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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
STUDIES IN RODENT POLIOMYELITIS : I. FURTHER EXPERIMENTS WITH THE MURINE STRAIN OF SK POLIOMYELITIS VIRUS
C W Jungeblut1, M Sanders, R R Feiner
1Department of Bacteriology, College of Physicians and Surgeons, Columbia University, New York.
Abstract:
1. SK murine virus maintained over more than 200 serial mouse passages increased in virulence for mice from an initial intracerebral titer of about 1:1 million to a maximum titer of not less than 1:1 billion dilution activity. 2. Following intracerebral injection with murine virus of remote mouse passages, 5 of 13 rhesus monkeys developed a characteristic encephalitic syndrome. Repeated intravenous injection of massive doses of virus caused localized flaccid paralysis in 2 of 14 monkeys. 3. Intracerebral injection of graded doses of murine virus into mice of different age groups caused fatal paralysis in young and old animals alike. Infection with small doses of virus by peripheral routes, while uniformly fatal to young mice, was followed by survival of almost half of the old mice. 4. The incubation period of the disease in young mice infected intracerebrally with a standard dose of murine virus, when studied throughout the period of 1 year, was found considerably lengthened during the summer months. 5. Cross neutralization tests furnished no evidence for any serological relationship between SK murine virus and lymphocytic choriomeningitis virus. Theiler's virus was found to be neutralizable by antimurine horse serum and, to a lesser extent, by concentrated antipoliomyelitis horse serum; however, such inactivation, in both cases, was distinctly inferior to that occurring with SK murine virus. On the other hand, no neutralization whatsoever was obtained between SK murine virus and normal adult mouse serum, whereas the same serum completely neutralized Theiler's virus. Mice surviving infection with Theiler's virus, though acquiring immunity to this virus, remained fully susceptible to reinfection with SK murine virus. 6. Neutralization tests with SK murine virus against poliomyelitis-convalescent monkey sera gave irregular results, but neutralization of murine virus occurred regularly with a hyperimmune antipoliomyelitis horse serum. Hyperimmune antimurine horse and rabbit sera, on the other hand, failed to inactivate three strains of monkey poliomyelitis virus (SK, RMV, Aycock) by intracerebral tests in monkeys. The same sera inactivated murine virus in mice by intraperitoneal, but not by intracerebral injection of virus-serum mixtures. 7. The identity of SK murine virus and its relation to other rodent strains of poliomyelitis virus is discussed on the basis of the available data.
Insights
SK murine virus demonstrated increased virulence in mice after serial passages. This virus also caused neurological disease in rhesus monkeys and showed distinct serological properties differentiating it from other viruses.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- SK murine virus is a significant pathogen in laboratory mice.
- Understanding its virulence and antigenic properties is crucial for disease control and research.
Purpose of the Study:
- To investigate the increased virulence of SK murine virus after serial mouse passages.
- To determine the effects of SK murine virus infection in non-murine species, specifically rhesus monkeys.
- To elucidate the serological relationship of SK murine virus to other known viruses, including poliomyelitis and lymphocytic choriomeningitis virus.
Main Methods:
- Serial passage of SK murine virus in mice to assess virulence changes.
- Intracerebral and intravenous inoculation of rhesus monkeys with the virus.
- Infection of mice of different age groups via intracerebral and peripheral routes.
- Incubation period studies in mice under varying seasonal conditions.
- Cross-neutralization tests using antisera against SK murine virus, Theiler's virus, and poliomyelitis virus strains.
Main Results:
- SK murine virus exhibited a significant increase in virulence (up to 1:1 billion dilution activity) after over 200 mouse passages.
- Intracerebral inoculation induced an encephalitic syndrome in 5/13 rhesus monkeys, while intravenous injection caused paralysis in 2/14.
- Age-dependent susceptibility was observed in mice; young mice were uniformly susceptible to peripheral infection, while older mice showed higher survival rates.
- The incubation period in young mice was longer during summer months.
- SK murine virus showed no serological relationship with lymphocytic choriomeningitis virus. It was partially neutralized by anti-Theiler's and anti-poliomyelitis sera, but distinct differences were noted compared to SK murine virus neutralization.
- Hyperimmune anti-poliomyelitis horse serum neutralized SK murine virus, but hyperimmune anti-murine sera failed to inactivate monkey poliomyelitis virus strains.
Conclusions:
- SK murine virus demonstrates enhanced virulence and neurotropic potential after prolonged passage in mice.
- The virus induces distinct neurological syndromes in non-murine primates, suggesting potential zoonotic implications or shared mechanisms of pathogenesis.
- Serological distinctiveness from lymphocytic choriomeningitis virus and partial cross-reactivity with poliomyelitis virus components warrant further investigation into its classification and relationship with other enteroviruses.
