Figure 1

Schematic model of HIV-1 replication and restrictions thereof in activated and resting CD4⁺ T lymphocytes. (A) Activated CD4⁺ T lymphocytes are fully permissive to HIV-1 replication and all steps of the viral life cycle from entry (facilitated by loosening of the actin cortex), RT, nuclear import, integration, viral gene expression to synthesis of new viral proteins, particle assembly and release are efficient. Cellular dNTP levels are high despite the presence of high SAMHD1 expression, suggesting that the activity of the enzyme may be downregulated in these cells (indicated by the question mark). (B) HIV-1 infection of resting CD4⁺ T lymphocytes is abortive. HIV-1 overcomes the rigid actin cortex barrier by inducing Env-chemokine receptor signaling. RT is initiated but stalls before viral DNA synthesis is completed. Presumably due to the high activity of SAMHD1, dNTP levels in the cytoplasm are low and limit RT reactions. (C) Delivery of Vpx surmounts the SAMHD1 barrier and allows HIV-1 to infect resting CD4⁺ T lymphocytes. SAMHD1 is targeted by Vpx for proteasomal degradation, which is paralleled by an elevation of cellular dNTP levels. HIV-1 infection proceeds through RT, nuclear import and integration. Some viral gene expression is observed but no infectious progeny is released, suggesting the existence of yet uncharacterized additional blocks in the late phase of the viral life cycle.