Cellular immune response to Hantaan virus nucleocapsid protein in the acute phase of hemorrhagic fever with renal syndrome: correlation with disease severity

J Infect Dis. 2009 Jan 15;199(2):188-95. doi: 10.1086/595834.

Abstract

Background: The cellular immune response to Hantaan virus (HTNV) is incompletely understood, especially in humans.

Methods: To investigate the cellular immunity during acute HTNV infection, the magnitude of the CD4(+) and CD8(+) T cell responses to HTNV nucleocapsid protein was quantitated by direct ex vivo interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot analysis, using an array of overlapping peptides.

Results: We found that the combined frequencies of HTNV-specific T cells at the earliest available time point (5-8 days after fever onset) were significantly higher in patients who had mild or moderate hemorrhagic fever with renal syndrome (HFRS) than in those who had severe or critical HFRS (P= .006). Moreover, these frequencies were higher in patients with subsequent mild renal failure (maximum serum creatinine level, <or=707 micromol/L) than in those with subsequent severe renal failure (maximum serum creatinine level, >707 micromol/L) (P= .006). Kinetic analysis showed that a decrease in the serum creatinine level during the acute phase of illness was often accompanied by an increase in the magnitude of IFN-gamma-producing T cells.

Conclusion: Taken together with published data on the similar associations with neutralizing antibody, these data suggest that IFN-gamma-producing T cells may help reduce the risk of progression to acute renal failure caused by HTNV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Capsid Proteins / immunology*
  • China
  • Female
  • Hantaan virus / immunology*
  • Hemorrhagic Fever with Renal Syndrome / immunology*
  • Hemorrhagic Fever with Renal Syndrome / physiopathology
  • Hemorrhagic Fever with Renal Syndrome / virology
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Severity of Illness Index*
  • Viral Core Proteins / immunology*
  • Young Adult

Substances

  • Capsid Proteins
  • Viral Core Proteins
  • nucleocapsid protein, Hantaan virus
  • Interferon-gamma