Variability of the conserved V3 loop tip motif in HIV-1 subtype B isolates collected from Brazilian and French patients

ABSTRACT Although human immunodeficiency virus type 1 (HIV-1) recombinants have been found with high frequency, little is known about the forces that select for these viruses or their importance to pathogenesis. Here we document the emergence and dynamics of 11 distinct HIV-1 recombinants in a man who was infected with two subtype B HIV-1 strains and progressed rapidly to AIDS without developing substantial cellular or humoral immune responses. Although numerous frequency oscillations were observed, a single recombinant lineage eventually came to dominate the population. Numerical simulations indicate that the successive recombinant forms displaced each other too rapidly to be explained by any simple model of random genetic drift or sampling variation. All of the recombinants, including several resulting from independent recombination events, possessed the same sequence motif in the V3 loop, suggesting intense selection on this segment of the viral envelope protein. The outgrowth of the predominant V3 loop recombinants was not, however, associated with changes in coreceptor utilization. The final variant was instead notable for having lost 3 of 14 potential glycosylation sites. We also observed high ratios of synonymous-to-nonsynonymous nucleotide changes—suggestive of purifying selection—in all viral populations, with particularly high ratios in newly arising recombinants. Our study, therefore, illustrates the unusual and important patterns of viral adaptation that can occur in a patient with weak immune responses. Although it is hard to tease apart cause and effect in a single patient, the correlation with disease progression in this patient suggests that recombination between divergent viruses, with its ability to create chimeras with increased fitness, can accelerate progression to AIDS.

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Effect on Serologic Reactivity of P-to-W Substitution in the Apex of the V3 Loop of the HIV-1 Subtype B Glycoprotein

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology ◽

10.1097/00042560-199801010-00014 ◽

1998 ◽

Vol 17 (1) ◽

pp. 91-92

Author(s):

Marleen Vanden Haesevelde ◽

Robert J. DeLeys ◽

Anja Van Geel ◽

Bart Vanderborght ◽

Morais de Sá ◽

...

Keyword(s):

V3 Loop ◽

Subtype B ◽

Hiv 1

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Polymorphism of the pedictive antigenic sites on the V3 loop of Brazilian HIV-1 subtype B strains

Memórias do Instituto Oswaldo Cruz ◽

10.1590/s0074-02761996000300015 ◽

1996 ◽

Vol 91 (3) ◽

pp. 339-342 ◽

Cited By ~ 5

Author(s):

MG Morgado ◽

ML Guimarães ◽

CBG Gripp ◽

I Neves Jr ◽

CI Costa ◽

...

Keyword(s):

V3 Loop ◽

Subtype B ◽

Antigenic Sites ◽

Hiv 1

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Position 22 of the V3 Loop is Associated with Co-Receptor Usage and Disease Progression in HIV-1 Subtype B Isolates

Current HIV Research ◽

10.2174/157016211798998727 ◽

2011 ◽

Vol 9 (8) ◽

pp. 636-641 ◽

Cited By ~ 1

Author(s):

Hai-Zhou Zhou ◽

Hua-Feng Xu ◽

Xiao-Min Xin ◽

Xiu-Ru Guan ◽

Jin Zhou

Keyword(s):

Disease Progression ◽

V3 Loop ◽

Receptor Usage ◽

Subtype B ◽

Hiv 1

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Application of Dried Blood Spot Specimens for Serologic Subtyping of Human Immunodeficiency Virus Type 1 in Thailand

Journal of Clinical Microbiology ◽

10.1128/jcm.37.3.804-806.1999 ◽

1999 ◽

Vol 37 (3) ◽

pp. 804-806 ◽

Cited By ~ 7

Author(s):

P. Chanbancherd ◽

A. E. Brown ◽

R. Trichavaroj ◽

P. Tienamporn ◽

P. Puthakird ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Dried Blood Spot ◽

V3 Loop ◽

Subtype B ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Blood Spot

Dried blood spot (DBS) specimens were assessed as an alternative to plasma for human immunodeficiency virus type 1 (HIV-1) serotyping by V3 loop peptide enzyme immunoassay. Nested PCR capable of distinguishing HIV-1 subtypes B and E was used as the reference standard. Ninety-two percent of DBS samples were typeable as either HIV-1 subtype B or E. Serotype results with DBS and plasma were identical for 254 of 257 specimens. A simple DBS collection method provides a convenient alternative for conducting HIV-1 serotype surveillance while retaining sensitivity and specificity.

