CD8+ T cell-mediated CXC chemokine receptor 4-simian/human immunodeficiency virus suppression in dually infected rhesus macaques.
We coinfected rhesus macaques with CXC chemokine receptor 4- and CC chemokine receptor 5-specific simian/human immunodeficiency viruses (SHIVs) to elucidate the basis for the early dominance of R5-tropic strains seen in HIV-infected humans. We found no intrinsic barrier to the transmission and dissemination of high-dose X4-SHIV in the dually infected macaques. In animals that maintained a viral set point, the R5 virus predominated. The time of appearance of R5 dominance coincided with the development of virus-specific immunity (3-6 weeks postinfection), suggestive of differential immune control of the two viruses. Indeed, after depletion of CD8+ T cells in the coinfected animals, X4 virus emerged, supporting the concept that differential CD8+ T cell-mediated immune control of X4- and R5-SHIV replication is responsible for the selective outgrowth of R5 viruses. These findings provide critical insights into a key question related to HIV pathogenesis and have important implications for the development and testing of antiviral vaccines and therapeutics.
Harouse
Janet M
JM
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, 7th Floor, New York, NY 10016, USA. jharouse@adarc.org
Buckner
Clarisa
C
Gettie
Agegnehu
A
Fuller
Ross
R
Bohm
Rudolf
R
Blanchard
James
J
Cheng-Mayer
Cecilia
C
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006678:HIV / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D019718:Receptors, CXCR4 / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
D012367:RNA, Viral; D019718:Receptors, CXCR4