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Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection.

Publication ,  Journal Article
Hay, CM; Ruhl, DJ; Basgoz, NO; Wilson, CC; Billingsley, JM; DePasquale, MP; D'Aquila, RT; Wolinsky, SM; Crawford, JM; Montefiori, DC; Walker, BD
Published in: J Virol
July 1999

Human immunodeficiency virus type 1 (HIV-1)-specific immune responses over the course of rapidly progressive infection are not well defined. Detailed longitudinal analyses of neutralizing antibodies, lymphocyte proliferation, in vivo-activated and memory cytotoxic T-lymphocyte (CTL) responses, and viral sequence variation were performed on a patient who presented with acute HIV-1 infection, developed an AIDS-defining illness 13 months later, and died 45 months after presentation. Neutralizing-antibody responses remained weak throughout, and no HIV-1-specific lymphocyte proliferative responses were seen even early in the disease course. Strong in vivo-activated CTL directed against Env and Pol epitopes were present at the time of the initial drop in viremia but were quickly lost. Memory CTL against Env and Pol epitopes were detected throughout the course of infection; however, these CTL were not activated in vivo. Despite an initially narrow CTL response, new epitopes were not targeted as the disease progressed. Viral sequencing showed the emergence of variants within the two targeted CTL epitopes; however, viral variants within the immunodominant Env epitope were well recognized by CTL, and there was no evidence of viral escape from immune system detection within this epitope. These data demonstrate a narrowly directed, static CTL response in a patient with rapidly progressive disease. We also show that disease progression can occur in the presence of persistent memory CTL recognition of autologous epitopes and in the absence of detectable escape from CTL responses, consistent with an in vivo defect in activation of CTL.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

July 1999

Volume

73

Issue

7

Start / End Page

5509 / 5519

Location

United States

Related Subject Headings

  • Virology
  • Time Factors
  • T-Lymphocytes, Cytotoxic
  • Phenotype
  • Peptides
  • Neutralization Tests
  • Mutation
  • Male
  • Major Histocompatibility Complex
  • Lymphocytes
 

Citation

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MLA
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Hay, C. M., Ruhl, D. J., Basgoz, N. O., Wilson, C. C., Billingsley, J. M., DePasquale, M. P., … Walker, B. D. (1999). Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection. J Virol, 73(7), 5509–5519. https://doi.org/10.1128/JVI.73.7.5509-5519.1999
Hay, C. M., D. J. Ruhl, N. O. Basgoz, C. C. Wilson, J. M. Billingsley, M. P. DePasquale, R. T. D’Aquila, et al. “Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection.J Virol 73, no. 7 (July 1999): 5509–19. https://doi.org/10.1128/JVI.73.7.5509-5519.1999.
Hay CM, Ruhl DJ, Basgoz NO, Wilson CC, Billingsley JM, DePasquale MP, et al. Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection. J Virol. 1999 Jul;73(7):5509–19.
Hay, C. M., et al. “Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection.J Virol, vol. 73, no. 7, July 1999, pp. 5509–19. Pubmed, doi:10.1128/JVI.73.7.5509-5519.1999.
Hay CM, Ruhl DJ, Basgoz NO, Wilson CC, Billingsley JM, DePasquale MP, D’Aquila RT, Wolinsky SM, Crawford JM, Montefiori DC, Walker BD. Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection. J Virol. 1999 Jul;73(7):5509–5519.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

July 1999

Volume

73

Issue

7

Start / End Page

5509 / 5519

Location

United States

Related Subject Headings

  • Virology
  • Time Factors
  • T-Lymphocytes, Cytotoxic
  • Phenotype
  • Peptides
  • Neutralization Tests
  • Mutation
  • Male
  • Major Histocompatibility Complex
  • Lymphocytes