Serial cervicovaginal exposures with replication-deficient SIVsm induce higher dendritic cell (pDC) and CD4+ T-cell infiltrates not associated with prevention but a more severe SIVmac251 infection of rhesus macaques.

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TitleSerial cervicovaginal exposures with replication-deficient SIVsm induce higher dendritic cell (pDC) and CD4+ T-cell infiltrates not associated with prevention but a more severe SIVmac251 infection of rhesus macaques.
Publication TypeJournal Article
Year of Publication2014
AuthorsAbdulhaqq, SA, Martinez, MI, Kang, G, Foulkes, AS, Rodriguez, IV, Nichols, SM, Hunter, M, Sariol, CA, Ruiz, LA, Ross, BN, Yin, X, Speicher, DW, Haase, AT, Marx, PA, Li, Q, Kraiselburd, EN, Montaner, LJ
JournalJ Acquir Immune Defic Syndr
Volume65
Issue4
Pagination405-13
Date Published2014 Apr 1
ISSN1944-7884
KeywordsAnimals, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Cervix Uteri, Dendritic Cells, Endometrium, Female, Macaca mulatta, Plasma, Simian Acquired Immunodeficiency Syndrome, Simian immunodeficiency virus, Vagina, Viral Load
Abstract

OBJECTIVE: Intravaginal exposure to simian immunodeficiency virus (SIV) acutely recruits interferon-alpha (IFN-α) producing plasmacytoid dendritic cells (pDC) and CD4 T-lymphocyte targets to the endocervix of nonhuman primates. We tested the impact of repeated cervicovaginal exposures to noninfectious, defective SIV particles over 72 hours on a subsequent cervicovaginal challenge with replication competent SIV.

METHODS: Thirty-four female Indian Rhesus macaques were given a 3-day twice-daily vaginal exposures to either SIVsmB7, a replication-deficient derivative of SIVsmH3 produced by a T lymphoblast CEMx174 cell clone (n = 16), or to CEM supernatant controls (n = 18). On the fourth day, animals were either euthanized to assess cervicovaginal immune cell infiltration or intravaginally challenged with SIVmac251. Challenged animals were tracked for plasma viral load and CD4 counts and euthanized at 42 days after infection.

RESULTS: At the time of challenge, macaques exposed to SIVsmB7, had higher levels of cervical CD123 pDCs (P = 0.032) and CD4 T cells (P = 0.036) than those exposed to CEM control. Vaginal tissues showed a significant increase in CD4 T-cell infiltrates (P = 0.048) and a trend toward increased CD68 cellular infiltrates. After challenge, 12 SIVsmB7-treated macaques showed 2.5-fold greater daily rate of CD4 decline (P = 0.0408), and viral load rise (P = 0.0036) as compared with 12 control animals.

CONCLUSIONS: Repeated nonproductive exposure to viral particles within a short daily time frame did not protect against infection despite pDC recruitment, resulting instead in an accelerated CD4 T-cell loss with an increased rate of viral replication.

DOI10.1097/QAI.0000000000000047
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID24226059
PubMed Central IDPMC3943721
Grant ListHHSN261200800001E / CA / NCI NIH HHS / United States
P30 AI 045008 / AI / NIAID NIH HHS / United States
P30 AI045008 / AI / NIAID NIH HHS / United States
P30 CA010815 / CA / NCI NIH HHS / United States
P30 CA10815 / CA / NCI NIH HHS / United States
P40 OD012217 / OD / NIH HHS / United States
P40 OD012217 / OD / NIH HHS / United States
P51 OD011104 / OD / NIH HHS / United States
R01 AI084142 / AI / NIAID NIH HHS / United States
R01 AI084142 / AI / NIAID NIH HHS / United States
R01 AI094603 / AI / NIAID NIH HHS / United States
R01 AI094603 / AI / NIAID NIH HHS / United States
R01 HL107196 / HL / NHLBI NIH HHS / United States
R01 HL107196 / HL / NHLBI NIH HHS / United States
T32 AI070099 / AI / NIAID NIH HHS / United States
T32 AI070099 / AI / NIAID NIH HHS / United States