Relation of Phenotype Evolution of HIV-1 to Envelope V2 Configuration

Groenink, M.; Fouchier, Ron A. M.; Broersen, S.; Baker, Carleton H.; Koot, M.; Wout, Angélique B. van‘t; Huisman, H. G.; Miedema, Frank; Tersmette, M.; Schuitemaker, Hanneke

doi:10.1126/science.8502996

Cited by 212 publications

(172 citation statements)

References 20 publications

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…Although CCR-5 vs. CXCR-4 tropism is regulated largely by the envelope V3 loop, there has been a number of reports documenting the ability of the V1͞V2 region to modulate HIV-1 cell tropism and replication potential (30)(31)(32)(33), although others have suggested only a minor role for the V1͞V2 domain (34). Our data documenting a major role for V1͞V2 in regulating the interaction with CCR-3 support these previous findings and suggest that V1͞V2 is indeed likely to play a significant role in modulating the envelope:coreceptor interaction.…”

Section: Discussionmentioning

confidence: 99%

The ability of HIV type 1 to use CCR-3 as a coreceptor is controlled by envelope V1/V2 sequences acting in conjunction with a CCR-5 tropic V3 loop

Ross

Cullen

1998

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Although infection by primary HIV type 1 (HIV-1) isolates normally requires the functional interaction of the viral envelope protein with both CD4 and the CCR-5 coreceptor, a subset of such isolates also are able to use the distinct CCR-3 receptor. By analyzing the ability of a series of wild-type and chimeric HIV-1 envelope proteins to mediate CCR-3-dependent infection, we have determined that CCR-3 tropism maps to the V1 and V2 variable region of envelope. Although substitution of the V1͞V2 region of a CCR-3 tropic envelope into the context of a CCR-5 tropic envelope is both necessary and sufficient to confer CCR-3 tropism, this same substitution has no phenotypic effect when inserted into a CXCR-4 tropic HIV-1 envelope context. However, this latter chimera acquires both CCR-3 and CCR-5 tropism when a CCR-5 tropic V3 loop sequence also is introduced. These data demonstrate that the V1͞2 region of envelope can, like the V3 loop region, encode a particular coreceptor requirement and suggest that a functional envelope:CCR-3 interaction may depend on the cooperative interaction of CCR-3 with both the V1͞V2 and the V3 region of envelope.

show abstract

Section: Discussionmentioning

confidence: 99%

The ability of HIV type 1 to use CCR-3 as a coreceptor is controlled by envelope V1/V2 sequences acting in conjunction with a CCR-5 tropic V3 loop

Ross

Cullen

1998

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…5). Before virus isolates obtained positively charged amino acid residues in V3 that are typical for SI isolates, amino acid substitutions and insertions occurred in V2, resulting in elongated, more positively charged V2 domains with frequent addition or relocation of potential N-linked glycosylation sites [93]. More detailed analysis revealed that this V2 polymorphism may occur in only a minor fraction of the HIV-1 isolates present in an infected individual [99].…”

Section: Phenotype Evolution Of Hiv-1mentioning

confidence: 99%

“…4). In about 70% of primary SI but in only 35% of NSI HIV-1 isolates, the V2 domain is elongated and contains positively charged amino acid residues and extra or dislocated potential N-linked glycosylation sites [93,99]. Although statistical analysis and construction of chimeric proviruses suggested that these characteristics of V2 contribute to SI capacity, site-directed mutagenesis is required to formally prove this.…”

Section: Si Capacitymentioning

confidence: 99%

“…Construction of HIV-1 proviruses and vaccinia vectors expressing chimeric envelope proteins have clearly defined the V2 and V3 domains as important determinants of SI capacity of HIV-1 [65,66,68,70,71,93,94]. The almost perfect correlation between SI capacity of HIV-1 isolates with positively charged amino acid residues at positions 306 and 320 in V3 indicate that V3 is the major determinant of SI phenotype [95,96].…”

Section: Si Capacitymentioning

confidence: 99%

“…These observations may at least in part explain the increased virus load in late asymptomatic HIV infection in individuals, regardless of SI capacity of the variants present in the infected individuals [13,140,141]. Since V3 together with other variable domains determine both SI capacity and tropism of HIV-1, evolution from NSI macrophage-tropic towards SI and/or T-cell-tropic isolates may result from consecutive changes in these variable domains [65,66,68,70,71,[92][93][94]100,104]. Knowledge of the exact sequence of amino acid substitutions would enable prediction of phenotype evolution, and may thus be useful as a prognostic marker for disease progression and for prescription of antiviral therapy.…”

Section: Phenotype Evolution Of Hiv-1mentioning

confidence: 99%

See 2 more Smart Citations

Molecular determinants of human immunodeficiency virus type I phenotype variability

Fouchier

Schuitemaker

1996

Eur J Clin Investigation

View full text Add to dashboard Cite

Abstract.The clinical course of HIV-1-infected individuals can be highly variable. Progression to AIDS can occur within 1 year after infection but symptom-free infection for more than 15 years has also been reported. This variation can either be determined by host factors, the biological variability of the virus or both. Here the molecular determinants and clinical relevance of HIV-1 biological phenotype variability are reviewed.

show abstract

Genetically and epidemiologically related ?non-syncytium-inducing? isolates of HIV-1 display heterogeneous growth patterns in macrophages

et al. 2000

View full text Add to dashboard Cite

The objective of this study was to identify phenotypic parameters that could distinguish among seemingly homogeneous non-syncytium-inducing (NSI) viruses and that might provide a surrogate marker for clinical progression in pediatric human immunodeficiency virus type 1 (HIV-1) infection. We undertook a pilot analysis of 15 independent HIV-1 isolates collected prospectively from two mothers and their four children who displayed a spectrum of disease stages ranging from CDC categories A1 to C3. Viruses were evaluated for their ability to replicate in primary cells (including monocyte-derived macrophages [MDM]) and cell lines, for their co-receptor preference and for genetic features of the V3 hypervariable domain of env. Virtually all isolates displayed NSI phenotypes that were restricted in their capacity to replicate in cell lines and displayed V3 loops with uniformly low net positive charges. NSI viruses from two symptomatic children and one mother were macrophage-tropic, whereas NSI isolates from two asymptomatic children were unable to replicate in MDM and were designated primary lymphotropic viruses. Only one isolate was syncytium-inducing (SI), replicated in a variety of cell lines and in MDM, used multiple co-receptors, and was dual tropic, rather than a mixture of T-cell tropic and M-tropic viruses, as assessed by genetic analysis. Phenotypic heterogeneity among NSI viruses is revealed in the ability of isolates to replicate in MDM. This characteristic is related to disease stage and provides a potentially new in vitro criterion to distinguish among NSI isolates that is unlinked to other surrogate markers.

show abstract

Relation of Phenotype Evolution of HIV-1 to Envelope V2 Configuration

Cited by 212 publications

References 20 publications

The ability of HIV type 1 to use CCR-3 as a coreceptor is controlled by envelope V1/V2 sequences acting in conjunction with a CCR-5 tropic V3 loop

The ability of HIV type 1 to use CCR-3 as a coreceptor is controlled by envelope V1/V2 sequences acting in conjunction with a CCR-5 tropic V3 loop

Molecular determinants of human immunodeficiency virus type I phenotype variability

Genetically and epidemiologically related ?non-syncytium-inducing? isolates of HIV-1 display heterogeneous growth patterns in macrophages

Contact Info

Product

Resources

About