title: Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.
abstract: BACKGROUND
  Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.
  
  
  METHODS
  We have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.
  
  
  RESULTS
  The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: "full-responders" (positive response against both viral particles), "partial-responders" (positive response only against NL4-3/ΔRT virions) and "non-responders" (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.
  
  
  CONCLUSIONS
  In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay.
authors.affiliation: Retrovirology and Viral Immunopathology Laboratory, Institut d´Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Alberto Crespo
authors.initials: AC
authors.lastname: Guardo
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Fernández
authors.forename: Hodei
authors.initials: H
authors.lastname: Arberas
authors.forename: Javier
authors.initials: J
authors.lastname: García-Pérez
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Manuel Enric
authors.initials: ME
authors.lastname: Bargalló
authors.forename: María José
authors.initials: MJ
authors.lastname: Maleno
authors.forename: José María
authors.initials: JM
authors.lastname: Gatell
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.forename: José
authors.initials: J
authors.lastname: Alcami
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Sánchez-Palomino
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
mesh_terms: D000328:Adult; D000483:Alleles; D058070:Asymptomatic Diseases; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D050296:Microbial Viability / Q000276:immunology; D008875:Middle Aged; D012449:Safety; D012727:Sex Characteristics; D013997:Time Factors; D019562:Viral Load / Q000276:immunology; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology; D014771:Virion / Q000201:enzymology / Q000276:immunology* / Q000502:physiology; D055815:Young Adult
chemical_list: D014765:Viral Vaccines; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase