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The nervous system in genital herpes simplex virus type 2 infections in mice. Lethal panmyelitis or nonlethal
Abstract:
Female mice were inoculated vaginally with the MS strain of herpes simplex virus type 2, and serially positive vaginal cultures were used to confirm infection. The proportion of mice infected and the mortality rate in infected mice decreased with increasing age. In mice 12 weeks old, clinical, neuropathologic, and virologic criteria defined four patterns of disease. Moribund mice had severe genital lesions, hindleg paralysis, and urinary and fecal retention, and most died during the second week of infection. These mice had a panmyelitis with a decreasing gradient of both viral antigen and lesions extending rostrally from the lumbosacral cord into the brain stem. Lesions were about equally distributed in gray and white matter and were characterized by neuronal loss and axonal demyelination, respectively. By contrast, mice with nonfatal infections had mild or no evident genital lesions and a small proportion had mild hindleg weakness. Of these, some mice had demyelinative lesions, particularly in the lower spinal cord but also at higher cord and brain stem levels, whereas others had leptomeningitis. Both of these groups had sacral sensory root abnormalities. A third group of survivors lacked both sensory root and central nervous system abnormalities. This report defines a broader spectrum of disease patterns following infection by a natural route than has been previously appreciated. It provides the first evidence that nonfatal herpes simplex virus type 2 infection by a peripheral route can produce central nervous system demyelination. It indicates that in aseptic meningitis with this agent, the route of virus spread to the central nervous system is neural and not hematogenous. Finally, the antigenic and pathologic observations presented here complement and confirm the virus isolation data and pathologic findings of others that genital herpes simplex virus type 2 infection causes ascending infection in the peripheral and central nervous system.
Insights
Herpes simplex virus type 2 (HSV-2) infection in mice shows varied disease patterns, with older mice experiencing less severe outcomes. This study reveals HSV-2 can cause central nervous system demyelination via neural spread, even in nonfatal peripheral infections.
Area of Science:
- Virology
- Neurology
- Immunology
Background:
- Herpes simplex virus type 2 (HSV-2) is a common human pathogen.
- Understanding HSV-2 pathogenesis, particularly its neurological complications, is crucial.
- Previous studies have not fully elucidated the spectrum of disease following natural route infection.
Purpose of the Study:
- To define the spectrum of disease patterns in female mice infected vaginally with HSV-2.
- To investigate the neuropathogenesis of HSV-2 infection, including central nervous system involvement.
- To determine the route of HSV-2 spread to the central nervous system.
Main Methods:
- Vaginal inoculation of female mice with the MS strain of HSV-2.
- Serial vaginal cultures to confirm infection.
- Clinical, neuropathologic, and virologic assessments of infected mice at 12 weeks old.
Main Results:
- Infection and mortality rates decreased with increasing age.
- Four distinct disease patterns were identified in 12-week-old mice, ranging from fatal panmyelitis to nonfatal demyelinative lesions and aseptic meningitis.
- Nonfatal peripheral HSV-2 infection demonstrated the capacity to induce central nervous system demyelination, with evidence of neural spread.
Conclusions:
- HSV-2 infection in mice presents a broader spectrum of disease than previously recognized.
- Peripheral HSV-2 infection can lead to central nervous system demyelination through neural pathways.
- Aseptic meningitis associated with HSV-2 likely results from neural rather than hematogenous spread.