The antiviral efficacy of HIV-specific [CD8.sup.+] T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate

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  • Additional Information
    • Publication Information:
      Public Library of Science
    • Publication Date:
      2011
    • Subject Terms:
    • Abstract:
      A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted [Nef.sub.90-97] epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A-H) could activate antiviral activity in FL8-specific cytotoxic T-lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef proteins, expressed by HIV-1 isolates or as recombinant vaccinia-Nef, were optimally recognised by CTL. Recognition of the HIV-1 isolates by CTL was independent of clade-grouping but correlated with virusspecific polymorphisms in the epitope flanking region, which altered immunoproteasomal cleavage resulting in enhanced or impaired epitope generation. The finding that the majority of virus isolates failed to present this conserved epitope highlights the importance of viral variance in CTL epitope flanking regions on the efficiency of antigen processing, which has been considerably underestimated previously. This has important implications for future vaccine design strategies since efficient presentation of conserved viral epitopes is necessary to promote enhanced anti-viral immune responses.
    • ISSN:
      1553-7366
    • Rights:
      COPYRIGHT 2011 Public Library of Science
      Copyright 2011 Gale, Cengage Learning. All rights reserved.
    • Accession Number:
      edsgcl.258916189
  • Citations
    • ABNT:
      RANASINGHE, S. R. F. et al. The antiviral efficacy of HIV-specific [CD8.sup.+] T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate. PLoS Pathogens, [s. l.], n. 5, 2011. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580. Acesso em: 14 dez. 2019.
    • AMA:
      Ranasinghe SRF, Kramer HB, Wright C, et al. The antiviral efficacy of HIV-specific [CD8.sup.+] T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate. PLoS Pathogens. 2011;(5). http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580. Accessed December 14, 2019.
    • APA:
      Ranasinghe, S. R. F., Kramer, H. B., Wright, C., Kessler, B. M., Gleria, K. di, Zhang, Y., … Dong, T. (2011). The antiviral efficacy of HIV-specific [CD8.sup.+] T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate. PLoS Pathogens, (5). Retrieved from http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580
    • Chicago/Turabian: Author-Date:
      Ranasinghe, Srinika R.F., Holger B. Kramer, Cynthia Wright, Benedikt M. Kessler, Katalin di Gleria, Yonghong Zhang, Geraldine M. Gillespie, et al. 2011. “The Antiviral Efficacy of HIV-Specific [CD8.Sup.+] T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate.” PLoS Pathogens, no. 5. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580.
    • Harvard:
      Ranasinghe, S. R. F. et al. (2011) ‘The antiviral efficacy of HIV-specific [CD8.sup.+] T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate’, PLoS Pathogens, (5). Available at: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580 (Accessed: 14 December 2019).
    • Harvard: Australian:
      Ranasinghe, SRF, Kramer, HB, Wright, C, Kessler, BM, Gleria, K di, Zhang, Y, Gillespie, GM, Blais, M-E, Culshaw, A, Pichulik, T, Simmons, A, Rowland-Jones, SL, McMichael, AJ & Dong, T 2011, ‘The antiviral efficacy of HIV-specific [CD8.sup.+] T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate’, PLoS Pathogens, no. 5, viewed 14 December 2019, .
    • MLA:
      Ranasinghe, Srinika R. F., et al. “The Antiviral Efficacy of HIV-Specific [CD8.Sup.+] T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate.” PLoS Pathogens, no. 5, 2011. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580.
    • Chicago/Turabian: Humanities:
      Ranasinghe, Srinika R.F., Holger B. Kramer, Cynthia Wright, Benedikt M. Kessler, Katalin di Gleria, Yonghong Zhang, Geraldine M. Gillespie, et al. “The Antiviral Efficacy of HIV-Specific [CD8.Sup.+] T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate.” PLoS Pathogens, no. 5 (2011). http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580.
    • Vancouver/ICMJE:
      Ranasinghe SRF, Kramer HB, Wright C, Kessler BM, Gleria K di, Zhang Y, et al. The antiviral efficacy of HIV-specific [CD8.sup.+] T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate. PLoS Pathogens [Internet]. 2011 [cited 2019 Dec 14];(5). Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsgsc&AN=edsgcl.258916189&custid=s6224580