Distinct Pathogenic Sequela in Rhesus Macaques Infected with CCR5 or CXCR4 Utilizing SHIVs

Abstract

Infection of macaques with chimeric simian–human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)–specific enveloped virus, SHIV SF162P , was compared with infection with the CXCR4 (X4)–specific SHIV SF33A.2 . Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIV SF162P caused a dramatic loss of CD4 + intestinal T cells followed by a gradual depletion in peripheral CD4 + T cells, whereas infection with SHIV SF33A.2 caused a profound loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.