A DECLINE IN CC-CHEMOKINE GENE EXPRESSION DURING PRIMARY SHIV INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The CC-chemokines CCL3, CCL4 and CCL5 have been found to block the entry of CCR5-tropic HIV into host cells and to suppress the viral replication in vitro. Main objective of this study was to evaluate the host CCL3, CCL4 and CCL5 gene expression in response to simian-human immunodeficiency virus (SHIV) infection in rhesus macaque model. Five rhesus macaques were inoculated with CCR5-tropic SHIVSF162P4. The mRNA levels of CCL3, CCL4 and CCL5 were measured by real-time PCR at post inoculation day (PID) 0, 7, 14, 21, 35, 56 and 180 in peripheral blood. In addition, gut-associated lymphoid tissues (GALT) e.g. jejunum, colon and mesenteric lymph nodes (MLN) collected at PID 0, 14 and 180 were tested. Plasma viral loads and peripheral blood CD4+ T cell counts were used as indicators of the viral infection. A decline in CC-chemokine gene expression was found during primary (PID 7-21), but not during chronic (PID 180) stage of infection. The lowest gene expression levels at PID 14 coincided with the peak of viremia. Compared with PID 0, expressions of all three CC-chemokines were decreased (p0.05) at PID14 in peripheral blood. Moreover, CCL3 and CCL4 were decreased (p0.05) at PID 14 in all three GALTs. Gene expression results were corroborated by flow cytometry and confocal microscopy. Decline of CC-chemokine production during primary SHIV infection may thus facilitate further spread of the virus.