Herpesvirus delivery to the murine respiratory tract

Cindy S E Tan1, Bruno Frederico2, Philip G Stevenson3

  • 1Sir Albert Sakzewski Virus Research Centre, Queensland Children's Medical Research Institute and Australian Infectious Disease Research Centre, University of Queensland and Royal Children's Hospital, Brisbane, Queensland 4029, Australia.

Insights

Understanding herpesvirus host entry is crucial. This study shows that intranasal delivery in mice effectively models natural herpesvirus infection, highlighting the nasal route for initial host entry.

Area of Science:

  • Virology
  • Infectious Diseases
  • Animal Models

Background:

  • Herpesvirus transmission and host entry mechanisms are poorly understood due to sporadic infections and artificial experimental models.
  • Mice are commonly used to study viral infections, but validating experimental inoculation methods for natural routes of infection is essential.

Purpose of the Study:

  • To investigate the natural route of herpesvirus host entry using a refined experimental model in mice.
  • To validate low-volume intranasal inoculation as a physiologically relevant method for modeling herpesvirus upper respiratory tract infections.

Main Methods:

  • Alert mice were intranasally inoculated with small liquid volumes (1-5 μl) containing markers (Indian ink, luciferase, radiolabel) or viruses (Murid Herpesvirus-4, Herpes simplex virus type 1).
  • Tracking experiments monitored inoculum distribution, and infection sites were analyzed.
  • Comparison was made with larger inoculum volumes (30 μl) and anesthesia-assisted delivery.

Main Results:

  • Intranasal inoculation of small volumes in alert mice primarily infected the nasal cavity, suggesting nasal entry.
  • Virus delivered via larger volumes or with anesthesia led to lung infection, but this method requires further validation for physiological relevance.
  • Tracking revealed that even small nasal inocula predominantly distribute to the oropharynx, indicating limited liquid retention in the nasal cavity.

Conclusions:

  • Low-volume intranasal delivery to alert mice provides a convenient and potentially natural route for experimental herpesvirus host entry modeling.
  • The nasal cavity appears to be a primary site for initial herpesvirus host entry, despite challenges with liquid retention.
  • Further research is needed to fully validate the physiological relevance of experimental infection models for herpesviruses.

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