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Published on: October 17, 2018
POLIOMYELITIS IN THE CYNOMOLGUS MONKEY : II. RESISTANCE TO SPREAD OF INFECTION IN THE CENTRAL NERVOUS SYSTEM
H K Faber1, R J Silverberg, L Dong
1Department of Pediatrics, Stanford University School of Medicine, San Francisco.
Abstract:
1. Repeated non-traumatic exposures to poliomyelitis virus of the mucous membranes of the upper respiratory tract and of various portions of the alimentary tract in 5 cynomolgus monkeys, extending over a period of 9 to 14 months, were followed by a definite, though limited resistance to intracerebral inoculation to the homologous strain of virus in 4 of them. Only one monkey developed paralysis (20 per cent incidence) and the other 4 remained free of signs and symptoms of the disease. 92 per cent of 25 previously untreated monkeys developed paralysis with the same strain after intracerebral inoculation. 2. Microscopic examination of the central and peripheral nervous systems of the 4 non-paralytic cases revealed in all instances typical lesions in the central nervous system descending from the level of inoculation into the brain-stem but in only 2 into the spinal cord and then only in limited, small areas. Lesions were found in the peripheral ganglia in all animals which corresponded in distribution with the surface membranes previously exposed to virus. No lesions were found in the central nervous system indicative of invasion preceding the intracerebral inoculation. 3. Our observations point to the acquisition by the immune animal, as a result of surface exposure, of the power to limit the spread of infection in the central nervous system rather than of the capacity entirely to prevent implantation and multiplication of virus. 4. This limitation of spread, it is suggested, resembles the tendency so commonly seen in human poliomyelitis of the disease to "halt" at some stage of its evolution, resulting in the various clinical gradations in extent and severity of involvement (subclinical, abortive, non-paralytic, mild paralytic forms, etc.) 5. The experimental methods of exposure, previous to intracerebral inoculation, employed in our study are compared with the natural exposures of human beings during the course of life, which, as age advances, lead to increasing resistance to poliomyelitis and to an increasing incidence of specific neutralizing antibodies in the blood. 6. The mechanism of resistance is obscure. It may be related to the continuing presence of infection in the peripheral ganglia but this is as yet unproved.
Insights
Repeated surface exposure to poliovirus in monkeys created limited resistance to paralysis. This suggests natural poliovirus exposure may help limit disease spread in humans, similar to observed clinical variations.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Poliomyelitis poses a significant public health challenge, necessitating a deeper understanding of host resistance mechanisms.
- Previous research indicates that natural exposure to poliovirus can confer some level of immunity.
- The precise mechanisms by which the host immune system limits poliovirus infection and disease progression remain incompletely understood.
Purpose of the Study:
- To investigate the development of resistance to poliovirus following repeated non-traumatic mucosal exposure in a primate model.
- To elucidate the pathological changes in the nervous system associated with limited poliovirus infection.
- To explore the implications of these findings for understanding natural resistance to poliomyelitis in humans.
Main Methods:
- Cynomolgus monkeys were subjected to repeated non-traumatic exposure of poliovirus to the upper respiratory and alimentary tracts over 9-14 months.
- Following the exposure period, monkeys were intracerebrally inoculated with a homologous poliovirus strain.
- Neuropathological examination of the central and peripheral nervous systems was conducted on non-paralytic cases.
Main Results:
- Four out of five monkeys exhibited limited resistance, with only one developing paralysis (20% incidence) compared to 92% in untreated controls.
- Microscopic examination revealed central nervous system lesions descending from the inoculation site, but limited in spread.
- Peripheral ganglia showed lesions corresponding to prior surface exposure sites, with no evidence of prior central nervous system invasion.
Conclusions:
- Surface exposure to poliovirus confers a limited capacity to restrict the spread of infection within the central nervous system.
- This observed limitation in viral spread may explain the varied clinical presentations of poliomyelitis in humans, from subclinical to paralytic forms.
- The findings suggest that natural exposures contribute to increasing resistance to poliomyelitis with age, potentially through mechanisms involving peripheral ganglia.
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