HIV-1 envelope sequence-based diversity measures for identifying recent infections

To investigate why human immunodeficiency virus type 2 (HIV-2) is less virulent than HIV-1, the evolution of coreceptor usage, autologous neutralization, envelope sequence and glycosylation was studied in sequentially obtained virus isolates and sera from four HIV-2-infected individuals. Neutralization of primary HIV-2 isolates was tested by a cell line-based assay and IgG purified from patients' sera. Significant autologous neutralization was observed for the majority (39 of 54) of the HIV-2 serum–virus combinations tested, indicating that neutralization escape is rare in HIV-2 infection. Furthermore, sera from 18 HIV-2 patients displayed extensive heterologous cross-neutralization when tested against a panel of six primary HIV-2 isolates. This indicates that HIV-2 is intrinsically more sensitive to antibody neutralization than HIV-1. In line with earlier reports, HIV-2 isolates could use several alternative receptors in addition to the major coreceptors CCR5 and CXCR4. Intrapatient evolution from CCR5 use to CXCR4 use was documented for the first time. Furthermore, CXCR4 use was linked to the immunological status of the patients. Thus, all CXCR4-using isolates, except one, were obtained from patients with CD4 counts below 200 cells μl−1. Sequence analysis revealed an association between coreceptor usage and charge of the V3 loop of the HIV-2 envelope, as well as an association between the rate of disease progression and the glycosylation pattern of the envelope protein. Furthermore, HIV-2 isolates had fewer glycosylation sites in the V3 domain than HIV-1 (two to three versus four to five). It is proposed here that HIV-2 has a more open and accessible V3 domain than HIV-1, due to differences in glycan packing, and that this may explain its broader coreceptor usage and greater sensitivity to neutralizing antibodies.

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From predicting to analyzing HIV-1 resistance to broadly neutralizing antibodies

10.7287/peerj.preprints.1304v1 ◽

2015 ◽

Author(s):

Anna Feldmann ◽

Nico Pfeifer

Keyword(s):

Neutralizing Antibodies ◽

Computational Models ◽

Prediction Models ◽

Scale Up ◽

Test Sequence ◽

Broadly Neutralizing Antibodies ◽

Subtype B ◽

Envelope Sequence ◽

Experimental Findings ◽

Hiv 1

Treatment with broadly neutralizing antibodies (bNAbs) has recently proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. For optimal treatment, susceptibility of the patient's viral strains to a particular bNAb has to be ensured. Since no computational approaches are so far available, susceptibility can only be tested in expensive and time-consuming neutralization experiments. Here, we present well-performing computational models (AUC up to 0.84) that can predict HIV-1 resistance to bNAbs given the envelope sequence of the virus. Having learnt important binding sites of the bNAbs from the envelope sequence, the models are also biologically meaningful and useful for epitope recognition. Additional to the prediction result, we provide a motif logo that displays the contribution of the pivotal residues of the test sequence to the prediction. As our prediction models are based on non-linear kernels, we introduce a new visualization technique to improve the model interpretability. Moreover, we confirmed previous experimental findings that there is a trend towards antibody resistance for the subtype B population of the virus. While previous experiments considered rather small and selected cohorts, we were able to show a similar trend for the global HIV-1 population comprising all major subtypes by predicting the neutralization sensitivity for around 36,000 HIV-1 sequences - a scale-up which is very difficult to achieve in an experimental setting.

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P17-09. Immunization with a single HIV-1 envelope sequence can generate CD8+ T lymphocytes capable of recognizing multiple variant forms of envelope

Retrovirology ◽

10.1186/1742-4690-6-s3-p291 ◽

2009 ◽

Vol 6 (S3) ◽

Author(s):

SL Hulot ◽

MS Seaman ◽

LA Dorosh ◽

BT Korber ◽

NL Letvin

Keyword(s):

T Lymphocytes ◽

Cd8 T Lymphocytes ◽

Envelope Sequence ◽

Hiv 1

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Isolation and Envelope Sequence of a Highly Divergent HIV-1 Isolate: Definition of a New HIV-1 Group

Virology ◽

10.1006/viro.1994.1640 ◽

1994 ◽

Vol 205 (1) ◽

pp. 247-253 ◽

Cited By ~ 104

Author(s):

Pierre Charneau ◽

Andrew M. Borman ◽

Caroline Quillent ◽

Denise Guétard ◽

Sophie Chamaret ◽

...

Keyword(s):

Envelope Sequence ◽

Definition Of ◽

Hiv 1

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From predicting to analyzing HIV-1 resistance to broadly neutralizing antibodies

10.7287/peerj.preprints.1304 ◽

2015 ◽

Author(s):

Anna Feldmann ◽

Nico Pfeifer

Keyword(s):

Neutralizing Antibodies ◽

Computational Models ◽

Prediction Models ◽

Scale Up ◽

Test Sequence ◽

Broadly Neutralizing Antibodies ◽

Subtype B ◽

Envelope Sequence ◽

Experimental Findings ◽

Hiv 1

Treatment with broadly neutralizing antibodies (bNAbs) has recently proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. For optimal treatment, susceptibility of the patient's viral strains to a particular bNAb has to be ensured. Since no computational approaches are so far available, susceptibility can only be tested in expensive and time-consuming neutralization experiments. Here, we present well-performing computational models (AUC up to 0.84) that can predict HIV-1 resistance to bNAbs given the envelope sequence of the virus. Having learnt important binding sites of the bNAbs from the envelope sequence, the models are also biologically meaningful and useful for epitope recognition. Additional to the prediction result, we provide a motif logo that displays the contribution of the pivotal residues of the test sequence to the prediction. As our prediction models are based on non-linear kernels, we introduce a new visualization technique to improve the model interpretability. Moreover, we confirmed previous experimental findings that there is a trend towards antibody resistance for the subtype B population of the virus. While previous experiments considered rather small and selected cohorts, we were able to show a similar trend for the global HIV-1 population comprising all major subtypes by predicting the neutralization sensitivity for around 36,000 HIV-1 sequences - a scale-up which is very difficult to achieve in an experimental setting.

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THETA: a new genotypic approach for predicting HIV-1 CRF02-AG coreceptor usage

Bioinformatics ◽

10.1093/bioinformatics/btz585 ◽

2019 ◽

Author(s):

Chloé Dimeglio ◽

Stéphanie Raymond ◽

Nicolas Jeanne ◽

Christelle Reynes ◽

Romain Carcenac ◽

...

Keyword(s):

Sequence Data ◽

Operator Method ◽

Hiv Therapy ◽

Gp41 Ectodomain ◽

Envelope Sequence ◽

Selection Operator ◽

Hiv Envelope ◽

The Impact ◽

Hiv 1

Abstract Motivation The circulating recombinant form of HIV-1 CRF02-AG is the most frequent non-B subtype in Europe. Anti-HIV therapy and pathophysiological studies on the impact of HIV-1 tropism require genotypic determination of HIV-1 tropism for non-B subtypes. But genotypic approaches based on analysis of the V3 envelope region perform poorly when used to determine the tropism of CRF02-AG. We, therefore, designed an algorithm based on information from the gp120 and gp41 ectodomain that better predicts the tropism of HIV-1 subtype CRF02-AG. Results We used a bio-statistical method to identify the genotypic determinants of CRF02-AG coreceptor use. Toulouse HIV Extended Tropism Algorithm (THETA), based on a Least Absolute Shrinkage and Selection Operator method, uses HIV envelope sequence from phenotypically characterized clones. Prediction of R5X4/X4 viruses was 86% sensitive and that of R5 viruses was 89% specific with our model. The overall accuracy of THETA was 88%, making it sufficiently reliable for predicting the tropism of subtype CRF02-AG sequences. Availability and implementation Binaries are freely available for download at https://github.com/viro-tls/THETA. It was implemented in Matlab and supported on MS Windows platform. The sequence data used in this work are available from GenBank under the accession numbers MK618182-MK618417.

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A Short-Term Assessment of Nascent HIV-1 Transmission Clusters Among Newly Diagnosed Individuals Using Envelope Sequence-Based Phylogenetic Analyses

AIDS Research and Human Retroviruses ◽

10.1089/aid.2019.0142 ◽

2019 ◽

Vol 35 (10) ◽

pp. 906-919

Author(s):

Alexis Kafando ◽

Bouchra Serhir ◽

Florence Doualla-Bell ◽

Eric Fournier ◽

Mohamed Ndongo Sangaré ◽

...

Keyword(s):

Phylogenetic Analyses ◽

Newly Diagnosed ◽

Short Term ◽

Envelope Sequence ◽

Hiv 1

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Structure–function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design

Nature Reviews Immunology ◽

10.1038/nri2801 ◽

2010 ◽

Vol 10 (7) ◽

pp. 527-535 ◽

Cited By ~ 107

Author(s):

Susan Zolla-Pazner ◽

Timothy Cardozo

Keyword(s):

Structure Function ◽

Vaccine Design ◽

Variable Regions ◽

Envelope Sequence ◽

Hiv 1

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Coreceptor Switch in R5-Tropic Simian/Human Immunodeficiency Virus-Infected Macaques

Journal of Virology ◽

10.1128/jvi.00759-07 ◽

2007 ◽

Vol 81 (16) ◽

pp. 8621-8633 ◽

Cited By ~ 44

Author(s):

Siu-hong Ho ◽

Silvana Tasca ◽

Lili Shek ◽

Amy Li ◽

Agegnehu Gettie ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Recognition ◽

Primate Model ◽

Subtype B ◽

Immunodeficiency Virus ◽

Envelope Sequence ◽

Coreceptor Switch ◽

Virus Specific Antibody ◽

Cellular Immune ◽

Hiv 1

ABSTRACT The basis for the switch from CCR5 to CXCR4 coreceptor usage seen in ∼50% of human immunodeficiency virus type 1 (HIV-1) subtype B-infected individuals as disease advances is not well understood. Among the reasons proposed are target cell limitation and better immune recognition of the CXCR4 (X4)-tropic compared to the CCR5 (R5)-tropic virus. We document here X4 virus emergence in a rhesus macaque (RM) infected with R5-tropic simian/human immunodeficiency virus, demonstrating that coreceptor switch can happen in a nonhuman primate model of HIV/AIDS. The switch to CXCR4 usage in RM requires envelope sequence changes in the V3 loop that are similar to those found in humans, suggesting that the R5-to-X4 evolution pathways in the two hosts overlap. Interestingly, compared to the inoculating R5 virus, the emerging CXCR4-using virus is highly neutralization sensitive. This finding, coupled with the observation of X4 evolution and appearance in an animal with undetectable circulating virus-specific antibody and low cellular immune responses, lends further support to an inhibitory role of antiviral immunity in HIV-1 coreceptor switch.

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