Extensive variation of human immunodeficiency virus type-1 in vivo.
Genotypic variation among independent isolates of human immunodeficiency virus type-1 (HIV-1) is well known, but its molecular basis and biological consequences are poorly understood. We examined the genesis of molecular variation in HIV-1 by sequential virus isolations from two chronically infected individuals and analysis of recombinant HIV-1 genomic clones. In three different virus isolates full-length HIV-1 clones were identified and found to consist, respectively, of 17, 9 and 13 distinguishable, but highly-related, viral genotypes. Thirty-five viral clones derived from two HIV-1 isolates obtained from the same individual but 16 months apart showed progressive change, yet were clearly related. Similar changes in the HIV-1 genome did not occur in vitro during virus isolation and amplification. The results indicate that HIV-1 variation in vivo is rapid, that a remarkably large number of related but distinguishable genotypic variants evolve in parallel and coexist during chronic infection, and that 'isolates' of HIV-1, unless molecularly or biologically cloned, generally consist of complex mixtures of genotypically distinguishable viruses.
Saag
M S
MS
Department of Internal Medicine, University of Alabama, Birmingham 35294.
Hahn
B H
BH
Gibbons
J
J
Li
Y
Y
Parks
E S
ES
Parks
W P
WP
Shaw
G M
GM
D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D005838:Genotype; D006678:HIV / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011110:Polymorphism, Genetic
D004279:DNA, Viral