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Targets of herpes simplex virus type 1 infection in a mouse corneal model
J R Martin1, F J Jenkins, D B Henken
1Laboratory of Experimental Neuropathology, NINDS, NIH, Bethesda, MD 20892.
Abstract:
In animal models, spread of herpes simplex virus type 1 (HSV-1) from epithelial replication sites to the peripheral and central nervous system is known from analysis of individually dissected tissues. To examine virus spread in undissociated tissues, corneas of adult mice were inoculated with HSV-1. After 1 to 13 days groups of mice were perfused with formalin, and decalcified blocks of head and neck were embedded in paraffin. At intervals, serial sections were screened for HSV antigen. On days 1 and 2, viral antigen was restricted to cornea and conjunctiva but by days 3 and 4 was also seen in autonomic ganglia and the trigeminal system. On day 6, HSV antigen reached its maximum extent; infected sites included the trigeminal complex (ganglion, root, peripheral ophthalmic and maxillary branches and spinal nucleus and tract), ethmoid sinus and olfactory bulb, visual system, and autonomic ganglia (ciliary, pterygopalatine and superior cervical). Antigen progressively diminished on days 8 and 10, and was not detected on day 13. This method demonstrates a broader range of infected tissues and suggests a more complex pattern of HSV spread than has been previously recognized. Virus appears to reach the intracranial compartment by four different neural routes. When effects of higher and lower corneal inoculation doses were compared, a lower dose resulted in lower peak HSV titers in trigeminal ganglion and brain stem and later virus appearance in these tissues. Thus, dose may influence the kinetics of HSV spread from the peripheral inoculation site to the CNS.
Insights
Herpes simplex virus type 1 (HSV-1) spreads through undissociated mouse tissues, reaching the central nervous system via multiple neural routes. Lower initial doses reduced viral spread and delayed CNS infection.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Herpes simplex virus type 1 (HSV-1) neuroinvasion is typically studied in dissected tissues.
- Understanding HSV-1 spread in intact tissues is crucial for comprehending pathogenesis.
Purpose of the Study:
- To investigate HSV-1 spread within undissociated head and neck tissues in a mouse model.
- To identify the neural pathways involved in HSV-1 central nervous system (CNS) entry.
- To evaluate the impact of inoculation dose on viral kinetics.
Main Methods:
- Corneal inoculation of adult mice with HSV-1.
- Serial sectioning and HSV antigen screening of perfused and embedded head and neck tissues from day 1 to 13 post-inoculation.
- Comparison of high and low corneal inoculation doses.
Main Results:
- HSV-1 antigen was detected in the cornea and conjunctiva by days 1-2.
- Viral spread to the trigeminal system and autonomic ganglia occurred by days 3-4.
- Maximum viral antigen extent was observed on day 6, including the trigeminal complex, olfactory bulb, and visual system.
- HSV-1 reached the intracranial compartment via four distinct neural routes.
- Lower inoculation doses led to reduced peak viral titers and delayed CNS infection.
Conclusions:
- The study reveals a more extensive and complex pattern of HSV-1 spread in intact tissues than previously recognized.
- Multiple neural pathways facilitate HSV-1 entry into the CNS.
- The inoculation dose significantly influences the kinetics of HSV-1 neuroinvasion.