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MS strain of type 2 herpes simplex virus produces necrotizing retinitis in mice
S Love1, T J Hill, N J Maitland
1Department of Pathology & Microbiology, University of Bristol, UK.
Abstract:
Intracerebral inoculation of mice with the MS strain of type 2 herpes simplex virus (HSV-2) causes a brief encephalitis associated with multifocal central nervous system demyelination. Many of the mice develop unilateral or bilateral impairment of the pupillary light reflex. We have examined the development of ocular disease in inbred NIH mice inoculated intracerebrally with a low dose (10 pfu) of HSV-2 (MS). The resulting acute encephalitis was fatal in 30-50% of the mice. By 1 month after inoculation, the pupillary response to light was absent or impaired in approximately 80% of the surviving mice. Infectious virus could be isolated from the trigeminal ganglia and optic nerves from day 2 and from the eyes by day 4. Viral antigen was first immunohistochemically detectable in the optic nerves on day 5 and in the retinae on day 6. During the second week after inoculation up to half of the mice developed unilateral or bilateral necrotising retinitis associated with high titres of virus in the eyes and abundant viral antigen in the retinae. Electron microscopy confirmed the presence of viral particles in the retinae, in glia and degenerating neurons. No viral antigen was detected in the corneas and only rarely was antigen found in the ciliary body or iris. Infectious virus persisted longer in the eyes than in the trigeminal ganglia or optic nerves and could still be isolated from a few of the animals 2 weeks after inoculation. By 1 month the titres of virus within the eyes had fallen to undetectable levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Herpes simplex virus type 2 (HSV-2) infection in mice causes encephalitis and significant ocular disease, including impaired pupillary light reflex and necrotizing retinitis. This study details the progression of HSV-2 ocular pathology in mice.
Area of Science:
- Neurovirology
- Ophthalmology
- Immunology
Background:
- Herpes simplex virus type 2 (HSV-2) intracerebral inoculation in mice leads to encephalitis and central nervous system demyelination.
- Ocular manifestations, such as pupillary light reflex impairment, are common sequelae in HSV-2 infected mice.
Purpose of the Study:
- To investigate the development and characteristics of ocular disease following intracerebral inoculation of HSV-2 (MS strain) in NIH mice.
- To determine the temporal progression of viral presence and pathological changes in ocular tissues.
Main Methods:
- Intracerebral inoculation of inbred NIH mice with a low dose (10 pfu) of HSV-2 (MS strain).
- Monitoring of encephalitis, pupillary light reflex, and mortality rates.
- Isolation of infectious virus, immunohistochemical detection of viral antigen, and electron microscopy in ocular tissues and nervous system.
- Histopathological examination of eyes, optic nerves, trigeminal ganglia, and brain.
Main Results:
- Acute encephalitis was fatal in 30-50% of mice; 80% of survivors showed impaired pupillary response by 1 month.
- Infectious HSV-2 was isolated from eyes by day 4 and viral antigen detected in optic nerves (day 5) and retinae (day 6).
- Necrotizing retinitis developed in up to half of mice during the second week, with high viral titers and antigen presence in the retina.
- Viral particles were confirmed in retinal glia and degenerating neurons via electron microscopy.
- Infectious virus persisted longer in eyes than in trigeminal ganglia or optic nerves, with titers declining to undetectable levels by 1 month.
Conclusions:
- Intracerebral HSV-2 infection in mice induces significant ocular pathology, including retinitis and visual reflex impairment.
- The eyes serve as a significant site for HSV-2 replication and persistence following central nervous system inoculation.
- Understanding the pathogenesis of HSV-2 ocular disease is crucial for developing effective therapeutic strategies.