HCMV enhances placental susceptibility and replication of HIV-1 which may facilitate in utero HIV-1 transmission.

Several co-pathogens that pose threats to the fetus during gestation, including human cytomegalovirus (HCMV), may also contribute MTCT of HIV-1. Within endemic settings, associations between maternal HCMV viral load and increased incidence of MTCT of HIV-1 are documented; however, the mechanisms that promote transmission are poorly characterized. Here we demonstrate that HCMV co-infection enhances susceptibility and viral replication of HIV-1 in placental macrophages (Hofbauer cells) in vitro. Consistent with enhanced viral susceptibility, HCMV exposure upregulates CCR5 and CD80 expression on Hofbauer cells. HCMV also significantly induces type-I interferon (IFN), pro-inflammatory cytokines, and antiviral gene expression. Interestingly, we found that HCMV diminishes type-I IFN-mediated phosphorylation of STAT2. Collectively, our data suggest that HCMV-induced activation, local inflammation, and antagonism of type-I IFN responses in placental Hofbauer cells, promotes in utero transmission of HIV-1.