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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

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 » 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:
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 (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. 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, 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. doi: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 = {2013},
month = {10}
}

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Works referenced in this record:

HIV-2: the forgotten AIDS virus
journal, December 2008

  • de Silva, Thushan I.; Cotten, Matthew; Rowland-Jones, Sarah L.
  • Trends in Microbiology, Vol. 16, Issue 12
  • DOI: 10.1016/j.tim.2008.09.003

A call for randomized controlled trials of antiretroviral therapy for HIV-2 infection in West Africa
journal, January 2008


Sequence Note: Identification of a New HIV-2 Subtype Based on Phylogenetic Analysis of Full-Length Genomic Sequence
journal, June 2000

  • Aguchi, Julie Yam; Devare, Sushil G.; Brennan, Catherine A.
  • AIDS Research and Human Retroviruses, Vol. 16, Issue 9
  • DOI: 10.1089/08892220050042864

Identification of a Highly Divergent HIV Type 2 and Proposal for a Change in HIV Type 2 Classification
journal, June 2004

  • Damond, Florence; Worobey, Michael; Campa, Pauline
  • AIDS Research and Human Retroviruses, Vol. 20, Issue 6
  • DOI: 10.1089/0889222041217392

Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia
journal, January 2002


Update on Human Immunodeficiency Virus (HIV)-2 Infection
journal, March 2011

  • Campbell-Yesufu, O. T.; Gandhi, R. T.
  • Clinical Infectious Diseases, Vol. 52, Issue 6
  • DOI: 10.1093/cid/ciq248

Factors associated with clinical progression in HIV-2 infected-patients: The French ANRS cohort
journal, January 2003


Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village
journal, January 2010

  • van der Loeff, Maarten; Larke, Natasha; Kaye, Steve
  • Retrovirology, Vol. 7, Issue 1
  • DOI: 10.1186/1742-4690-7-46

Rate of Decline of Percentage CD4+ Cells Is Faster in HIV-1 Than in HIV-2 Infection
journal, January 1997

  • Jaffar, S.; Wilkins, A.; Ngom, P. T.
  • Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 16, Issue 5
  • DOI: 10.1097/00042560-199712150-00003

Serial CD4 and CD8 T-Lymphocyte Counts and Associated Mortality in an HIV-2-Infected Population in Guinea-Bissau
journal, January 1996

  • Lisse, Ida Maria; Poulsen, Anne-Grethe; Aaby, Peter
  • Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 13, Issue 4
  • DOI: 10.1097/00042560-199612010-00009

Low Plasma Human Immunodeficiency Virus Type 2 Viral Load Is Independent of Proviral Load: Low Virus Production In Vivo
journal, February 2000


Reduced rate of disease development after HIV-2 infection as compared to HIV-1
journal, September 1994


Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France
journal, January 2008


Envelope-specific antibody response in HIV-2 infection: C2V3C3-specific IgG response is associated with disease progression
journal, January 2008


Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1
journal, November 2011

  • Ozkaya Sahin, G.; Holmgren, B.; da Silva, Z.
  • Journal of Virology, Vol. 86, Issue 2
  • DOI: 10.1128/JVI.06315-11

Potent Autologous and Heterologous Neutralizing Antibody Responses Occur in HIV-2 Infection across a Broad Range of Infection Outcomes
journal, November 2011

  • de Silva, T. I.; Aasa-Chapman, M.; Cotten, M.
  • Journal of Virology, Vol. 86, Issue 2
  • DOI: 10.1128/JVI.06126-11

Autologous Neutralizing Antibodies Prevail in HIV-2 but Not in HIV-1 Infection
journal, March 1993

  • Björling, Ewa; Scarlatti, Gabriella; von Gegerfelt, Agneta
  • Virology, Vol. 193, Issue 1
  • DOI: 10.1006/viro.1993.1160

Broad and Potent Neutralizing Antibody Responses Elicited in Natural HIV-2 Infection
journal, October 2011

  • Kong, R.; Li, H.; Bibollet-Ruche, F.
  • Journal of Virology, Vol. 86, Issue 2
  • DOI: 10.1128/JVI.06155-11

Baseline susceptibility of primary HIV-2 to entry inhibitors
journal, January 2012

  • Borrego, Pedro; Calado, Rita; Marcelino, José M.
  • Antiviral Therapy, Vol. 17, Issue 3
  • DOI: 10.3851/IMP1996

Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
journal, January 2012


HIV-2 Genetic Evolution in Patients with Advanced Disease Is Faster than That in Matched HIV-1 Patients
journal, May 2010

  • Skar, Helena; Borrego, Pedro; Wallstrom, Timothy C.
  • Journal of Virology, Vol. 84, Issue 14
  • DOI: 10.1128/JVI.02548-09

The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients
journal, January 2008


Epitope Mapping of Broadly Neutralizing HIV-2 Human Monoclonal Antibodies
journal, August 2012


