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Updated: Aug 11, 2026

Lentivirus-mediated Genetic Manipulation and Visualization of Olfactory Sensory Neurons in vivo
Published on: May 22, 2011
Herpes simplex encephalitis. Immunohistological demonstration of spread of virus via olfactory pathways in mice
Abstract:
Six-week-old Balb/c mice were inoculated intranasally with a suspension of HSV1 virus and the distribution of viral antigen in the brain 3-7 days later was surveyed using the immunoperoxidase technique. Virus was first detectable in the brain 4 days later at 2 distinct sites: the trigeminal root entry zone in the brain stem and the olfactory bulbs. On succeeding days virus spread from the trigeminal focus to many other brain stem nuclei and, in some mice, to the thalamus and the cerebellum. From the olfactory bulbs, in a proportion of mice, virus spread to anterior olfactory nucleus, lateral olfactory tract, septal nuclei, temporal lobe, hippocampus and cingulate cortex. Infection of olfactory bulbs was found to occur following intracorneal as well as intranasal inoculation of virus. The relevance of this model to human herpes simplex encephalitis is discussed.
Insights
Herpes Simplex Virus 1 (HSV1) infection in mice spreads from initial brain entry points, the trigeminal nerve and olfactory bulbs, to various brain regions. This mouse model aids understanding of HSV1 encephalitis.
Area of Science:
- Neurovirology
- Infectious Diseases
- Immunohistochemistry
Background:
- Herpes Simplex Virus 1 (HSV1) is a significant cause of encephalitis in humans.
- Understanding the initial sites and pathways of HSV1 neuroinvasion is crucial for developing effective treatments.
- Animal models are essential for studying viral pathogenesis and host responses.
Purpose of the Study:
- To investigate the early distribution and spread of HSV1 antigen within the mouse brain.
- To identify the primary sites of HSV1 entry and subsequent dissemination.
- To evaluate the utility of a mouse model for studying herpes simplex encephalitis.
Main Methods:
- Intranasal inoculation of six-week-old Balb/c mice with HSV1.
- Survey of viral antigen distribution in the brain using the immunoperoxidase technique.
- Observation period: 3-7 days post-inoculation.
Main Results:
- HSV1 was first detected in the brain at 4 days post-inoculation.
- Initial viral antigen was localized to the brain stem's trigeminal root entry zone and the olfactory bulbs.
- Subsequent viral spread occurred from the brain stem to other nuclei, thalamus, and cerebellum, and from olfactory bulbs to anterior olfactory nucleus, temporal lobe, hippocampus, and cingulate cortex.
Conclusions:
- The trigeminal nerve and olfactory bulbs serve as critical entry points for HSV1 into the mouse brain.
- HSV1 demonstrates distinct dissemination patterns from these initial sites, affecting various neural structures.
- This intranasal inoculation model effectively replicates key aspects of HSV1 neuroinvasion relevant to human herpes simplex encephalitis.

