In vivo adaptation of SHIVSF162: Chimeric virus expressing a NSI, CCR5‐specific envelope protein

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Abstract
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, SHIVSF162, containing the env, tat, rev, and vpu genes from HIV-1SF162 (R5, MT/NSI) in the context of the molecular clone simian immunodeficiency virus, SIVmac239. 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 SHIVSF162 (P1) had detectable levels of viral replication (as determined by p27gag 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 p27gag antigen. These results demonstrate that in vivo serial passage of the R5-specific SHIVSF162 enhanced its replicative capacity.