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Resistance of Subtype C HIV-1 Strains to Anti-V3 Loop Antibodies

Advances in Virology ◽

10.1155/2012/803535 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

David Almond ◽

Chavdar Krachmarov ◽

James Swetnam ◽

Susan Zolla-Pazner ◽

Timothy Cardozo

Keyword(s):

Consensus Sequence ◽

3D Structure ◽

Structural Difference ◽

V3 Loop ◽

Subtype C ◽

Subtype B ◽

Structural Rigidity ◽

Global Spread ◽

Secondary Protein Structure ◽

Hiv 1

HIV-1’s subtype C V3 loop consensus sequence exhibits increased resistance to anti-V3 antibody-mediated neutralization as compared to the subtype B consensus sequence. The dynamic 3D structure of the consensus C V3 loop crown, visualized byab initiofolding, suggested that the resistance derives from structural rigidity and non-β-strand secondary protein structure in the N-terminal strand of theβ-hairpin of the V3 loop crown, which is where most known anti-V3 loop antibodies bind. The observation of either rigidity or non-β-strand structure in this region correlated with observed resistance to antibody-mediated neutralization in a series of chimeric pseudovirus (psV) mutants. The results suggest the presence of an epitope-independent, neutralization-relevant structural difference in the antibody-targeted region of the V3 loop crown between subtype C and subtype B, a difference that we hypothesize may contribute to the divergent pattern of global spread between these subtypes. As antibodies to a variable loop were recently identified as an inverse correlate of risk for HIV infection, the structure-function relationships discussed in this study may have relevance to HIV vaccine research.

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Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc

Antiviral Chemistry and Chemotherapy ◽

10.1177/20402066211025156 ◽

2021 ◽

Vol 29 ◽

pp. 204020662110251

Author(s):

ME Lewis ◽

B Jubb ◽

P Simpson ◽

A Lopatukhin ◽

D Kireev ◽

...

Keyword(s):

Amino Acid ◽

Virologic Failure ◽

Natural Resistance ◽

V3 Loop ◽

Amino Acid Residues ◽

Subtype B ◽

Loop Sequence ◽

Hiv 1 ◽

Amino Acid Variants

Introduction Maraviroc inhibits CCR5-tropic HIV-1 across different subtypes in vitro and has demonstrated efficacy in clinical trials. V3-loop amino acid variants observed in individual maraviroc-resistant viruses have not been found to be predictive of reduced susceptibility. Sequence-database searches have demonstrated that approximately 7.3% of viruses naturally encode these variants, raising concerns regarding potential pre-existing resistance. A study from Russia reported that combinations of these same amino acids are present in the V3 loops of the Russian variant subtype A (IDU-A, now A6) with a much greater prevalence (range: 74.4%–92.3%) depending on the combination. However, these studies and database searches did not include phenotypic evaluation. Methods Sixteen Russian HIV-1 isolates (including sub-subtype A6 viruses) were assessed for V3 loop sequence and phenotypic susceptibility to maraviroc. Results All 12 of the A6 viruses and 2/4 subtype B isolates encoded V3-loop variants that have previously been identified in individual virus isolates with reduced susceptibility to maraviroc. However, despite the prevalence of these V3-loop amino acid variants among the tested viruses, phenotypic sensitivity to maraviroc was observed in all instances. Similarly, reduced susceptibility to maraviroc was not found in virus from participants who experienced virologic failure in a clinical study of maraviroc in Russia (A4001101, [NCT01275625]). Discussion Altogether, these data confirm that the presence of individual or combinations of V3-loop amino acid residues in sub-subtype A6 viruses alone does not predict natural resistance to maraviroc and that V3-loop genotype analysis of R5 virus prior to treatment is not helpful in predicting clinical outcome.

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A7 Co-receptor tropism determined by genotypic assay in HIV-1 non-B subtypes circulating in Cuba: Implications for pathogenesis and Maraviroc resistance

Virus Evolution ◽

10.1093/ve/vez002.006 ◽

2019 ◽

Vol 5 (Supplement_1) ◽

Author(s):

M Méndez ◽

V Kourí ◽

L Pérez ◽

Y Alemán ◽

Y Martínez ◽

...

