TY - JOUR
T1 - Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection
AU - Abel, Kristina
AU - Rocke, David M
AU - Chohan, Barinderpal
AU - Fritts, Linda
AU - Miller, Chris J
PY - 2005/10
Y1 - 2005/10
N2 - The current knowledge about early innate immune responses at mucosal sites of human immunodeficiency vires (HIV) entry is limited but likely to be important in the design of effective HIV vaccines against heterosexual transmission. This study examined the temporal and anatomic relationship between vires replication, lymphocyte depletion, and cytokine gene expression levels in mucosal and lymphoid tissues in a vaginal-transmission model of HIV in rhesus macaques. The results of the study show that the kinetics of cytokine gene expression levels in the acute phase of infection are positively correlated with virus replication in a tissue. Thus, cytokine responses after vaginal simian immunodeficiency virus (SIV) inoculation are earliest and strongest in mucosal tissues of the genital tract and lowest in systemic lymphoid tissues. Importantly, the early cytokine response was dominated by the induction of proinflaminatory cytokines, while the induction of cytokines with antiviral activity, alpha/beta interferon, occurred too late to prevent virus replication and dissemination. Thus, the early cytokine response favors immune activation, resulting in the recruitment of potential target cells for SIV. Further, unique cytokine gene expression patterns were observed in distinct anatomic locations with a rapid and persistent inflammatory response in the gut tbat is consistent with the gut being the major site of early CD4 T-cell depletion in SIV infection.
AB - The current knowledge about early innate immune responses at mucosal sites of human immunodeficiency vires (HIV) entry is limited but likely to be important in the design of effective HIV vaccines against heterosexual transmission. This study examined the temporal and anatomic relationship between vires replication, lymphocyte depletion, and cytokine gene expression levels in mucosal and lymphoid tissues in a vaginal-transmission model of HIV in rhesus macaques. The results of the study show that the kinetics of cytokine gene expression levels in the acute phase of infection are positively correlated with virus replication in a tissue. Thus, cytokine responses after vaginal simian immunodeficiency virus (SIV) inoculation are earliest and strongest in mucosal tissues of the genital tract and lowest in systemic lymphoid tissues. Importantly, the early cytokine response was dominated by the induction of proinflaminatory cytokines, while the induction of cytokines with antiviral activity, alpha/beta interferon, occurred too late to prevent virus replication and dissemination. Thus, the early cytokine response favors immune activation, resulting in the recruitment of potential target cells for SIV. Further, unique cytokine gene expression patterns were observed in distinct anatomic locations with a rapid and persistent inflammatory response in the gut tbat is consistent with the gut being the major site of early CD4 T-cell depletion in SIV infection.
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U2 - 10.1128/JVI.79.19.12164-12172.2005
DO - 10.1128/JVI.79.19.12164-12172.2005
M3 - Article
C2 - 16160143
AN - SCOPUS:25144479948
VL - 79
SP - 12164
EP - 12172
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 19
ER -