Erica L Johnson1, Rana Chakraborty. 1. aDepartment of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine bChildren's Center for Immunology and Vaccines, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Abstract
PURPOSE OF REVIEW: Mother-to-child transmission (MTCT) of HIV-1 remains a significant global health concern despite implementation of maternal combination antiretroviral therapy for treatment as prevention to offset transmission. The risk of in-utero HIV-1 transmission in the absence of interventions is ∼7%. This low rate of transmission points to innate and adaptive mechanisms to restrict lentiviral infection within the placenta. RECENT FINDINGS: Placental macrophages (Hofbauer cells) are key mediators in in-utero transmission of HIV-1. Hofbauer cells constitutively express elevated concentrations of regulatory cytokines, which inhibit HIV-1 replication in vitro, and possess intrinsic antiviral properties. Hofbauer cells sequester HIV-1 in intracellular compartments that can be accessed by HIV-1-specific antibodies and may occur in vivo to offset MTCT. Intriguingly, studies have reported strong associations between maternal human cytomegalovirus (HCMV) viremia and MTCT of HIV-1. HCMV infection at the placenta promotes inflammation, chronic villitis, and trophoblast damage, providing potential HIV-1 access into CD4CCR5 target cells. The placenta exhibits a variety of mechanisms to limit HIV-1 replication, yet viral-induced activation with maternal HCMV may override this protection to facilitate in-utero transmission of HIV-1. SUMMARY: Understanding immune correlates of protection or transmission at the placenta during on-going HIV-1 exposure may contribute to understanding HIV pathogenesis and the development of effective immunotherapies.
PURPOSE OF REVIEW: Mother-to-child transmission (MTCT) of HIV-1 remains a significant global health concern despite implementation of maternal combination antiretroviral therapy for treatment as prevention to offset transmission. The risk of in-utero HIV-1 transmission in the absence of interventions is ∼7%. This low rate of transmission points to innate and adaptive mechanisms to restrict lentiviral infection within the placenta. RECENT FINDINGS: Placental macrophages (Hofbauer cells) are key mediators in in-utero transmission of HIV-1. Hofbauer cells constitutively express elevated concentrations of regulatory cytokines, which inhibit HIV-1 replication in vitro, and possess intrinsic antiviral properties. Hofbauer cells sequester HIV-1 in intracellular compartments that can be accessed by HIV-1-specific antibodies and may occur in vivo to offset MTCT. Intriguingly, studies have reported strong associations between maternal human cytomegalovirus (HCMV) viremia and MTCT of HIV-1. HCMVinfection at the placenta promotes inflammation, chronic villitis, and trophoblast damage, providing potential HIV-1 access into CD4CCR5 target cells. The placenta exhibits a variety of mechanisms to limit HIV-1 replication, yet viral-induced activation with maternal HCMV may override this protection to facilitate in-utero transmission of HIV-1. SUMMARY: Understanding immune correlates of protection or transmission at the placenta during on-going HIV-1 exposure may contribute to understanding HIV pathogenesis and the development of effective immunotherapies.
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