Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types.

Abstract

To characterize the host range of different strains of HIV-1, we have used four types of cells, primary monocyte-derived macrophages (MDM), primary PBL, a promonocyte cell line (U937), and a CD4+ T cell line (SUP-T1). These cells were infected with three prototype strains of HIV-1, a putative lymphocyte-tropic strain (IIIB), and two putative monocyte-tropic strains (SF162 and DV). Infections were monitored by assays for infectious virus, for cell-free and cell-associated viral antigen (p24), and for the proportion of cells infected by immunohistochemical staining. It was concluded that: (a) the use of four different cell types provides a useful biological matrix for distinguishing the tropism of different strains of HIV-1; this matrix yields more information than the infection of any single cell type. (b) A monocyte-tropic strain of HIV-1, such as strain SF162, shows a reciprocal host range when compared with a lymphocyte-tropic strain such as IIIB; strain SF162 replicates well in primary MDM but not in U937 or SUP-T1 cells, while strain IIIB replicates well in both U937 and SUP-T1 cells but not in MDM. (c) Both lymphocyte-tropic and monocyte-tropic strains of HIV-1 replicate well in PBL. (d) The promonocyte cell line, U937, and the T cell line, SUP-T1, differ markedly from primary cells, such as MDM and PBL, in their ability to support the replication of different strains of HIV-1; these cell lines cannot be used as surrogates for primary cells in host range studies of HIV-1 strains.

Cross-Neutralization Activity of Single-Chain Variable Fragment (scFv) Derived from Anti-V3 Monoclonal Antibodies Mediated by Post-Attachment Binding

“…We also reported that passive transfer of anti-V3 MAb KD-247 successfully suppressed HIV-1 viral load in vivo (16). Given the recent studies showing that anti-V3 antibodies exert immune pressure on circulating and transmitted viruses and may play a role in reducing the infection rate in both adults and infants born to infected mothers, strategies based on 0.5g scFv or other anti-V3 antibodies could be particularly effective (7,11,19,29,39). In addition, combination of 0.5g scFv with certain CD4-mimetic compounds may deserve further investigation as the combination of KD-247 with certain CD4-mimetics markedly enhances the neutralization/binding activity in vitro (40).…”

M1 and M2a Polarization of Human Monocyte-Derived Macrophages Inhibits HIV-1 Replication by Distinct Mechanisms

“…contrast, expression of CCR5, the major coreceptor for macrophage-tropic strains of HIV-1, remained unchanged and, in some donors, was even up-regulated on the surface of M2a MDM vs M1 and controls. CXCR4, an entry coreceptor for X4-dependent viruses (which do not usually cause productive infection in MDM) (46,47), was also down-regulated in polarized MDM vs controls (Table I).…”

HIV-1-based defective lentiviral vectors efficiently transduce human monocytes-derived macrophages and suppress replication of wild-type HIV-1

“…Within a short time, they migrate into various tissues and mature into macrophages. These mononuclear cells also have the ability to cross the blood-brain barrier (BBB) and to enter the central nervous system (CNS), where they act as an important target and reservoir of HIV-1 [17][18][19][20][21]. HIV-1-infection of the brain can lead to HIV dementia, a primary disorder of the CNS, which affects nearly 25% of untreated, HIV-1-infected individuals [22].…”