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Title: Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

Background: therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. As a result, CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodiesmore » that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Finally, our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.« less
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [2] ;  [4] ;  [5] ;  [6] ;  [5] ;  [5] ;  [7] ;  [7] ;  [2] ;  [2]
  1. Univ. of Lisbon (Portugal). School of Pharmacy. Retroviruses and Related Infections Unit. Molecular Pathogenesis Center; Inst. of Health Sciences Egas Moniz, Caparica (Portugal). Interdisciplinary Research Center Egas Moniz (CiiEM)
  2. Univ. of Lisbon (Portugal). School of Pharmacy. Retroviruses and Related Infections Unit. Molecular Pathogenesis Center; Inst. of Health Sciences Egas Moniz, Caparica (Portugal). Interdisciplinary Research Center Egas Moniz (CiiEM)
  3. New Univ. of Lisbon (Portugal). Medical Microbiology Unit. Inst. of Hygiene and Tropical Medicine
  4. Hospital Dona Estefania, Lisbon (Portugal). Immunohematology Unit
  5. Inst. of Health Sciences Egas Moniz, Caparica (Portugal). Interdisciplinary Research Center Egas Moniz (CiiEM)
  6. Inst. of Health Sciences Egas Moniz, Caparica (Portugal). Interdisciplinary Research Center Egas Moniz (CiiEM); Hospital of West Lisbon (Portugal). Lab. of Molecular Biology. Medical Transfusion Service; Inst. of Hygiene and Tropical Medicine, Lisbon (Portugal). Center for Malaria and other Tropical Diseases
  7. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Biology and Biophysics
Publication Date:
OSTI Identifier:
1321725
Report Number(s):
LA-UR--13-20771
Journal ID: ISSN 1742-4690
Grant/Contract Number:
PTDC/SAU-FAR/115290/2009; PTDC/SAU-EPI/122400/2010; R01AI087520; 623-2011-1100
Type:
Accepted Manuscript
Journal Name:
Retrovirology
Additional Journal Information:
Journal Volume: 10; Journal ID: ISSN 1742-4690
Publisher:
BioMed Central
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of Lisbon (Portugal); Inst. of Health Sciences Egas Moniz, Caparica (Portugal)
Sponsoring Org:
Foundation of Science and Technology (FCT) (Portugal); National Inst. of Health (NIH) (United States);European Union (EU); Swedish Research Council (Sweden)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES vertical HIV-2 infection; evolution of the neutralizing antibody response; escape from neutralization; molecular evolution; tropism