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Journal of Virology, February 2000, p. 1069-1078, Vol. 74, No. 3
Laboratory of Molecular Virology and
Epidemiology, AIDS Research Center, National Institute of Infectious
Diseases, Shinjuku, Tokyo 162-8640,1 and
Naha Prefectural Hospital, Naha, Okinawa
902,2 Japan
Received 19 May 1999/Accepted 25 October 1999
In a human immunodeficiency virus type 1 (HIV-1)-infected
individual, immune-pressure-mediated positive selection operates to
maintain the antigenic polymorphism on the gp120 third variable (V3)
loop. Recently, we suggested on the basis of sequencing C2/V3 segments
from an HIV-1 subtype E-infected family that a V3 sequence lineage
group of the non-syncytium-inducing (NSI) variants (group 1) was
relatively resistant to positive selection pressure (35). To
better understand the relationship between the intensity of positive
selection pressure and cell tropism of the virus, we determined the
linkage between each V3 genotype and its function of directing
coreceptor preference and MT2 cell tropism. The biological characterization of a panel of V3 recombinant viruses showed that all
of the group 1 V3 sequences could confer an NSI/CCR5-using (NSI/R5)
phenotype on HIV-1LAI, whereas the group 2 V3 sequence, which was more positively charged than the group 1 sequence, dictated mainly a syncytium-inducing, CXCR4-using (SI/X4) phenotype.
Phylogenetic analysis of C2/V3 sequences encoding group 1 or 2 V3
suggested that the variants carrying group 1 V3 are the ancestors of
the intrafamilial infection and persisted in the family, while the variants carrying group 2 V3 evolved convergently from the group 1 V3
variants during disease progression in the individuals. Finally, a
statistical test showed that the V3 sequence that could dictate an
NSI/R5 phenotype had a synonymous substitution rate significantly higher than the nonsynonymous substitution rate. These data suggest that V3 sequences of the subtype E NSI/R5 variants are more resistant to positive selection pressure than those of the SI/X4 variants.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A Group of V3 Sequences from Human Immunodeficiency
Virus Type 1 Subtype E Non-Syncytium-Inducing, CCR5-Using Variants
Are Resistant to Positive Selection Pressure
*
Corresponding author. Mailing address: Laboratory of
Molecular Virology and Epidemiology, AIDS Research Center, National
Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo
162-8640, Japan. Phone: (81-3) 5285-1111. Fax: (81-3) 5285-1177. E-mail: tshiino{at}nih.go.jp.
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