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

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
  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:
OSTI Identifier:
1233164
Report Number(s):
LA-UR--14-24938
Journal ID: ISSN 1931-3128; PII: S1931312815003340
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Cell Host & Microbe
Additional Journal Information:
Journal Volume: 18; Journal Issue: 3; Journal ID: ISSN 1931-3128
Publisher:
Elsevier
Research Org:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES