Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype

Kuiken, Carla; Jong, J J de; Baan, Elly; Keulen, Wilco; Tersmette, M.; Goudsmit, Jaap

doi:10.1128/jvi.66.7.4622-4627.1992

Cited by 159 publications

(74 citation statements)

References 13 publications

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“…The hypervariable domains, designated V1 through V5, are interspersed with conserved regions along the gp120 molecule (20,22,33). Sequence variation in the env gene can affect the biological phenotype with respect to the replication rate in different cells, as well as cytotropism and the capacity to induce syncytia in vitro (4,5,8,13,15,23,24,26,35).…”

mentioning

confidence: 99%

Relationship of HIV‐1 Envelope V2 and V3 Sequences of the Primary Isolates to the Viral Phenotype

Yoshimura

Matsushita

Hayashi

et al. 1996

Microbiology and Immunology

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We examined the relationship between the amino acid sequences of the V2 and V3 regions of the envelope protein and the biological properties of ten human immunodeficiency virus type 1 (HIV-1) primary isolates. The infectivity, cytopathic effect (CPE), and syncytium forming activity of these primary isolates were tested against three T cell lines (CEM, MT2, and MOLT4/CL.8 cells), CD8-depleted peripheral blood mononuclear cells (PBMC), and primary monocyte-derived macrophages (MDM) from seronegative donors. In addition to the viral groups which had the syncytium inducing/T-cell line tropic (SI/TT) phenotype or non-syncytium inducing/non-T cell line tropic (NSI/NT) phenotype (including the NSI/macrophage tropic (NSI/MT) phenotype), there was a group of viruses that infected one or two T cell lines and PBMC but could not mediate syncytium formation. We therefore classified this group of viruses as a non-syncytium inducing/partial T-cell line tropic (NSI/pTT) virus. To investigate the relationship between these viral phenotypes and the sequence variability of the V2 and V3 regions of the envelope, we cloned the viral gene segment and sequenced the individual isolates. The sequence data suggested that the SI/TT type changes in the V3 sequence alone mediate a partial T cell line tropism and mild cytopathic effect and that an isolate became more virulent (SI/TT phenotype) if there were additional changes in the V2 or other regions. On the other hand, sequence changes in the V2 region alone could not mediate phenotypic changes but some additional changes in the other variable regions (for example, V3) might be required for the phenotypic changes in combination with changes in V2. These findings also suggested that amino acid changes in both the V2 and V3 region are required for the development of virulent variants of HIV-1 that outgrow during advanced stages of the disease.Key words: Human immunodeficiency virus type 1 (HIV-1), Primary isolates, V2 and V3 sequences, Viral phenotype Genetic variability within the human immunodeficiency virus type 1 (HIV-1) genome is most pronounced in the env gene, in which nucleotide substitutions, duplications, and deletions produce extensive amino acid diversity within five hypervariable domains in the envelope glycoprotein. The hypervariable domains, designated V1 through V5, are interspersed with conserved regions along the gp120 molecule (20,22,33). Sequence variation in the env gene can affect the biological phenotype with respect to the replication rate in different cells, as well as cytotropism and the capacity to induce syncytia in vitro (4,5,8,13,15,23,24,26,35).A comparative analysis of a large set of V3 sequences derived from primary or culture-adapted isolates revealed that an acidic amino acid or alanine predominates at position 25 among the macrophage tropic isolates, whereas a basic or neutral amino acid at this site is associated with non-conservative basic amino acid substitutions mainly at positions 11, 24, and 32 and that both features correlate with the T c...