Phylogenetic Demonstration of Two Cases of Perinatal Human Immunodeficiency Virus Type 2 Infection Diagnosed in Adulthood
journal, December 2004

  • Barroso, Helena; Araújo, Fernando; Gomes, Maria Helena
  • AIDS Research and Human Retroviruses, Vol. 20, Issue 12
  • DOI: 10.1089/aid.2004.20.1373

Vertical transmission of HIV-2
journal, January 1997


Assessment of mother-to-child HIV-1 and HIV-2 transmission: an AIDS reference laboratory collaborative study
journal, March 2009


Perinatally acquired HIV-2 infection diagnosed at 15 and 24 years of age
journal, January 2001


Mother‐to‐Child Transmission of HIV‐2 Infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF‐CO1
journal, October 2010

  • Burgard, M.; Jasseron, C.; Matheron, S.
  • Clinical Infectious Diseases, Vol. 51, Issue 7
  • DOI: 10.1086/656284

Molecular Determinants of HIV-2 R5-X4 Tropism in the V3 Loop: Development of a New Genotypic Tool
journal, December 2011

  • Visseaux, B.; Hurtado-Nedelec, M.; Charpentier, C.
  • Journal of Infectious Diseases, Vol. 205, Issue 1
  • DOI: 10.1093/infdis/jir698

Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation
journal, December 2005

  • Shi, Yu; Brandin, Eleonor; Vincic, Elzbieta
  • Journal of General Virology, Vol. 86, Issue 12
  • DOI: 10.1099/vir.0.81259-0

Small Amino Acid Changes in the V3 Loop of Human Immunodeficiency Virus Type 2 Determines the Coreceptor Usage for CXCR4 and CCR5
journal, November 1999


Clinical Progression in Early and Late Stages of Disease in a Cohort of Individuals Infected with Human Immunodeficiency Virus-2 in Guinea-Bissau
journal, January 2003

  • Norrgren, Hans; Da Silva, Zacarias; Biague, Antonio
  • Scandinavian Journal of Infectious Diseases, Vol. 35, Issue 4
  • DOI: 10.1080/00365540310000210

In vitro replication capacity of HIV-2 variants from long-term aviremic individuals
journal, September 2006


Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant
journal, December 2005


Genetic variation in mother???child acute seroconverter pairs from Zambia
journal, January 2008


Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants
journal, February 2010


Deciphering Human Immunodeficiency Virus Type 1 Transmission and Early Envelope Diversification by Single-Genome Amplification and Sequencing
journal, February 2008

  • Salazar-Gonzalez, J. F.; Bailes, E.; Pham, K. T.
  • Journal of Virology, Vol. 82, Issue 8
  • DOI: 10.1128/JVI.02660-07

A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies
journal, May 2012

  • Doria-Rose, N. A.; Georgiev, I.; O'Dell, S.
  • Journal of Virology, Vol. 86, Issue 15
  • DOI: 10.1128/JVI.00696-12

Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection
journal, December 2005

  • Frost, S. D. W.; Wrin, T.; Smith, D. M.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 51
  • DOI: 10.1073/pnas.0504658102

Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways
journal, September 2009


Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy
journal, September 2010

  • Marcelino, José Maria; Borrego, Pedro; Rocha, Cheila
  • Journal of Virology, Vol. 84, Issue 23
  • DOI: 10.1128/JVI.01102-10

Increased Frequency of Circulating CCR5+ CD4+ T Cells in Human Immunodeficiency Virus Type 2 Infection
journal, October 2006

  • Soares, Rui; Foxall, Russell; Albuquerque, Adriana
  • Journal of Virology, Vol. 80, Issue 24
  • DOI: 10.1128/JVI.01557-06

Clustal W and Clustal X version 2.0
journal, September 2007


MODELTEST: testing the model of DNA substitution
journal, October 1998


Dynamic Correlation between Intrahost HIV-1 Quasispecies Evolution and Disease Progression
journal, December 2008


Datamonkey: rapid detection of selective pressure on individual sites of codon alignments
journal, February 2005


Not So Different After All: A Comparison of Methods for Detecting Amino Acid Sites Under Selection
journal, February 2005

  • Kosakovsky Pond, Sergei L.; Frost, Simon D. W.
  • Molecular Biology and Evolution, Vol. 22, Issue 5
  • DOI: 10.1093/molbev/msi105

BEAST: Bayesian evolutionary analysis by sampling trees
journal, January 2007


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

  • Wei, Xiping; Decker, Julie M.; Wang, Shuyi
  • Nature, Vol. 422, Issue 6929
  • DOI: 10.1038/nature01470

The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling
journal, November 2005


SWISS-MODEL: an automated protein homology-modeling server
journal, July 2003


    Works referencing / citing this record:

    Evolution of HIV-1 within untreated individuals and at the population scale in Uganda
    journal, July 2018