Abstract
SIV or SHIV infection of nonhuman primates (NHP) has been used to investigate the impact of coreceptor usage on the composition and dynamics of the CD4+ T cell compartment, mechanisms of disease induction and development of clinical syndrome. As the entire course of infection can be followed, with frequent access to tissue compartments, infection of rhesus macaques with CCR5-tropic SHIVs further allows for study of HIV-1 coreceptor switch after intravenous and mucosal inoculation, with longitudinal and systemic analysis to determine the timing, anatomical sites and cause for the change in envelope glycoprotein and coreceptor preference. Here, we review our current understanding of coreceptor use in NHPs and their impact on the pathobiological characteristics of the infection, and discuss recent advances in NHP studies to uncover the underlying selective pressures for the change in coreceptor preference in vivo.
Highlights
Animal models have always been considered powerful tools for studying the modality of transmission and pathogenesis of human diseases, and for testing the efficacy of novel drugs and vaccines
Concluding remarks simian immunodeficiency viruses (SIVs) and SIV and HIV sequences (SHIVs) infection of RMs provide experimentally attractive models to study the impact of coreceptor usage on viral replication, CD4 T cell depletion and disease
The conditions, phenotypic characteristics as well as envelope V3 sequences required for coreceptor switch in R5 SHIV infected macaques overlap with those reported in HIV-1 infected individuals, supporting the use of this model to study the mechanistic basis and selective forces for HIV-1 coreceptor switching in vivo
Summary
Animal models have always been considered powerful tools for studying the modality of transmission and pathogenesis of human diseases, and for testing the efficacy of novel drugs and vaccines. The conditions, phenotypic characteristics as well as envelope V3 sequences required for coreceptor switch in R5 SHIV infected macaques overlap with those reported in HIV-1 infected individuals, supporting the use of this model to study the mechanistic basis and selective forces for HIV-1 coreceptor switching in vivo While this phenomenon has so far been documented only in a small number of R5 SHIV infected RPs who fail to mount or sustain virus-specific antibody response, studies of these animals are still important, for they allow examination of the process of a generalized switch uncomplicated by the selection pressure of antiviral immune responses. The model could be improved by examining the process of coreceptor switching in genetically-defined R5 SHIV infected rhesus monkeys that have developed a neutralizing antibody response, to discern the impact of innate and adaptive immune selection forces on the evolutionary pathways available for tropism switch
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