A decline in CCL3-5 chemokine gene expression during primary simian-human immunodeficiency virus infection

Abstract

Background. The CC-chemokines CCL3, CCL4 and CCL5 have been found to bleck the entry of CCR5-tropic HIV into host cells and to suppress the viral replication in vitro, but the in vivo role of endogenous CC-chemokines in HIV-1 infection is still incompletely understood. Methodology/Principle Findings. In this study, the primate host CCL3, CCL4 and CCL5 gene expression was evaluated 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, a selected subset of samples from CXCR4-tropic SHIVKB1-infected macaques was included with objective to compare the differences in CC-chemokine down-regulation caused by the two SHIVs. Gut-associated lymphoid tissues (GALT) collected from SHIVSF152P4-infected animals were also tested by flow cytometry and confocal microscopy to corroborate the gene expression results. Predictably, highe r viral loads and CD4+ T cell losses were observed at PID 14 in macaques infected witv SHIVK41 than with SHIVSF362P4. A decline in CC-chemokine gene expression was also found during primary (PID 7-21), but not chronic (PID 180) stage of infection. Conclusions. It was determined that A) SHIVSF152P4 down-regulated the CC-chemokine gene expression during acute stage of infection to a greater extent (p<0.05) than SHIVKu1, and B) such down-regulation was not paralleled with the CD4+ T cell depletion. Evaluation of CC-chemokine enhancing immunomodulators such as synthetic CpG-oligonucleotides could be explored in future HIV vaccine studies. © 2007 Zhao et al.