HIV-1 Intrapatient Sequence Diversity in the Immunogenic V3 Region

Korber, Bette; Wolinsky, Steven M.; Haynes, Barton F.; Kunstman, Kevin; Levy, Robert M.; Furtado, Manohar R.; Otto, Patricia; Myers, Gerald

doi:10.1089/aid.1992.8.1461

Cited by 30 publications

(18 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic sequence analysis focused on the viral env region around the third hypervariable (V3) domain. This region was analyzed because it is an important site of host-virus interaction and is known to tolerate frequent mutations (37)(38)(39)(40)(41)(42)(43)(44)(45). Between 6 and 21 env sequences were amplified by PCR from each individual visit, yielding a total of 873 clones that were sequenced and analyzed.…”

Section: Resultsmentioning

confidence: 99%

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline

Markham

Wang

Weisstein

et al. 1998

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

103

View full text Add to dashboard Cite

Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.

show abstract

Section: Resultsmentioning

confidence: 99%

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline

Markham

Wang

Weisstein

et al. 1998

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

103

View full text Add to dashboard Cite

show abstract

“…The mean interpatient sequence diversity of the V3 domain was found to be narrower in BAL (351 comparisons) than in PBMC (276 comparisons) (11.0% + 6.4% vs. 14.5% ± 8.2%, P < 0.0001). To examine whether these differences were present throughout the V3 domain, or were limited to a particular region, interpatient comparisons were repeated for sequences spanning the regions at either the N-terminal or C-terminal sides of nucleotides encoding the conserved crown ofthe V3 loop (26). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Examination ofthe V3 loop amino acid sequences from BAL supported this conclusion, with a conserved motif at the C-terminal end being enriched at this site. A conserved V3 motif has also been reported in strains from brain tissues compared to those in blood (26), raising the possibility that viral tropism for diverse tissues is dependent on distinct V3 loop structures. In contrast, the wide interpatient nucleotide and amino acid divergence at the N-terminal end of the V3 domain suggests that this region could be evolving under immunological selection pressures that differ from individual to individual and depend on HLA type and T-cell receptor repertoire (22).…”

mentioning

confidence: 99%

Human immunodeficiency virus type 1 strains in the lungs of infected individuals evolve independently from those in peripheral blood and are highly conserved in the C-terminal region of the envelope V3 loop.

Itescu

Simonelli

Winchester

et al. 1994

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

View full text Add to dashboard Cite

show abstract

“…The V3 loop plays a central role in the life cycle of HIV-1 but, like other regions of the genome, displays subtype-specific sequence variation (42,44,51). We are interested in the possibility that these sequence differences can impact virus biology in a subtype-specific way.…”

Section: Discussionmentioning

confidence: 99%

Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins

Patel

Hoffman

Swanstrom

2008

J Virol

View full text Add to dashboard Cite

The V3 region of the human immunodeficiency virus type 1 gp120 Env protein is a key domain in Env due to its role in interacting with the coreceptors CCR5 and CXCR4. We examined potential subtype-specific V3 region differences by comparing patterns of amino acid variability and probing for subtype-specific structures using 11 anti-V3 monoclonal antibodies (V3 MAbs). Differences between the subtypes in patterns of variability were most evident in the stem and turn regions of V3 (positions 9 to 24), with the two subtypes being very similar in the base region. The characteristics of the binding of V3 MAbs to Env proteins of the subtype B virus JR-FL and the subtype C virus BR025 suggested three patterns, as each group of MAbs recognized a specific conformation-or sequence-based epitope. Viruses pseudotyped with Env from JR-FL and BR025 were resistant to neutralization by the V3 MAbs, although the replacement of the Env V3 region of the SF162 virus with the JR-FL V3 created a pseudotyped virus that was hypersensitive to neutralization. A single mutation in V3 (H13R) made this chimeric Env selectively resistant to one group of V3 MAbs, consistent with the mAb binding properties. We hypothesize that there are intrinsic differences in V3 conformation between subtype B and subtype C that are localized to the stem and turn regions and that these differences have two important biological consequences: first, subtype B and subtype C V3 regions can have subtype-specific epitopes that will inherently limit antibody cross-reactivity, and second, V3 conformational differences may potentiate the frequent evolution of R5-into X4-tropic variants of subtype B but limit subtype C virus from using the same mechanism to evolve X4-tropic variants as efficiently.The binding of the human immunodeficiency virus type 1 (HIV-1) to its target cell is mediated by the viral envelope glycoprotein Env. The glycoprotein is expressed as a gp160 precursor that is proteolytically cleaved into two mature subunits, the gp120 surface protein and the gp41 transmembrane protein. On the surface of the virus, Env is present as a trimer of the gp120 and gp41 heterodimers (2, 62). When the virus binds to its primary receptor, CD4, Env undergoes conformational changes, exposing previously hidden regions and creating new structural elements. Env then binds to a coreceptor, usually the chemokine receptor CCR5 or CXCR4 (23, 26, 80), which triggers further structural changes that promote fusion to the target cell (27, 35).The Env sequence can be viewed as being composed of regions that are relatively constant (C1 to C5) and regions that on a population basis are much more variable (V1 to V5) (70). As the only viral protein expressed on the surface of the virus, Env is the sole target of neutralizing antibodies that supply selective pressure to favor mutated variants capable of evading the immune response (47, 79). The V3 region is associated with coreceptor preference and physically contacts the chemokine receptor as part of the fusion process (23,26,80). Sequen...

show abstract

HIV-1 Intrapatient Sequence Diversity in the Immunogenic V3 Region

Cited by 30 publications

References 2 publications

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline

Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline

Human immunodeficiency virus type 1 strains in the lungs of infected individuals evolve independently from those in peripheral blood and are highly conserved in the C-terminal region of the envelope V3 loop.

Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins

Contact Info

Product

Resources

About