A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies

ABSTRACT Antibody PG9 is a prototypical member of a class of V1/V2-directed antibodies that effectively neutralizes diverse strains of HIV-1. We analyzed strain-specific resistance to PG9 using sequence and structural information. For multiply resistant strains, mutations in a short segment of V1/V2 resulted in gain of sensitivity to PG9 and related V1/V2 neutralizing antibodies, suggesting both a common mechanism of HIV-1 resistance to and a common mode of recognition by this class of antibodies.

[1]  Young Do Kwon,et al.  Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9 , 2011, Nature.

[2]  Pham Phung,et al.  Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target , 2009, Science.

[3]  J. Mascola,et al.  Crystal Structure of PG16 and Chimeric Dissection with Somatically Related PG9: Structure-Function Analysis of Two Quaternary-Specific Antibodies That Effectively Neutralize HIV-1 , 2010, Journal of Virology.

[4]  J. Mascola,et al.  Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies , 2011, Journal of Virology.

[5]  Feng Gao,et al.  Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa , 2006, Journal of Virology.

[6]  Michael S. Seaman,et al.  HIV-1 Neutralization Coverage Is Improved by Combining Monoclonal Antibodies That Target Independent Epitopes , 2012, Journal of Virology.

[7]  T. Kepler,et al.  Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors , 2011, Journal of Virology.

[8]  Pham Phung,et al.  Broad neutralization coverage of HIV by multiple highly potent antibodies , 2011, Nature.

[9]  A. Moreau,et al.  Naturally occurring substitutions of conserved residues in human immunodeficiency virus type 1 variants of different clades are involved in PG9 and PG16 resistance to neutralization. , 2012, The Journal of general virology.

[10]  Rajesh P. Ringe,et al.  Subtle alteration of residues including N-linked glycans in V2 loop modulate HIV-1 neutralization by PG9 and PG16 monoclonal antibodies. , 2012, Virology.

[11]  D. Burton,et al.  Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1 , 2010, Proceedings of the National Academy of Sciences.

[12]  Dennis R. Burton,et al.  Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16 , 2010, Journal of Virology.

[13]  L. Morris,et al.  Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 Loop , 2011, Journal of Virology.

[14]  J. Mascola,et al.  Mining the B cell repertoire for broadly neutralizing monoclonal antibodies to HIV-1. , 2009, Cell host & microbe.

[15]  J. Mascola,et al.  Efficient protein boosting after plasmid DNA or recombinant adenovirus immunization with HIV-1 vaccine constructs. , 2007, Vaccine.

[16]  Mario Roederer,et al.  Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 , 2010, Science.

[17]  Xiping Wei,et al.  Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies , 2005, Journal of Virology.