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, SHIVSF162P, was compared with infection with the CXCR4 (X4)-specific SHIVSF33A.2. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIVSF162P caused a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion in peripheral CD4+ T cells, whereas infection with SHIVSF33A.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.

Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

“…The same comparisons of the other immunization groups (including the sCD4 group) versus the naive group revealed no significant differences in viral replication (P Ͼ 0.05 in all cases). In accordance with previous studies with SHIV 162P3 (27,28), there were no significant changes in the circulating percentage of CD3ϩCD4ϩ T cell levels in any of the challenged animals and no significant changes in this parameter between groups over time [supporting information (SI) Fig. 4].…”

A vaccine strategy against AIDS: An HIV gp41 peptide immunization prevents NKp44L expression and CD4 + T cell depletion in SHIV-infected macaques

“…injection of SHIV 162P3 , a CCR5-tropic virus. Profiles of viremia and CD4 count in SHIV162P3-infected cynomolgus macaques closely resembles naturally transmitted HIV strains in human patients (13,14). All animals immunized with 3S-KLH, initially at monthly intervals, developed much stronger immune responses against 3S, whereas the animals immunized with KLH alone did not (Fig.…”

“…with 1 ml of pooled plasma of cynomolgus macaques collected at peak of viremia during primary infection (days 12-17 postinfection) after intrarectal inoculation of pathogenic SHIV162P3, as described (13), obtained from the National Institutes of Health AIDS Research and Reference Reagent Program (catalog no. 6526).…”

Apoptosis in SIV infection

“…R5-tropic SHIV causes a dramatic loss of CD4 þ intestinal T cells and a gradual depletion in peripheral CD4 þ T cells, while infection with X4-tropic SHIV causes a profound loss in peripheral T cells that was not paralleled in the intestine. 174 Altogether, these reports suggest that the capacity to induce T-cell depletion in monkeys is a feature that depends at least in part on the genetic makeup of the envelope protein (X4 versus R5).…”