FIGURE 2.

HIV-1 has evolved mechanism to evade host immune responses in macrophages. (A) HIV-1 infected macrophages are refractory to the cytopathic effects of viral infection. Infected cells usually undergo apoptosis or cell-mediated killing upon viral infection. HIV-1 upregulates certain factors to evade apoptosis. HIV-1 envelope glycoprotein binds to M-CSF to downregulate TRAIL-receptor and upregulate anti-apoptotic genes. HIV-infected macrophages express higher levels of TREM1, which upregulates and translocates Bim to the mitochondria to downregulate BCL-2 induced apoptosis. Additionally, HIV-infected macrophages have increased telomerase activity, triggering less DNA damage and sustained infection. (B) HIV-1 induces mechanisms to evade IFN responses in infected macrophages through accessory proteins. TREX1 binds to excess HIV DNA during reverse transcription to suppress IFN responses. HIV-1 capsid binds to and removes CPSF6 and cyclophilins to silence downstream innate sensors of IFN pathways. HIV-1 Vif and Vpr bind to TBK1, preventing phosphorylation and downstream IFN induction. HIV-1 Vpr also binds to SLX4 complex with reverse transcribed HIV-1 DNA, like TREX1 to degrade nucleic acids and increase cellular replication stress, leading to G2/M cell cycle arrest and prevent IFN response. (C) CTLs recognize peptide antigens presented by MHC-I and release cytotoxic particles to kill infected cells. HIV-1 infected macrophages are resistant to CTL killing as CTLs require both granzyme B and caspase-3 to efficiently kill HIV-1 infected macrophages unlike CD4+ T cells which only need granzyme B. CTL binding to MHC-I only triggers release of granzyme B, which renders a much slower and less efficient killing of macrophages.