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mentioning

confidence: 99%

Relationship of HIV‐1 Envelope V2 and V3 Sequences of the Primary Isolates to the Viral Phenotype

Yoshimura

Matsushita

Hayashi

et al. 1996

Microbiology and Immunology

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“…In addition, strains recovered from an individual early during the course of infection differ from those isolated from the same individual at a later time, when disease has developed. Among the properties of HIV-1 that have been shown to change over time in infected individuals are efficiency of viral replication in vitro, differential tropism for macrophages and T-cell lines, and ability to induce syncytium formation in T-cell lines (13,20,26,30,37,40,48). The genetic determinants of these biological properties of HIV-1 have been localized primarily to the V3 region of the env gene.…”

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confidence: 99%

Convergent evolution within the V3 loop domain of human immunodeficiency virus type 1 in association with disease progression

Strunnikova

Ray

Livingston

et al. 1995

J Virol

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Phylogenetic analysis was used to study in vivo genetic variation of the V3 region of human immunodeficiency virus type 1 in relation to disease progression in six infants with vertically acquired human immunodeficiency virus type 1 infection. Nucleotide sequences from each infant formed a monophyletic group with similar average branch lengths separating the sets of sequences. In contrast to the star-shaped phylogeny characteristic of interinfant viral evolution, the shape of the phylogeny formed by sequences from the infants who developed AIDS tended to be linear. A computer program, DISTRATE, was written to analyze changes in DNA distance values over time. For the six infants, the rate of divergence from the initial variant was inversely correlated with CD4 cell counts averaged over the first 11 to 15 months of life (r ‫؍‬ ؊0.87, P ‫؍‬ 0.024). To uncover evolutionary relationships that might be dictated by protein structure and function, tree-building methods were applied to inferred amino acid sequences. Trees constructed from the full-length protein fragment (92 amino acids) showed that viruses from each infant formed a monophyletic group. Unexpectedly, V3 loop protein sequences (35 amino acids) that were found at later time points from the two infants who developed AIDS clustered together. Furthermore, these sequences uniquely shared amino acids that have been shown to confer a T-cell line tropic phenotype. The evolutionary pattern suggests that viruses from these infants with AIDS acquired similar and possibly more virulent phenotypes.

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“…The``C3'' region and the V1-V2 bridge gradually accumulated mutations over time. As this pattern is similar to the V3 loop of HIV-1 [Kuiken et al, 1992], these two domains represent putative neutralization epitopes. In contrast, the V1 and V2 regions appear to be cycling since identical amino acid sequences can be identi®ed at several months' intervals without being present in the intervening isolates.…”

Section: Discussionmentioning

confidence: 66%

Genetic variability of the V1 and V2 env domains of SIVcpz‐ant and neutralization pattern of plasma viruses in a chimpanzee infected naturally

Ondoa¹,

Davis²,

Willems³

et al. 2001

Journal of Medical Virology

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Specific neutralizing epitope changes have been observed in a chimpanzee infected naturally with SIVcpz, which differ from HIV-1 infecting humans. To characterize further these changes, a longitudinal study of env genomic sequence variation of SIVcpz-ant isolates was undertaken in this animal. The V1 and V2 regions of the env were determined to arise from specific recombination events. To determine whether recombination of the V1 and V2 domains was possibly associated with the emergence of neutralization escape viruses, envelope sequences and gene length polymorphisms from PBMC and plasma viral variants were studied over a 7-year period. PBMCs and plasma-associated infectious virus titers as well as plasma RNA viral loads were monitored longitudinally. The first 5 viruses isolated from the plasma were found to be neutralization escape variants. Sequence analysis of their V1 and the V2 regions indicated that a 20 amino acid stretch of the V1 region had undergone recombination and was also associated with the emergence of isolates eliciting strong neutralization responses. These findings support the hypothesis that recombination of the V1 and V2 regions of the envelope play a role in neutralization escape of SIVcpz in chimpanzees infected naturally. Furthermore, the data confirm that the neutralizing antibody response plays an important role in the decline of plasma infectious virus titers in HIV-1 related SIVcpz nonpathogenic infection.

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Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype

Cited by 159 publications

References 13 publications

Relationship of HIV‐1 Envelope V2 and V3 Sequences of the Primary Isolates to the Viral Phenotype

Relationship of HIV‐1 Envelope V2 and V3 Sequences of the Primary Isolates to the Viral Phenotype

Convergent evolution within the V3 loop domain of human immunodeficiency virus type 1 in association with disease progression

Genetic variability of the V1 and V2 env domains of SIVcpz‐ant and neutralization pattern of plasma viruses in a chimpanzee infected naturally

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