Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Child
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DNA, Viral
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Disease Transmission, Infectious*
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Evolution, Molecular*
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Female
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Gene Products, gag / genetics
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Genetic Variation
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Genotype
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HIV Antigens / genetics
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HIV Core Protein p24 / genetics
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HIV Envelope Protein gp120 / genetics*
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HIV Infections / blood
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HIV Infections / transmission
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HIV Infections / virology*
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HIV-1 / classification
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HIV-1 / genetics*
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HIV-1 / isolation & purification
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Humans
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Infectious Disease Transmission, Vertical*
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Leukocytes, Mononuclear / virology
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Male
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Molecular Sequence Data
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Peptide Fragments / genetics*
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Phylogeny
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Polymerase Chain Reaction
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Viral Proteins*
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gag Gene Products, Human Immunodeficiency Virus
Substances
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DNA, Viral
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Gene Products, gag
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HIV Antigens
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HIV Core Protein p24
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HIV Envelope Protein gp120
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HIV envelope protein gp120 (305-321)
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Peptide Fragments
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Viral Proteins
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gag Gene Products, Human Immunodeficiency Virus
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p17 protein, Human Immunodeficiency Virus Type 1
Associated data
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GENBANK/AB014775
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GENBANK/AB014776
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GENBANK/AB014777
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GENBANK/AB014778
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GENBANK/AB014779
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GENBANK/AB014780
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GENBANK/AB014781
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GENBANK/AB014782
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GENBANK/AB014783
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GENBANK/AB014784
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GENBANK/AB014785
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GENBANK/AB014786
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GENBANK/AB014787
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GENBANK/AB014788
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GENBANK/AB014789
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GENBANK/AB014790
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GENBANK/AB014791
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GENBANK/AB014792
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GENBANK/AB014793
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GENBANK/AB014794
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GENBANK/AB014795
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GENBANK/AB014796
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GENBANK/AB014797
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GENBANK/AB014798
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GENBANK/AB014799
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GENBANK/AB014800
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GENBANK/AB014801
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GENBANK/AB014802
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GENBANK/AB014803
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GENBANK/AB014804