In vivo adaptation of SHIV(SF162): chimeric virus expressing a NSI, CCR5-specific envelope protein.
The chemokine receptor CCR5 is known to be a critical determinant of human immunodeficiency virus (HIV) transmission and pathogenesis in the human host. Towards the development of a macaque model to evaluate the efficacy of vaccines and therapeutics against infection with CCR5-specific viruses, and to delineate the pathogenic properties of such viruses, we constructed a chimeric simian human immunodeficiency virus, SHIV(SF162), containing the env, tat, rev, and vpu genes from HIV-1(SF162) (R5, MT/NSI) in the context of the molecular clone simian immunodeficiency virus, SIV(mac239). Virus generated from this molecular clone was used to intravenously infect two juvenile macaques, followed by three consecutive serial blood/bone marrow transfusions. Animals infected with parental SHIV(SF162) (P1) had detectable levels of viral replication (as determined by p27(gag) production) within days of infection; however, viral set-points fell below detection by Week 3. Late passage animals (P3 and P4) had a two-log increase in the level of plasma p27(gag) antigen. These results demonstrate that in vivo serial passage of the R5-specific SHIV(SF162) enhanced its replicative capacity.
Tan
R C
RC
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
Harouse
J M
JM
Gettie
A
A
Cheng-Mayer
C
C
D016915:AIDS Vaccines; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002678:Chimera; D004195:Disease Models, Animal; D006801:Humans; D008253:Macaca mulatta / Q000276:immunology; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics*
D016915:AIDS Vaccines; D000956:Antigens, Viral; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D014759:Viral Envelope Proteins