Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques

Katherine M. Mladinich, Shari M. Piaskowski, Richard Rudersdorf, Christopher M. Eernisse, Kim L. Weisgrau, Mauricio Martins, Jessica R. Furlott, Charalambos D. Partidos, Joseph N. Brewoo, Jorge E. Osorio, Nancy A. Wilson, Eva G. Rakasz, David Watkins

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Every year, Dengue virus (DENV) infects approximately 100 million people. There are currently several vaccines undergoing clinical studies, but most target the induction of neutralizing antibodies. Unfortunately, DENV infection can be enhanced by subneutralizing levels of antibodies that bind virions and deliver them to cells of the myeloid lineage, thereby increasing viral replication (termed antibody-dependent enhancement [ADE]). T lymphocyte-based vaccines may offer an alternative that avoids ADE. The goal of our study was to describe the cellular immune response generated after primary DENV infection in Indian rhesus macaques. We infected eight rhesus macaques with 105 plaque-forming units (PFU) of DENV serotype 2 (DENV2) New Guinea C (NGC) strain, and monitored viral load and the cellular immune response to the virus. Viral replication peaked at day 4 post-infection and was resolved by day 10. DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia. DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β). In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a. Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic. Our results provide a more complete understanding of the cellular immune response during DENV infection in rhesus macaques and contribute to the development of rhesus macaques as an animal model for DENV vaccine and pathogenicity studies.

Original languageEnglish
Pages (from-to)111-121
Number of pages11
JournalImmunogenetics
Volume64
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Fingerprint

Dengue Virus
Macaca mulatta
T-Lymphocytes
Antibody-Dependent Enhancement
Virus Diseases
Cellular Immunity
Chemokine CCL4
Interferon-gamma
Dengue Vaccines
Vaccines
Tumor Necrosis Factor-alpha
New Guinea
Viremia
Cell Lineage
Neutralizing Antibodies
Viral Load
Virion
Interleukin-2
Virulence
Animal Models

Keywords

  • CD8 and CD4 T lymphocytes
  • Dengue
  • Indian rhesus macaque

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques. / Mladinich, Katherine M.; Piaskowski, Shari M.; Rudersdorf, Richard; Eernisse, Christopher M.; Weisgrau, Kim L.; Martins, Mauricio; Furlott, Jessica R.; Partidos, Charalambos D.; Brewoo, Joseph N.; Osorio, Jorge E.; Wilson, Nancy A.; Rakasz, Eva G.; Watkins, David.

In: Immunogenetics, Vol. 64, No. 2, 01.02.2012, p. 111-121.

Research output: Contribution to journalArticle

Mladinich, KM, Piaskowski, SM, Rudersdorf, R, Eernisse, CM, Weisgrau, KL, Martins, M, Furlott, JR, Partidos, CD, Brewoo, JN, Osorio, JE, Wilson, NA, Rakasz, EG & Watkins, D 2012, 'Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques', Immunogenetics, vol. 64, no. 2, pp. 111-121. https://doi.org/10.1007/s00251-011-0566-0
Mladinich, Katherine M. ; Piaskowski, Shari M. ; Rudersdorf, Richard ; Eernisse, Christopher M. ; Weisgrau, Kim L. ; Martins, Mauricio ; Furlott, Jessica R. ; Partidos, Charalambos D. ; Brewoo, Joseph N. ; Osorio, Jorge E. ; Wilson, Nancy A. ; Rakasz, Eva G. ; Watkins, David. / Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques. In: Immunogenetics. 2012 ; Vol. 64, No. 2. pp. 111-121.
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