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 macrophage inflammatory protein (MIP)-1beta has been previously found to block the entry of CCR5-tropic human immunodeficiency virus (HIV) into host cells and to suppress the viral replication in vitro. This study objective was the evaluation of MIP-1beta and selected cytokine genes expression during primary stage of in vivo infection with CCR5- and CXCR4-tropic simian-HIV (SHIV). Five rhesus macaques (Macaca mulatta) were inoculated with CCR5-tropic SHIVSF162P4 and another five with CXCR4-tropic SHIVKu1. Five macaques previously infected with highly pathogenic simian immunodeficiency virus (SIV)mac239, exhibiting the symptoms of simian AIDS (SAIDS) served as late stage infection controls. The expression of MIP-1beta and selected cytokine genes was evaluated. In addition, viral loads and CD4+ T cell counts were measured in peripheral blood. A decline in MIP-1beta gene expression was found in peripheral blood and gut-associated lymphoid tissues (GALT) at post inoculation day (PID) 14 of SHIVSF162P4 and SHIVKu1 infected macaques (p0.05), but not at the terminal stage of infection in SAIDS animals. The lowest MIP-1beta gene expression level at PID 14 coincided with the peak of viremia. The expressions of IL-2, IL-6 and IL-12 was also significantly decreased. Greater extent of MIP-1beta down-regulation was observed in macaques infected with less pathogenic CCR5-tropic SHIVSF162P4 than with CXCR4-tropic SHIVKu1 (p0.05). We conclude that MIP-1beta down-regulation is not driven solely by CD4+ T cell depletion but it is linked to different chemokine co-receptors that are used by mucosa- and systemic-tropic SHIVs to enter the host cell.
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