skip to main content
Show search Show menu
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

Abstract

The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [1];  [1];  [1];  [1];  [1] more »;  [3];  [4];  [5];  [6];  [7];  [7];  [8];  [9];  [9];  [10];  [11];  [11];  [12];  [1];  [1];  [13];  [13];  [1] « less
+ Show Author Affiliations
  1. Duke Univ. Medical Center, Durham, NC (United States)
  2. Univ. of Montreal, Quebec (Canada)
  3. Kamuzu Central Hospital, Lilongwe (Malawi). Univ. of North Carolina Project
  4. Univ. of North Carolina, Chapel Hill, NC (United States)
  5. Kilimanjaro Christian Medical Center, Moshi (Tanzania)
  6. London School of Hygiene and Tropical Medicine, London (United Kingdom)
  7. National Inst. for Communicable Diseases, Johannesburg (South Africa)
  8. Duke Univ. Medical Center, Durham, NC (United States); National Inst. for Communicable Diseases, Johannesburg (South Africa)
  9. New York Univ. School of Medicine, New York, NY (United States)
  10. National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center
  11. Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine
  12. Harvard Medical School, Boston, MA (United States). Dana-Farber Cancer Inst.
  13. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1233164
Report Number(s):
LA-UR-14-24938
Journal ID: ISSN 1931-3128; PII: S1931312815003340
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Cell Host & Microbe
Additional Journal Information:
Journal Volume: 18; Journal Issue: 3; Journal ID: ISSN 1931-3128
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Moody, M.  Anthony, Gao, Feng, Gurley, Thaddeus  C., Amos, Joshua  D., Kumar, Amit, Hora, Bhavna, Marshall, Dawn  J., Whitesides, John  F., Xia, Shi-Mao, Parks, Robert, Lloyd, Krissey  E., Hwang, Kwan-Ki, Lu, Xiaozhi, Bonsignori, Mattia, Finzi, Andrés, Vandergrift, Nathan  A., Alam, S.  Munir, Ferrari, Guido, Shen, Xiaoying, Tomaras, Georgia  D., Kamanga, Gift, Cohen, Myron  S., Sam, Noel  E., Kapiga, Saidi, Gray, Elin S., Tumba, Nancy  L., Morris, Lynn, Zolla-Pazner, Susan, Gorny, Miroslaw  K., Mascola, John  R., Hahn, Beatrice H., Shaw, George  M., Sodroski, Joseph  G., Liao, Hua-Xin, Montefiori, David C., Hraber, Peter T., Korber, Bette T., and Haynes, Barton F. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. United States: N. p., 2015. Web. doi:10.1016/j.chom.2015.08.006.
Copy to clipboard
Moody, M.  Anthony, Gao, Feng, Gurley, Thaddeus  C., Amos, Joshua  D., Kumar, Amit, Hora, Bhavna, Marshall, Dawn  J., Whitesides, John  F., Xia, Shi-Mao, Parks, Robert, Lloyd, Krissey  E., Hwang, Kwan-Ki, Lu, Xiaozhi, Bonsignori, Mattia, Finzi, Andrés, Vandergrift, Nathan  A., Alam, S.  Munir, Ferrari, Guido, Shen, Xiaoying, Tomaras, Georgia  D., Kamanga, Gift, Cohen, Myron  S., Sam, Noel  E., Kapiga, Saidi, Gray, Elin S., Tumba, Nancy  L., Morris, Lynn, Zolla-Pazner, Susan, Gorny, Miroslaw  K., Mascola, John  R., Hahn, Beatrice H., Shaw, George  M., Sodroski, Joseph  G., Liao, Hua-Xin, Montefiori, David C., Hraber, Peter T., Korber, Bette T., & Haynes, Barton F. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. United States. https://doi.org/10.1016/j.chom.2015.08.006
Copy to clipboard
Moody, M.  Anthony, Gao, Feng, Gurley, Thaddeus  C., Amos, Joshua  D., Kumar, Amit, Hora, Bhavna, Marshall, Dawn  J., Whitesides, John  F., Xia, Shi-Mao, Parks, Robert, Lloyd, Krissey  E., Hwang, Kwan-Ki, Lu, Xiaozhi, Bonsignori, Mattia, Finzi, Andrés, Vandergrift, Nathan  A., Alam, S.  Munir, Ferrari, Guido, Shen, Xiaoying, Tomaras, Georgia  D., Kamanga, Gift, Cohen, Myron  S., Sam, Noel  E., Kapiga, Saidi, Gray, Elin S., Tumba, Nancy  L., Morris, Lynn, Zolla-Pazner, Susan, Gorny, Miroslaw  K., Mascola, John  R., Hahn, Beatrice H., Shaw, George  M., Sodroski, Joseph  G., Liao, Hua-Xin, Montefiori, David C., Hraber, Peter T., Korber, Bette T., and Haynes, Barton F. 2015. "Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses". United States. https://doi.org/10.1016/j.chom.2015.08.006. https://www.osti.gov/servlets/purl/1233164.
Copy to clipboard
@article{osti_1233164,
title = {Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses},
author = {Moody, M.  Anthony and Gao, Feng and Gurley, Thaddeus  C. and Amos, Joshua  D. and Kumar, Amit and Hora, Bhavna and Marshall, Dawn  J. and Whitesides, John  F. and Xia, Shi-Mao and Parks, Robert and Lloyd, Krissey  E. and Hwang, Kwan-Ki and Lu, Xiaozhi and Bonsignori, Mattia and Finzi, Andrés and Vandergrift, Nathan  A. and Alam, S.  Munir and Ferrari, Guido and Shen, Xiaoying and Tomaras, Georgia  D. and Kamanga, Gift and Cohen, Myron  S. and Sam, Noel  E. and Kapiga, Saidi and Gray, Elin S. and Tumba, Nancy  L. and Morris, Lynn and Zolla-Pazner, Susan and Gorny, Miroslaw  K. and Mascola, John  R. and Hahn, Beatrice H. and Shaw, George  M. and Sodroski, Joseph  G. and Liao, Hua-Xin and Montefiori, David C. and Hraber, Peter T. and Korber, Bette T. and Haynes, Barton F.},
abstractNote = {The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.},
doi = {10.1016/j.chom.2015.08.006},
url = {https://www.osti.gov/biblio/1233164}, journal = {Cell Host & Microbe},
issn = {1931-3128},
number = 3,
volume = 18,
place = {United States},
year = {Wed Sep 09 00:00:00 EDT 2015},
month = {Wed Sep 09 00:00:00 EDT 2015}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1016/j.chom.2015.08.006
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 52 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

