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Modeling Powassan virus infection in Peromyscus leucopus, a natural host
Luwanika Mlera1, Kimberly Meade-White2, Greg Saturday2
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United States of America.
Abstract:
The tick-borne flavivirus, Powassan virus (POWV) causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi), suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5) of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study.
Insights
Peromyscus leucopus mice infected with Powassan virus (POWV) show limited central nervous system infection and control the virus without clinical signs. This suggests natural resistance mechanisms are at play in these mice.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Powassan virus (POWV) is a tick-borne flavivirus causing severe human encephalitis in North America and Europe.
- Ixodid ticks transmit POWV, utilizing small to medium-sized mammals, like Peromyscus leucopus mice, as hosts.
Purpose of the Study:
- To investigate the susceptibility and immune response of Peromyscus leucopus mice to POWV infection.
- To compare the pathogenicity of POWV in Peromyscus leucopus mice versus standard laboratory mouse strains (C57BL/6 and BALB/c).
Main Methods:
- Peromyscus leucopus, C57BL/6, and BALB/c mice were inoculated with POWV via intraperitoneal and intracranial routes.
- Mice were monitored for clinical signs, survival rates, seroconversion, and subjected to histopathological examination of the brain and spinal cord.
Main Results:
- Intracranial POWV inoculation in Peromyscus leucopus mice did not cause clinical disease but induced seroconversion and mild central nervous system inflammation (lymphocytic perivascular cuffing, microgliosis).
- In contrast, intracranial inoculation was lethal in C57BL/6 and BALB/c mice by 5 days post-infection.
- Intraperitoneal inoculation was lethal in BALB/c mice, with a 40% survival rate in C57BL/6 mice.
Conclusions:
- Peromyscus leucopus mice control lethal doses of POWV, exhibiting restricted central nervous system infection and mounting an antibody response without developing overt disease.
- These findings suggest the presence of restriction factors in Peromyscus leucopus mice that limit POWV replication and pathogenesis.
- Further research is needed to elucidate the specific mechanisms underlying POWV restriction in Peromyscus leucopus mice.
