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Updated: Apr 28, 2026

Measurement of γHV68 Infection in Mice
Published on: November 22, 2011
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.
Abstract:
Herpesvirus transmission is sporadic, and infection may be asymptomatic or present only with secondary lesions after dissemination. Consequently host entry remains ill-understood. Experimental infections can be informative, but depend on inoculations that are inherently artificial and so need validation. Mice are a widely used experimental host. Alert mice inhale readily small (5 μl) liquid volumes, and Indian ink, luciferase or radiolabel delivered thus distributed to the nasopharynx and oropharynx. Murid Herpesvirus-4 or Herpes simplex virus type 1 delivered thus infected only the nose, arguing that host entry is nasal rather than oral. Marker or virus delivery to the lung depended on general anesthesia and a large inoculum volume (30 μl), and so needs further validation of physiological relevance. While lungs could be infected at lower doses than the upper respiratory tract, tracking experiments showed that nasal inocula pass mostly into the oropharynx, even when restricted to 1 μl. Thus, the relative inefficiency of experimental upper respiratory tract infection was attributable to limited liquid retention in this site. Nonetheless low volume intranasal delivery to alert mice provides a convenient way to model experimentally an apparently natural mode of herpesvirus host entry.
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.

