Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins Associated with either Early or Chronic Infections

PLoS Pathogens

Charles B. Hicks¹  Beatrice H. Hahn²  William R. Schief³  Craig A. Magaret³  Hui Li⁴  Michael S. Saag⁵  Mohammed Asmal⁵  Joseph J. Eron⁵  Paul A. Goepfert⁵  Martin Markowitz⁵  Barton F. Haynes⁶  George M. Shaw⁶  Alan S. Lapedes⁷  Shuyi Wang⁷  Georgia D. Tomaras⁷  William A. Blattner⁷  Chunlai Jiang⁷  Feng Gao⁷  Ronald Swanstrom⁷  Yih-En Andrew Ban⁸  Li-Hua Ping⁹  Norman L. Letvin⁹  Allan C. DeCamp⁹  Myron S. Cohen⁹  Peter B. Gilbert^1,10  Jeffrey A. Anderson^1,11  Peter T. Hraber^1,12  Marcus Daniels^1,13  Tanmoy Bhattacharya^1,14  Mohan Krishnamoorthy^1,14  S. Gnanakaran^1,14  Jesus F. Salazar-Gonzalez^1,14  Julie M. Decker^1,14  Bette Korber^1,14  Tongye Shen^1,14  Brandon F. Keele^1,14  Brian Gaschen^1,14  Joseph G. Sodroski^1,15  Ming Zhang^1,15  Kelly A. Soderberg^1,15 

[1] Aaron Diamond AIDS Research Center, an affiliate of the Rockefeller University, New York, New York, United States of America;Arzeda Corporation, Seattle, Washington, United States of America;Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America;Center for Molecular Biophysics and Department of Biochemistry, Cellular & Molecular Biology, University of Tennessee, Knoxville, Tennessee, United States of America;Department of Biochemistry and Biophysics and the Division of Infectious Diseases Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Department of Biochemistry, University of Washington, Seattle, Washington, United States of America;Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Division of Viral Pathogenesis, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America;Duke University Medical Center, the Departments of Medicine and Surgery, and the Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America;Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, Maryland, United States of America;National Engineering Laboratory of AIDS Vaccine School of Life Science, Jilin University, Changchun, China;SAIC-Frederick, National Cancer Institute, Frederick, Maryland, United States of America;Santa Fe Institute, Santa Fe, New Mexico, United States of America;Theoretical Biology, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America;Vaccine Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United State of America

关键词: Sequence alignment;    Sequence motif analysis;    Multiple alignment calculation;    Antibodies;    Glycosylation;    Protein sequencing;    Phylogenetic analysis;    Sequence analysis;   

DOI  :  10.1371/journal.ppat.1002209

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413–415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.

【 授权许可】

CC BY