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Title: Syncytium-Inducing and Non-Syncytium-Inducing Capacity of Human Immunodeficiency Virus Type 1 Subtypes other Than B: Phenotypic and Genotypic Characteristics
Authors: Frank de Wolf
Els Hogervorst
Jaap Goudsmit
Eva Maria Fenyö
Helga Rübsamen-Waigmann
Harvey Holmes
Bernardo Galvao-Castro
Etienne Karita
Chantapong Wasi
S. D.K. Sempala
Elly Baan
Fokla Zorgdrager
Vladimir Lukashov
Saladin Osmanov
Carla Kuiken
Marion Cornelissen
University of Amsterdam
Karolinska University Hospital
Bayer AG
National Institute for Biological Standards and Control
Reference Laboratory of the Brazilian Network on HIV Isolation and Characterization
National AIDS Control Program Rwanda
Mahidol University
Uganda Virus Research Institute
Organisation Mondiale de la Sante
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Jan-1994
Citation: AIDS Research and Human Retroviruses. Vol.10, No.11 (1994), 1387-1400
Abstract: Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B. © 1994, Mary Ann Liebert, Inc. All rights reserved.
ISSN: 19318405
Appears in Collections:Scopus 1991-2000

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