Cellular Immune Response to Hantaan Virus Nucleocapsid Protein in the Acute Phase of Hemorrhagic Fever with Renal Syndrome: Correlation with Disease Severity

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.