Table 1.
Reports of HIV-1/SIV infection and reservoir characteristics in myeloid cells in blood and tissue
Myeloid cell in blood/tissue | Evidence of HIV-1/SIV infection and reservoir |
---|---|
| |
Blood • Monocytes • Monocyte-derived macrophages |
▪ Bone marrow progenitor cells are potential sites of initial HIV-1 infection [27]. ▪ Detection of HIV-1 DNA in highly purified monocytes from vsPWH [26, 29–31]. ▪ The mean half-life of HIV-1 in CD14+ monocytes (41.3 months) was significantly lower compared with activated CD4+ T cells (19.8 months) in vsPWH [28]. ▪ Intact proviral DNA was measured in monocytes and infectious replication-competent virus was produced from monocyte-derived macrophages from vsPWH [32••]. |
Central nervous system • Microglia • Brain macrophages |
▪ HIV-1 reservoirs in the brain, in microglia and brain macrophages, persist despite ART in PWH [33, 34]. ▪ Total intact HIV-1 DNA in the frontal lobe was similar between ART-suppressed and viremic PWH [35••]. ▪ HIV-1 V3 env sequences were measured from the nuclei of CD68+ macrophages isolated from the frontal lobe of vsPWH [35••]. ▪ Brain myeloid cells (BrMCs), isolated from NHP and rapid autopsy of vsPWH, contained infectious replication-competent virus and sequencing revealed homogeneity in BrMCs sequences which were also distinct from peripheral sequences [36••]. ▪ In both dual inoculated (SIV/DeltaB670 and SIV/17E-Fr) ART-suppressed pig-tailed macaques and SIVmac251-infected ART-suppressed macaques [37, 38, 39••]: ⚬ SIV DNA was detectable in CD11b+ brain macrophages. ⚬ Latently infected CD11b+ brain macrophages were reactivatable ex vivo to produce infectious virus. |
Lung • Alveolar macrophages • Interstitial macrophages |
▪ HIV-1 infection of alveolar macrophages requires cell-to-cell transmission from infected CD4+ T cells [41••]. ▪ In both dual inoculated (SIV/DeltaB670 and SIV/17E-Fr) ART-suppressed pig-tailed macaques and SIVmac251-infected ART-suppressed macaques [38, 39••, 40]: ⚬ SIV DNA was detectable in CD11b+ lung macrophages. ⚬ Latently infected CD11b+ lung macrophages were reactivatable ex vivo to produce infectious virus. |
Gastrointestinal tract • Intestinal macrophages |
▪ HIV-1 proviral DNA and p24 were measured in intestinal macrophages from the duodenum of vsPWH on long-term ART [42]. ▪ Higher total HIV-1 DNA levels compared with CD4+ T cell HIV-1 DNA levels indicate that myeloid cells may compose part of the viral reservoir in the rectum [43]. |
Spleen • Splenic macrophages |
▪ HIV-1 env-nef single genome sequencing of spleen tissue from vsPWH revealed two distinct phylogenetic patterns which indicate that there may be infection two major cell types, myeloid cells and CD4+ T cells [56]. ▪ In both dual inoculated (SIV/DeltaB670 and SIV/17E-Fr) ART-suppressed pigtailed macaques and SIVmac251-infected ART-suppressed macaques [38, 39••, 40]: ⚬ SIV DNA was detectable in CD11b+ splenic macrophages. ⚬ Latently infected CD11b+ splenic macrophages were reactivatable ex vivo to produce infectious virus. |
Liver • Kupffer cells • Liver macrophages |
▪ Liver macrophages isolated from vsPWH contain HIV-1 DNA; however, they cannot be reactivated to produce replication competent virus [47••]. |
Genital tract • Male urethral macrophages • Female reproductive tract macrophages |
▪ Penile urethral macrophages are initial targets of HIV-1 [44]. ▪ HIV-1 DNA is detectable in urethral macrophages from vsPWH through nested PCR for HIV-1 gp120 V loops and Alu-gag nested PCR [45••]. ▪ Urethral macrophages from vsPWH contain HIV-1 reservoirs that are inducible and produce infectious virus [46]. ▪ Using vaginal tissue explants and GFP-reporter R5 HIV-1 viral strains, viral uptake was demonstrated in HAM56+ vaginal macrophages post-inoculation of whole explant tissue and CD13+ selected vaginal macrophages produced p24 following infection in culture [57]. ▪ CD14+ selected endometrial and decidual macrophages produced p24 in culture following infection with HIV-1BAL [58]. |