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
Abstract
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 »
- Authors:
-
- 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)
- 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)
- New Univ. of Lisbon (Portugal). Medical Microbiology Unit. Inst. of Hygiene and Tropical Medicine
- Hospital Dona Estefania, Lisbon (Portugal). Immunohematology Unit
- Inst. of Health Sciences Egas Moniz, Caparica (Portugal). Interdisciplinary Research Center Egas Moniz (CiiEM)
- 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
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Biology and Biophysics
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (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 (SRC)
- 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
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Retrovirology
- Additional Journal Information:
- Journal Volume: 10; Journal ID: ISSN 1742-4690
- Publisher:
- BioMed Central
- 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
Citation Formats
Rocha, Cheila, Calado, Rita, Borrego, Pedro, Marcelino, José Maria, Bártolo, Inês, Rosado, Lino, Cavaco-Silva, Patrícia, Gomes, Perpétua, Família, Carlos, Quintas, Alexandre, Skar, Helena, Leitner, Thomas, Barroso, Helena, and Taveira, Nuno. 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. United States: N. p., 2013.
Web. doi:10.1186/1742-4690-10-110.
Rocha, Cheila, Calado, Rita, Borrego, Pedro, Marcelino, José Maria, Bártolo, Inês, Rosado, Lino, Cavaco-Silva, Patrícia, Gomes, Perpétua, Família, Carlos, Quintas, Alexandre, Skar, Helena, Leitner, Thomas, Barroso, Helena, & Taveira, Nuno. 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. United States. https://doi.org/10.1186/1742-4690-10-110
Rocha, Cheila, Calado, Rita, Borrego, Pedro, Marcelino, José Maria, Bártolo, Inês, Rosado, Lino, Cavaco-Silva, Patrícia, Gomes, Perpétua, Família, Carlos, Quintas, Alexandre, Skar, Helena, Leitner, Thomas, Barroso, Helena, and Taveira, Nuno. Thu .
"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". United States. https://doi.org/10.1186/1742-4690-10-110. https://www.osti.gov/servlets/purl/1321725.
@article{osti_1321725,
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},
author = {Rocha, Cheila and Calado, Rita and Borrego, Pedro and Marcelino, José Maria and Bártolo, Inês and Rosado, Lino and Cavaco-Silva, Patrícia and Gomes, Perpétua and Família, Carlos and Quintas, Alexandre and Skar, Helena and Leitner, Thomas and Barroso, Helena and Taveira, Nuno},
abstractNote = {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 antibodies 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.},
doi = {10.1186/1742-4690-10-110},
journal = {Retrovirology},
number = ,
volume = 10,
place = {United States},
year = {Thu Oct 24 00:00:00 EDT 2013},
month = {Thu Oct 24 00:00:00 EDT 2013}
}
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