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Journal of Virology, May 1999, p. 3551-3559, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Hironori Sato,1,* Teiichiro Shiino,1 Noriko Kodaka,1 Kiyomi Taniguchi,2 Yasuhiro Tomita,3 Kayoko Kato,1 Tuyoshi Miyakuni,4 and Yutaka Takebe1

Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo 162-8640,1 Division of Pathology, National Institute of Infectious Diseases, Tokyo,2 Faculty of Agriculture, Iwate University, Iwate,3 and Naha Prefectural Hospital, Yogi 1-3-1, Naha, Okinawa 902-0076,4 Japan

Received 27 April 1998/Accepted 19 January 1999

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.

* 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)-3-52851111. Fax: (81)-3-52851177. E-mail: hirosato{at}nih.go.jp

Journal of Virology, May 1999, p. 3551-3559, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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