Document Detail


Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism.
MedLine Citation:
PMID:  23151495     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES:: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients. METHODS:: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma immunoglobulin G (IgG) antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor usage was determined in ghost cells. The sequence and predicted three-dimensional structure of the C2V3C3 Env region were determined for all isolates. RESULTS:: Only 50% of the patients consistently produced IgG NAbs to autologous and contemporaneous virus isolates. In contrast, 96% of the patients produced IgG antibodies that neutralized at least two isolates of a panel of six heterologous R5 isolates. Breadth and potency of the neutralizing antibodies were positively associated with the number of CD4 T cells and with the titer and avidity of C2V3C3-specific binding IgG antibodies. X4 isolates were obtained only from late stage disease patients and were fully resistant to neutralization. The V3 loop of X4 viruses was longer, had a higher net charge, and differed markedly in secondary structure compared to R5 viruses. CONCLUSION:: Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific neutralizing antibodies whose potency and breadth decreases as the disease progresses. Resistance to antibody neutralization occurs in late stage disease and is usually associated with X4 viral tropism and major changes in V3 sequence and conformation. Our studies support a model of HIV-2 pathogenesis in which the neutralizing antibodies play a central role and have clear implications for the vaccine field.
Authors:
José M Marcelino; Pedro Borrego; Charlotta Nilsson; Carlos Família; Helena Barroso; Fernando Maltez; Manuela Doroana; Francisco Antunes; Alexandre Quintas; Nuno Taveira
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Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  AIDS (London, England)     Volume:  26     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  -    
Other Details:
Languages:  ENG     Pagination:  2275-2284     Citation Subset:  -    
Affiliation:
aUnidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon bCentro de Investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica cUnidade de Retrovírus e Infecções Associadas, Centro de Patogénese Molecular, Faculdade de Farmácia de Lisboa, Lisbon, Portugal dDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet and Swedish Institute for Communicable Disease Control, Solna, Sweden eServiço de Doenças Infecciosas, Hospital de Curry Cabral fServiço de Doenças Infecciosas, Hospital de Santa Maria, Lisbon, Portugal.
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