International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 92 - SUSCEPTIBILITY OF INBRED MICE TO FATAL INFECTION BY MOUSE ADENOVIRUS TYPE 1

Spindler KR, Welton AR

University of Michigan, Ann Arbor, United States

Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in inbred and outbred mice.  Aspects of the host immune response important for control of MAV-1 infection include T and B cell function and the antiviral cytokines IFN-g and IFN-a/b   Infection of immunodeficient mice can result in pneumonia, hepatitis, encephalitis, gastroenteritis, and disseminated disease involving multiple organs.  These resemble the disease phenotypes occurring in infection of immunocompromised people; the incidence of human adenovirus disease is increasing with the increased number of immunosuppressed patients, particularly pediatric bone marrow transplant recipients.  Identifying host factors involved in susceptibility to adenovirus infections is thus of importance in transplantation and also because of projected uses of adenovirus vectors in cancer treatments.  Study of human adenoviruses in animal hosts is not possible due to the species-specific nature of adenoviruses. 

MAV-1 is an excellent model for studying susceptibility, because there are significant differences in susceptibility to MAV-1 in different inbred mouse strains. 

SJL/J mice are susceptible to MAV-1, succumbing to a low dose infection 8-10 days post infection with high virus loads in the brain and with a 50% lethal dose (LD50) more than 4 log units lower than other strains of mice, including C3H/HeJ, BALB/cJ, 129/SvEv, and C57BL/6J (1).  When resistant mice are sublethally irradiated, they become susceptible to MAV-1 infection. Primary embryo fibroblasts and primary peritoneal macrophages from resistant and susceptible mice produce equal yields of MAV-1 when infected in culture.  These data suggest that systemic factors, such as components of the innate or adaptive immune system, play a role in MAV-1 susceptibility.  Congenic strains of mice that differed only in their H-2 haplotype were tested for susceptibility, and the results indicated that H-2 or closely linked genes are not a factor in susceptibility to MAV‑1.  Infection of (BALB/cJ x SJL/J)F1 indicated that susceptibility is semidominant.  A genome scan analysis of a 200 mouse (BALB/cJ x SJL/J)F1 x BALB/cJ backcross panel is in progress to develop a low resolution linkage map for susceptibility to MAV-1.  Identification of the gene(s) involved in MAV-1 susceptibility will provide important insight into the contribution of host factors to viral infection.

(1) Spindler, K. R., Fang, L., Moore, M. L., Brown, C. C., Hirsch, G. N., and Kajon, A. K. (2001). J. Virol. 75, 12039-12046.

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