reducing their opening or protein expression inhibited HIV replication in CD4⁺ T lymphocytes. Thus, our findings demonstrate that Panx1 hemichannels play an essential role in HIV infection.