The N276 Glycosylation Site Is Required for HIV-1 Neutralization by the CD4 Binding Site Specific HJ16 Monoclonal Antibody
journal, July 2013

Development of broadly neutralizing antibodies from autologous neutralizing antibody responses in HIV infection
journal, January 2014

Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies
journal, July 2014

Correlation between Immunologic Responses to a Recombinant Glycoprotein 120 Vaccine and Incidence of HIV‐1 Infection in a Phase 3 HIV‐1 Preventive Vaccine Trial
journal, March 2005

Preferential use of the VH5-51 gene segment by the human immune response to code for antibodies against the V3 domain of HIV-1
journal, February 2009

Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus Neutralization Efficiency
journal, November 2013

Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial
journal, April 2012

Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes
journal, April 2010

Neutralizing antibody patterns and viral escape in HIV-1 non-B subtype chronically infected treatment-naive individuals
journal, May 2006

Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants
journal, November 2014

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
journal, April 2013

Evolution of Maternofetal Transport of Immunoglobulins During Human Pregnancy
journal, November 1996

HIV-1 neutralizing antibodies: understanding nature's pathways
journal, June 2013

Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials
journal, May 2012

Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions
journal, October 2014

Neutralization Patterns and Evolution of Sequential HIV Type 1 Envelope Sequences in HIV Type 1 Subtype B-Infected Drug-Naive Individuals
journal, December 2008

Maternal HIV-1 envelope–specific antibody responses and reduced risk of perinatal transmission
journal, June 2015

Rapid evolution of the neutralizing antibody response to HIV type 1 infection
journal, March 2003

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection
journal, June 2009

Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding
journal, July 2011

Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies
journal, November 2009

Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals
journal, August 2011

Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope
journal, August 2014

Antibody neutralization and escape by HIV-1
journal, March 2003

Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies
journal, July 2014

    Sort options
    [ × clear filter / sort ]

    Works referencing / citing this record:

    Two Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV-1-Infected Cells
    journal, November 2018

    Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env
    journal, March 2019

    Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development
    journal, January 2017

    Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller
    journal, January 2017

      Sort options
      [ × clear filter / sort ]

      Similar records in OSTI.GOV collections: