Evolution and biological characterization of human immunodeficiency virus type 1 subtype E gp120 V3 sequences following horizontal and vertical virus transmission in a single family.
It has been suggested that immune-pressure-mediated positive selection operates to maintain the antigenic polymorphism on the third variable (V3) loop of the gp120 of human immunodeficiency virus type 1 (HIV-1). Here we present evidence, on the basis of sequencing 147 independently cloned env C2/V3 segments from a single family (father, mother, and their child), that the intensity of positive selection is related to the V3 lineage. Phylogenetic analysis and amino acid comparison of env C2/V3 and gag p17/24 regions indicated that a single HIV-1 subtype E source had infected the family. The analyses of unique env C2/V3 clones revealed that two V3 lineage groups had evolved in the parents. Group 1 was maintained with low variation in all three family members regardless of the clinical state or the length of infection, whereas group 2 was only present in symptomatic individuals and was more positively charged and diverse than group 1. Only virus isolates carrying the group 2 V3 sequences infected and induced syncytia in MT2 cells, a transformed CD4(+)-T-cell line. A statistically significant excess of nonsynonymous substitutions versus synonymous substitutions was demonstrated only for the group 2 V3 region. The data suggest that HIV-1 variants, possessing the more homogeneous group 1 V3 element and exhibiting the non-syncytium-inducing phenotype, persist in infected individuals independent of clinical status and appear to be more resistant to positive selection pressure.
Sato
H
H
Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo 162-8640, Japan. hirosato@nih.go.jp
Shiino
T
T
Kodaka
N
N
Taniguchi
K
K
Tomita
Y
Y
Kato
K
K
Miyakuni
T
T
Takebe
Y
Y
D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D004279:DNA, Viral; D018562:Disease Transmission, Infectious; D019143:Evolution, Molecular; D005260:Female; D015683:Gene Products, gag / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D015488:HIV Antigens / Q000235:genetics; D016655:HIV Core Protein p24 / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000097:blood / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1