Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of
filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 α/β -/-
interferon receptor-deficient KO mice, strain A129 IFN-α/β -/-, were used to determine the lethality of a range of filoviruses, including Lake Victoria marburgvirus (MARV), Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV),
Reston ebolavirus (REBOV) and Côte d'Ivoire ebolavirus (CIEBOV), administered by using intraperitoneal (IP) or
aerosol routes of
infection. One hundred percent mortality was observed in all groups of KO mice that were administered with a range of challenge doses of MARV and ZEBOV by either IP or
aerosol routes. Mean time to death for both routes was dose-dependent and ranged from 5.4 to 7.4 days in the IP injection challenge, and from 10.2 to 13 days in the
aerosol challenge. The lethal dose (50 % tissue culture infective dose, TCID(50)) of ZEBOV for KO mice was <1 TCID(50) ml(-1) when administered by either the IP or
aerosol route of
infection; for MARV the lethal dose was <1 TCID(50) ml(-1) by the IP route of
infection and <10 TCID(50) ml(-1) by the
aerosol route. In contrast, there was no mortality after
infection with SEBOV or REBOV by either IP or
aerosol routes of
infection; all the mice lost weight (~15 % loss of group mean
body weight with SEBOV and ~7 % with REBOV) but recovered to their original weights by day 14 post-challenge. There was no mortality in mice administered with CIEBOV via the IP route of
infection and no clinical signs of
infection were observed. The progression of disease was faster following
infection with ZEBOV than with MARV but ultimately both viruses caused widespread
infection with high titres of the infectious viruses in multiple organs. Histopathological observations were consistent with other animal models and showed widespread organ damage. This study suggests that MARV and ZEBOV are more virulent when administered via the IP route rather than by
aerosol infection, although both are highly virulent by either route. The KO mouse may provide a useful model to test potential
antiviral therapeutics against wild-type filoviruses.