title: Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal.
authors.forename: José M
authors.initials: JM
authors.lastname: Marcelino
authors.forename: Pedro
authors.initials: P
authors.lastname: Borrego
authors.forename: Charlotta
authors.initials: C
authors.lastname: Nilsson
authors.forename: Carlos
authors.initials: C
authors.lastname: Família
authors.forename: Helena
authors.initials: H
authors.lastname: Barroso
authors.forename: Fernando
authors.initials: F
authors.lastname: Maltez
authors.forename: Manuela
authors.initials: M
authors.lastname: Doroana
authors.forename: Francisco
authors.initials: F
authors.lastname: Antunes
authors.forename: Alexandre
authors.initials: A
authors.lastname: Quintas
authors.forename: Nuno
authors.initials: N
authors.lastname: Taveira
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008297:Male; D009500:Neutralization Tests / Q000379:methods*; D011174:Portugal; D019718:Receptors, CXCR4 / Q000276:immunology*; D056189:Viral Tropism / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4