Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes.
The genetic diversity of human immunodeficiency virus (HIV) is a major concern thought to impact on immunologic escape and eventual vaccine efficacy. Here, simple and rapid methods are described for the detection and estimation of genetic divergence between HIV strains on the basis of the observation that DNA heteroduplexes formed between related sequences have a reduced mobility in polyacrylamide gels proportional to their degree of divergence. Reliable phylogenetic subtypes were assigned for HIV-1 strains from around the world. Relationships between viruses were closest when derived from the same or epidemiologically linked individuals. When derived from epidemiologically unlinked individuals, the relationships between viruses in a given geographic region correlated with the length of time HIV-1 had been detected in the population and the number of strains initiating widespread infection. Heteroduplex mobility analysis thus provides a tool to expedite epidemiological investigations by assisting in the classification of HIV and is readily applicable to the screening and characterization of other infectious agents and cellular genes.
Delwart
E L
EL
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5402.
Shpaer
E G
EG
Louwagie
J
J
McCutchan
F E
FE
Grez
M
M
Rübsamen-Waigmann
H
H
Mullins
J I
JI
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000349:Africa; D001483:Base Sequence; D015023:Democratic Republic of the Congo; D004591:Electrophoresis, Polyacrylamide Gel; D015752:Genes, env; D014644:Genetic Variation; D015658:HIV Infections / Q000382:microbiology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009656:North America; D009692:Nucleic Acid Heteroduplexes; D010802:Phylogeny; D016133:Polymerase Chain Reaction
D009692:Nucleic Acid Heteroduplexes