TY - JOUR
T1 - 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
AU - Abdulhaqq, Shaheed A.
AU - Martinez, Melween I.
AU - Kang, Guobin
AU - Foulkes, Andrea S.
AU - Rodriguez, Idia V.
AU - Nichols, Stephanie M.
AU - Hunter, Meredith
AU - Sariol, Carlos A.
AU - Ruiz, Lynnette A.
AU - Ross, Brian N.
AU - Yin, Xiangfan
AU - Speicher, David W.
AU - Haase, Ashley T
AU - Marx, Preston A.
AU - Li, Qinsheng
AU - Kraiselburd, Edmundo N.
AU - Montaner, Luis J.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Objective: Intravaginal exposure to simian immunodeficiency virus (SIV) acutely recruits interferon-alpha (IFN-a) 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 replicationdeficient 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.
AB - Objective: Intravaginal exposure to simian immunodeficiency virus (SIV) acutely recruits interferon-alpha (IFN-a) 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 replicationdeficient 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.
KW - CD4
KW - Cervicovaginal mucosa
KW - Nonhuman primate
KW - Plasmacytoid dendritic cells
KW - Simian immunodeficiency virus
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U2 - 10.1097/QAI.0000000000000047
DO - 10.1097/QAI.0000000000000047
M3 - Article
C2 - 24226059
AN - SCOPUS:84898010829
SN - 1525-4135
VL - 65
SP - 405
EP - 413
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 4
ER -