MOLECULAR-CLONING AND CHARACTERIZATION OF VIRUSES ISOLATED FROM CHIMPANZEES WITH PATHOGENIC HUMAN IMMUNODEFICIENCY - VIRUS TYPE-1 INFECTIONS

We have previously described the development of AIDS in a chimpanzee ( C499) infected with human immunodeficiency virus type 1 (HIV-1) and th e subsequent pathogenic HIV-1 infection in another chimpanzee (C455) t ransfused with blood from C499 (F. J. Novembre et al,, J. Virol. 71:40 86-4091, 1997). In the present study, two virus isolates were derived from these animals: HIV-1(JC) from peripheral blood mononuclear cells (PBMC) of C499, and HIV-1(NC) from plasma of C455. These virus isolate s were used to generate two infectious molecular clones, termed HIV-1( JC16) and HIV-1(NC7) (JC16 and NC7, respectively). Comparative analyse s of the sequences of the two dunes showed that they were highly inter related but distinct, Based on heteroduplex mobility assays, JC16 and NC7 appear to represent dominant viruses in the uncloned stock populat ion. Compared with amino acid sequences of the parental viruses HIV-1( SF2), HIV-1(LAV-1b), and HIV-1(NDK), JC16 and NC7 showed a number of d ifferences, including insertions, deletions, and point mutations sprea d throughout the genome. However, insertion/deletion footprints in sev eral genes of both JC16 and NC7 suggested that recombination between S F2 and LAV-1b could have occurred, possibly contributing to the genera tion of a pathogenic virus. Comparative in vitro analysts of the molec ular clones and the uncloned stocks of HIV-1(JC) and HIV-1(NC) reveale d that these viruses had strikingly similar replicative abilities in m itogen-stimulated PBMC and in macrophages, Compared to the SF2 and LAV -1b isolates of HIV-1, HIV-1(JC),, and HIV-1(NC) isolates were more si milar to LAV-1b with respect to the ability to replicate in mitogen-st imulated PBMC and macrophages. These viruses should prove to be useful in mapping determinants of pathogenesis.