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

Journal Article · · Cell Host & Microbe
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  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)
+ Show Author Affiliations

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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1233164
Report Number(s):
LA-UR-14-24938; PII: S1931312815003340
Journal Information:
Cell Host & Microbe, Vol. 18, Issue 3; ISSN 1931-3128
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 52 works
Citation information provided by
Web of Science

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Cited By (6)

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
Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization journal July 2016
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
Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk journal February 2017

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