Editors choice: Cytomegalovirus Upregulates Expression of CCR5 in Central Memory Cord Blood Mononuclear Cells Which May Facilitate In Utero HIV Type 1 Transmission

摘要

Administration of combination antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)–infected pregnant women significantly reduces vertical transmission. In contrast, maternal co-opportunistic infection with primary or reactivated cytomegalovirus (CMV) or other pathogens may facilitate in utero transmission of HIV-1 by activation of cord blood mononuclear cells (CBMCs). Here we examine the targets and mechanisms that affect fetal susceptibility to HIV-1 in utero. Using flow cytometry, we demonstrate that the fraction of CD4⁺CD45RO⁺ and CD4⁺CCR5⁺ CBMCs is minimal, which may account for the low level of in utero HIV-1 transmission. Unstimulated CD4⁺ CBMCs that lack CCR5/CD45RO showed reduced levels of HIV-1 infection. However, upon in vitro stimulation with CMV, CBMCs undergo increased proliferation to upregulate the fraction of T central memory cells and expression of CCR5, which enhances susceptibility to HIV-1 infection in vitro. These data suggest that activation induced by CMV in vivo may alter CCR5 expression in CD4⁺ T central memory cells to promote in utero transmission of HIV-1.