Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
The fate of molecularly cloned SIV in vivo: patterns of genetic evolution associated with AIDS.
Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:19 (abstract no. 3). Unique Identifier : AIDSLINE PRIM8/900003 Johnson PR; Hamm TE; Hirsch VM; Department of Microbiology, Georgetown University, and Laboratory; of Infectious Diseases, NIAID/NIH, Rockville, Md. 20852
Abstract:
One potential obstacle to the development of an effective AIDS vaccine is the inordinate genetic heterogeneity of HIV isolates. The basis for this genetic diversity appears to be the extreme plasticity of the HIV genome. Although highly informative, studies presented to date on the genetic variation of HIV-1 from infected humans have been limited (of necessity) by an incomplete knowledge of the genetic complexity of the transmitted virus inoculum and the precise time of infection. In the SIV model of AIDS, both of these limitations are removed. SIV derived from a single genetically-defined provirus can be used for experimental inoculation of macaques. Subsequently, the fate of a single SIV genome, as it replicates over time in the infected host, can be determined. To measure SIV genetic drift, we have studied four macaques infected with molecularly cloned SIV. Genomic DNA isolated from circulating leukocytes at 20 to 52 weeks after inoculation served as the template for PCR amplification of SIV sequences. Individual clones were selected, sequenced, and compared with the original clone. Two regions of the SIV genome were examined: the integrase domain of pol and the env gene. Our findings indicate that SIV is capable of rapid and extensive change in infected macaques, and that certain patterns of evolution appear to be associated with AIDS. Specifically, the data show that: (i) the env gene displays a tremendous capacity for divergence, with a frequency as high as 10(-1) nucleotide substitutions/ site/year; (ii) integrase incorporates changes less frequently (by an order of magnitude) than the env gene; (iii) the great majority of genomes in some animals contain multiple in-frame stop codons in the env gene; (iv) novel proviruses representing subgenomic spliced mRNAs (presumably generated by reverse transcription) are frequently detected in some animals; and, (v) the combined presence of env genes without in-frame stop codons and subgenomic spliced DNA transcripts appears to be associated with immunodeficiency and AIDS.
Keywords: Acquired Immunodeficiency Syndrome/*GENETICS Animal Cloning, Molecular DNA, Viral/BIOSYNTHESIS *Evolution Gene Frequency Genes, env Genes, pol Leukocytes/CHEMISTRY Macaca RNA Splicing RNA, Messenger/BIOSYNTHESIS Simian Acquired Immunodeficiency Syndrome/*GENETICS SIV/*GENETICS Terminator Regions (Genetics) Variation (Genetics) Virus Replication ABSTRACT 910730
M9170991
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
