Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs.
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.
Harouse
J M
JM
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, 7th Floor, New York, NY 10016, USA.
Gettie
A
A
Tan
R C
RC
Blanchard
J
J
Cheng-Mayer
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002678:Chimera; D003106:Colon / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology; D007583:Jejunum / Q000276:immunology; D008253:Macaca mulatta; D016865:Reassortant Viruses; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication
D019713:Receptors, CCR5; D019718:Receptors, CXCR4