Figure 1.

The role of neutrophils in HIV infection. Neutrophils contain cytoplasmic granules, consisting of various antimicrobial mediators, notably defensins, that inhibit HIV replication. In addition, neutrophils produce superoxide, which is converted to reactive oxygen species (ROS) that can kill phagocytosed microbes and mediate neutrophil extracellular trap (NET) formation. On the downside, ROS also lead to tissue damage and activation-induced cell death. ROS production is enhanced during HIV infection, mediated by various viral proteins, most notably the envelope glycoprotein, gp120 and the regulatory protein, trans-activator of transcription protein (Tat), as well as by the regulatory proteins, negative regulating factor (Nef), virus protein r (Vpr), and reverse transcriptase. HIV inhibits both the number and function of neutrophils in the blood through multiple mechanisms (more detail is provided in the text). HIV-infected individuals also express high levels of programmed death-ligand 1 (PD-L1) that binds to programmed death-1 (PD-1) on T-cells, thereby contributing to T-cell dysfunction and exhaustion. NET, neutrophil extracellular trap; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; ROS, reactive oxygen species.