Cross-reactive Immunity Among Different Serotypes of Virus Causing Haemorrhagic Fever with Renal Syndrome

Spleen cells primed by Prospect Hill (PH) or Puumala (Pu) virus could cross-react with Hantaan virus (HV) 76-118 strain-infected target cells after in vitro stimulation with HV-infected cells, although anti-PH or anti-Pu immune serum showed no cross-reactive neutralizing (NT) activity to HV without complement. These results and our previous findings with cross-reactive cytotoxic T lymphocytes (CTLs) suggest that some epitopes recognized by CTLs might be common among the hantavirus genus, while the epitopes related to NT activity were mainly specific to each virus of this genus. Next, to evaluate the cross-reactive immunities demonstrated by in vitro study, we investigated the effect of transferring T lymphocytes and sera from BALB/c mice immunized with PH or Pu virus into nude mice before HV inoculation. Transferring T lymphocytes primed by PH or Pu virus reduced HV titres in lungs and spleens of nude mice, corresponding with the results of the in vitro CTL assays. Transferring anti-Pu immune serum also decreased HV titres in nude mice, which seemed to reflect complement-dependent NT activity. Moreover ICR mice previously immunized with PH or Pu virus showed resistance to challenge with a lethal dose of the HV KHF strain, indicating that cross-reactive immunity induced by PH or Pu virus could protect ICR mice against pathogenic HV infection.