An infectious molecular clone was derived from the HIV-2(UC2) isolate that previously was found to persistently infect and induce an AIDS-like disease syndrome in baboons. The molecularly cloned virus (HIV-2(UC2mc)) showed in vitro properties similar to those of the parental isolate with regard to T-cell tropism, cytopathicity, and the ability to infect primary baboon PBMC. Nevertheless, when inoculated into two baboons, the cloned virus showed a limited ability to replicate in these animals. DNA sequence analysis revealed a defective vpr gene in the UC2mc as well as in the pathogenic parental UC2 strain. Thus, the vpr gene is not required for the induction of disease in baboons. The attenuated infectious molecular clone of UC2 should be useful for future studies designed to map the genetic determinants of HIV-2 pathogenesis in the baboon model and to evaluate vaccine strategies.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health Grant AI24286-05 and University of California Universitywide AIDS Research Program Grant R90SF213. S.W.B. was a Scholar of the American Foundation for AIDS Research. D.J.B. was supported by the University of California, Universitywide AIDS Research Program Grant F94-SF-006. C.P.L. was the recipient of a postdoctoral grant from the George M. Hooper Foundation, UCSF. Special thanks to Roger Wang at Chiron Corp. for DNA sequencing, Kersti MacInnes at Los Alamos National Laboratory for the phylogenetic analyses, and to Graham Redgrave at UCSF for help with the Fasta analysis. We also thank Chris Beglinger for help in preparation of the manuscript. The entire proviral DNA sequence of UC2mc was deposited in GenBank (Accession No. U38293).