Keyword(s):

Viral Load ◽

Chemokine Receptors ◽

Phylogenetic Analyses ◽

Amino Acid Sequences ◽

High Rate ◽

V3 Loop ◽

Older Individuals ◽

Subtype B ◽

Genotypic Assay ◽

Hiv 1

Abstract The V3 loop of the HIV-1 envelope (env) gene is involved in binding to the chemokine receptors CCR5 and CXCR4, thus determining viral tropism. With the aim of genetically characterizing the C2V3 env region of HIV-1 samples from Cuban patients, naive to Maraviroc (MVC) therapy, 115 plasma samples were taken in the period of 2014–6 and analyzed by sequencing of the C2V3 region. HIV-1 subtyping was performed using COMET V.2 and Rega subtyping toolV.3 software. Subtypes were confirmed by phylogenetic analyses using Mega-6. Prediction of co-receptor tropism was performed using the geno2pheno algorithm. The viral mutations associated to MVC resistance were analyzed, as well as the association of the subtype with clinical, epidemiological, virological, and immunological variables. The subtypes detected using the C2V3 region were CRF20, 23, 24_BG (35 patients, 30.4%); Subtype B (33 patients, 28.7%); CRF19_cpx (30 patients, 26.1%); CRF18_cpx (10 patients, 8.7%); and others (7 patients, 6.1%). Overall, 60 per cent of the viruses exhibited R5 phenotype, 14.8 per cent were R5X4 and 25.2 per cent were X4. Interestingly, CRF19_cpx virus was associated with having phenotype X4 [46.7%, P = 0.0047, odds ratio (OR): 3.96, 95% confidence interval (95% CI): 1.59–9.84], with infection in young individuals (39.1%, P = 0.025, OR: 3,548; 95% CI: 1,136–11,077) and with higher values of viral load (P ≤ 0.05). The comparison of the amino acid sequences of the V3 loop showed differences between the B and non-B subtypes (P = 0.0001). Mutations reported to be associated with MVC resistance, were detected in 75.7 per cent of the samples, in positions 11 (6.1%), 13 (49.6%), 25 (6.1%), 316 (7.0%), 323 (11.3%), and 319 (3.5%) of Gp120, particularly in the recombinant forms CRF19_cpx and CRF_BGs. HIV variants that use the CXCR4 co-receptor were associated with more than 10 years of diagnosis, with older individuals, in the AIDS stage, with low CD4 counts and higher viral load levels (P < 0.05). The results support the hypothesis previously stated that CRF19_cpx viruses could be more pathogenic and would have limitations for the use of MVC. The high rate of mutations associated to MVC among non-B Cuban subtypes should be further studied.

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Coreceptor Tropism in Human Immunodeficiency Virus Type 1 Subtype D: High Prevalence of CXCR4 Tropism and Heterogeneous Composition of Viral Populations

Journal of Virology ◽

10.1128/jvi.00218-07 ◽

2007 ◽

Vol 81 (15) ◽

pp. 7885-7893 ◽

Cited By ~ 117

Author(s):

Wei Huang ◽

Susan H. Eshleman ◽

Jonathan Toma ◽

Signe Fransen ◽

Eric Stawiski ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

V3 Loop ◽

Coreceptor Tropism ◽

Subtype B ◽

Immunodeficiency Virus ◽

Cxcr4 Coreceptor ◽

Subtype A ◽

Hiv 1

ABSTRACT In human immunodeficiency virus type 1 (HIV-1) subtype B, CXCR4 coreceptor use ranges from ∼20% in early infection to ∼50% in advanced disease. Coreceptor use by non-subtype B HIV is less well characterized. We studied coreceptor tropism of subtype A and D HIV-1 collected from 68 pregnant, antiretroviral drug-naive Ugandan women (HIVNET 012 trial). None of 33 subtype A or 10 A/D-recombinant viruses used the CXCR4 coreceptor. In contrast, nine (36%) of 25 subtype D viruses used both CXCR4 and CCR5 coreceptors. Clonal analyses of the nine subtype D samples with dual or mixed tropism revealed heterogeneous viral populations comprised of X4-, R5-, and dual-tropic HIV-1 variants. In five of the six samples with dual-tropic strains, V3 loop sequences of dual-tropic clones were identical to those of cocirculating R5-tropic clones, indicating the presence of CXCR4 tropism determinants outside of the V3 loop. These dual-tropic variants with R5-tropic-like V3 loops, which we designated “dual-R,” use CCR5 much more efficiently than CXCR4, in contrast to dual-tropic clones with X4-tropic-like V3 loops (“dual-X”). These observations have implications for pathogenesis and treatment of subtype D-infected individuals, for the association between V3 sequence and coreceptor tropism phenotype, and for understanding potential mechanisms of evolution from exclusive CCR5 use to efficient CXCR4 use by subtype D HIV-1.

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