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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.
AuthorsErica L Johnson, Chanie L Howard, Joy Thurman, Kyle Pontiff, Elan S Johnson, Rana Chakraborty
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 211 Issue 2 Pg. 187-96 (Jan 15 2015) ISSN: 1537-6613 [Electronic] United States
PMID25081935 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Chemical References
  • CCR5 protein, human
  • Receptors, CCR5
Topics
  • Adult
  • CD4-Positive T-Lymphocytes (chemistry, immunology)
  • Cell Proliferation
  • Cells, Cultured
  • Cytomegalovirus (immunology)
  • Female
  • Fetal Blood (immunology)
  • Flow Cytometry
  • HIV Infections (transmission)
  • HIV-1 (physiology)
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical
  • Pregnancy
  • Receptors, CCR5 (analysis)

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