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. 2022 Dec 27;135(22):2667–2676. doi: 10.1097/CM9.0000000000002479

Figure 1.

Figure 1

Innate immune response and HIV reservoir. (A) HIV reservoirs. HIV reservoirs are established early in HIV infection and hide in immune-privileged anatomic sites, including the brain, bone marrow, lungs, lymph nodes, and GALT. (B) Macrophages and HIV reservoirs. Host restriction factors, including SAMHD1, APOBEC3, and MX2, can influence HIV latency in macrophages by inhibiting RT. (C) DC–NK cell crosstalk. DCs are activated by HIV; secrete pro-inflammatory cytokines, including IL-12, IL-15, and IFNs; and stimulate NK cells. Activated NK cells secrete IFN-γ to promote DC maturation and Th1 immunity. DC–NK cell crosstalk is attenuated in HIV infection. (D) DCs and HIV reservoirs. Viral restriction factors play an important role in HIV reservoirs in DCs, including SAMHD1, IFITM proteins, TRIM5α, Tetherin, and APOBEC3. HIV can counteract the immune response induced by these host restriction factors by encoding viral accessory proteins, including Vpr and Vif, which can antagonize APOBEC3, and Vpu and nef, which can antagonize Tetherin. (E) NK cells and HIV reservoirs. NK cells can recognize and eliminate HIV-infected cells through many different mechanisms, mainly cytokine secretion, ADCC, cytotoxic granule exocytosis, and death receptor pathway activity, which may be effective for reducing the size of the latent HIV reservoir and become a promising strategy for achieving a functional HIV cure. ADCC: Antibody-dependent cellular cytotoxicity; APOBEC3: Apolipoprotein B Editing Complex3; CCR5: C-C chemokine receptor 5; CD4:cluster of differentiation 4; DCs: Dendritic cells; GALT: Gut-associated lymphoid tissue; HIV: Human immunodeficiency virus; HLA-B: Hhuman leukocyte antigen-B; IFITM: Interferon-induced transmembrane; IFN-γ: Interferon γ; IL-12: Interleukin-12; KIR: Killer immunoglobulin-like receptors; MX2: Myxovirus-resistance protein 2; NK: Natural killer; NKG2DL: Natural killer group 2 member D ligand; NKG2D: Natural killer group 2D; RT: Reverse transcription; SAMHD1: Sterile α-motif/histidine-aspartate domain-containing protein 1; Tetherin: Bone marrow stromal antigen 2; Th1 immunity: T helper 1 immunity; TNF: Tumor necrosis factor; TRIM5α: Tripartite motif containing 5 alpha.