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

Abstract

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.

Epstein–Barr and cytomegalovirus DNA salivary shedding correlate with long‐term plasma HIV RNA detection in HIV‐infected men who have sex with men

“…Clinical and mechanistic experimental approaches will be necessary to resolve this: recently positivity in a simple CMV IgG test was an independent risk factor for severe non‐AIDS defining events in a cohort of 5,119 subjects [Lichtner et al, ]). In addition in an in vitro model stimulation of activated cord blood mononuclear cells with CMV antigens led to upregulation of T central memory cells and expression of chemokine receptor 5 [Johnson et al, ].…”

Partners in Crime: The Role of CMV in Immune Dysregulation and Clinical Outcome During HIV Infection

“…Several mechanisms could play a role including the following: (i) direct interaction between CMV-encoded regulatory proteins and the HIV long terminal repeat (LTR) region resulting in transactivation of viral gene expression [70, 71], (ii) enhanced HIV replication stimulated through a release of CMV-induced inflammatory cytokines and chemokines [72], (iii) upregulation of CCR5 expression in central memory T cells, which has been recently described in cord blood mononuclear cells exposed in vitro [73] and might be mediated by enhanced (CMV-induced) interferon production [74], and (iv) clonal expansion of HIV-infected T cells through CMV-induced inflammatory cytokines and chemokines [75]. This relationship between CMV and HIV has been widely documented in the genital tract, where presence of detectable CMV DNA has been repeatedly associated with increased genital shedding of HIV RNA [12, 13, 76–79] and with increased HIV transmission [11, 14, 76].…”

Human cytomegalovirus triggers the assembly of AIM2 inflammasome in THP‐1‐derived macrophages

“…On the contrary, morbidity and mortality are high in immunodeficient and immunosuppressed patients, as well as those with an immature immune system. Infection in these individuals may result in retinitis, encephalitis, hepatitis, jaundice, hearing damage, microcephaly, atherosclerosis, and congenital birth defects such as developmental growth restriction, sensorial deafness, and vision loss …”

“…Infection in these individuals may result in retinitis, encephalitis, hepatitis, jaundice, hearing damage, microcephaly, atherosclerosis, and congenital birth defects such as developmental growth restriction, sensorial deafness, and vision loss. [4][5][6][7][8][9] After a transitory lytic cycle, HCMV undergoes longstanding latency, a period when the virus maintains a quiescent status in cells of a myeloid lineage. 10 Exposure to HCMV triggers host innate and adaptive immune responses.…”