Blood Monocytes Harbor HIV Type 1 Strains with Diversified Phenotypes Including Macrophage‐Specific CCR5 Virus

Abstract

These data suggest that HIV-1 circulating in blood monocytes represents diverse HIV-1 with multiple phenotypes and that MDMS-R5 viruses may play an important role in infection with and persistence of HIV-1 within the monocyte/macrophage lineage.

Virus Entry via the Alternative Coreceptors CCR3 and FPRL1 Differs by Human Immunodeficiency Virus Type 1 Subtype

“…We also noted some subtype-specific differences in the frequency with which alternative CoRs could be used for entry (Table 1). Significant differences were a more frequent use of APJ in subtype B, a less frequent use of CMKLR1 in subtype C, a less frequent use of FPRL1 in subtype B, and a more frequent use of CXCR4 in subtype D. Several prior reports have noted the high frequency of R5R3 viruses that show efficient entry via both CCR5 and CCR3 (1-3, 5, 17, 61), and some (77,78) suggest possible target cell adaptation by this prevalent subset of HIV-1 phenotypes. Differences in cell lines used for typing CCR3 use could have contributed to distinct outcomes between our results and prior reports; specifically, U87/CD4/CCR3 cells obtained from the AIDS Research and Reference Reagent Program and used in the study by Morris et al (54) express 100-fold lower levels of CCR3 than the NP-2/CD4/CCR3 cells we have employed (data not shown).…”

“…The importance of alternative CoRs other than CXCR4 has remained elusive despite many studies (1,30,70,81). Expansion of CoR use from CCR5 to include CXCR4 is frequently associated with the ability to use additional alternative CoRs for viral entry (8,16,20,63,79) in most but not all studies (29,33,40,77,78). This finding suggests that the sequence changes in HIV-1 env required for use of CXCR4 as an additional or alternative CoR (14,15,31,37,41,57) are likely to increase the potential to use other alternative CoRs.…”

Immuno-Pharmacological Targeting of Virus-Containing Compartments in HIV-1-Infected Macrophages

“…The levels of the soluble form of the receptor (suPAR) in plasma or liquor have been monitored in several pathological conditions, including HIV infection. evidence either in favor or against the infection of monocytes in vivo [21][22][23]. Strikingly, in the case of a laboratory worker infected with a laboratory-adapted X4 HIV-1 strain, viral isolates showed evidence of mutations and adaptation to replicate in macrophages [24].…”

HIV-1 Pathogenesis: The Virus

“…Monocytes and dendritic cells isolated from blood express very low levels of CD4 (Lee et al 1999). Peripheral monocytes have been reported to be infected in vivo (Zhu et al 2002;Fulcher et al 2004;Ellery et al 2007;Xu et al 2008), along with complex collections of other blood myeloid cells (Centlivre et al 2011). However, a recent analysis of viral DNA in blood cell subsets failed to detect a significant amount of viral DNA in the monocyte pool (Joseffson et al 2011).…”