Document 0736
 DOCN  M9650736
 TI    Maintenance of syncytium-inducing phenotype of HIV type 1 is associated
       with positively charged residues in the HIV type 1 gp120 V2 domain
       without fixed positions, elongation, or relocated N-linked glycosylation
       sites.
 DT    9605
 AU    Cornelissen M; Hogervorst E; Zorgdrager F; Hartman S; Goudsmit J; Human
       Retrovirus Laboratory, Academic Medical Centre, Amsterdam,; The
       Netherlands.
 SO    AIDS Res Hum Retroviruses. 1995 Oct;11(10):1169-75. Unique Identifier :
       AIDSLINE MED/96157204
 AB    The prevalence of HIV-1 sequences of the envelope domains V1V2 and V3
       was analyzed by RT-PCR amplification. Two distinct biological phenotypes
       of HIV-1 have been described: the nonsyncytium-inducing (NSI) phenotype,
       best characterized by the inability to infect MT-2 cells, and the
       syncytium-inducing phenotype (SI), with the ability to infect MT-2
       cells. Viral phenotype SI has been associated with HIV pathogenesis. The
       presence of positively charged amino acids at position 306 and 320 in
       the V3 domain of gp120 has been shown to be required for the support of
       the SI phenotype. In addition, V2 elongation and relocation of
       N-glycosylation sites were postulated to herald an NSI to SI phenotype
       switch. The present study was designed to assess the stability of an
       elongated V2 region with relocated N-glycosylation sites observed in SI
       isolates compared to NSI isolates. Eleven isolates with the SI phenotype
       and 19 isolates with the NSI phenotype were included in the study. Nine
       of the SI and 1 of the NSI isolates had a positively charged residue at
       position 306 or 320 (p < 0.001) in the V3 domain as assessed by direct
       sequencing of the viral RNA. In contrast, elongation and/or relocation
       of N-glycosylation sites of the V2 variable region were not found to be
       a consistent genetic feature of the SI phenotype. However, SI isolates
       had more positively charged amino acid residues in the hypervariable V2
       region compared with NSI isolates. In one of the two SI isolates lacking
       positively charged amino acids at positions 306 or 320 in the V3 loop an
       elongation of 26 amino acids with 4 additional N-linked glycosylation
       sites was observed in the V2 region. This is consistent with the theory
       that elongation of V2 may be transiently required for SI conversion.
       These results suggest that maintenance of the SI phenotype requires
       positively charged amino acids in V3 in the majority of the virus
       population, but not an elongated V2 region with added or relocated
       N-linked glycosylation sites. Although increased charged residues in the
       V2 region may contribute.
 DE    Amino Acid Sequence  Binding Sites  Cell Line  Giant Cells/VIROLOGY
       Glycosylation  Human  HIV Envelope Protein gp120/CHEMISTRY/*PHYSIOLOGY
       HIV-1/CHEMISTRY/*PATHOGENICITY  Molecular Sequence Data  Peptide
       Fragments/CHEMISTRY  Phenotype  Phylogeny  Structure-Activity
       Relationship  Support, Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).