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Heterotypic and homotypic re-inoculation of mice already latently infected with herpes simplex virus type 1
D L Yirrell1, W A Blyth, T J Hill
1Department of Microbiology, School of Medical Sciences University of Bristol, England.
Abstract:
Mice were infected at 4 weeks of age with a type 1 strain of herpes simplex virus (HSV) and re-infected 4 weeks later with either a type 1 or a type 2 strain of HSV. The virus used for first infection could be distinguished from that used later since it was resistant to phosphonoformic acid and formed syncytial plaques. Sites used for the second inoculation were as follows: at the site of primary infection, at a different site within the same dermatome or in the equivalent dermatome on the opposite side (also called "remote" site). Re-infection caused no detectable reactivation of the latent PFA resistant virus. After re-infection with a homotypic virus replication of the re-infecting virus was limited to the inoculation site. However after heterotypic re-infection the type 2 strain was occasionally isolated from the ganglia. Previous infection with the PFA resistant type 1 strain clearly reduced the ability of the homotypic or heterotypic strains to establish a latent infection. However, in a few animals ganglia were found to be latently infected with virus from both the first and second inoculations. Analysis of the results suggests that resistance to the establishment of a second latent infection in a ganglion is determined by the general immunity of the animal rather than "immunity" of the latently infected ganglion itself.
Insights
Previous herpes simplex virus (HSV) infection in mice reduced the ability of subsequent HSV strains to establish a latent infection. General animal immunity, not ganglion-specific immunity, appears to determine resistance to a second latent HSV infection.
Area of Science:
- Virology
- Immunology
Background:
- Herpes simplex virus (HSV) establishes lifelong latent infections.
- Understanding factors influencing secondary latent infections is crucial for managing HSV recurrence.
Purpose of the Study:
- To investigate the impact of a primary HSV-1 infection on the establishment of a secondary latent infection by homologous (HSV-1) or heterologous (HSV-2) strains.
- To determine whether prior infection confers resistance to superinfection in the nervous system.
Main Methods:
- Mice were infected with a phosphonoformic acid (PFA)-resistant HSV-1 strain.
- Re-infection occurred 4 weeks later with either HSV-1 or HSV-2 at various sites (primary site, same dermatome, contralateral dermatome).
- Viral latency and reactivation were assessed through isolation from inoculation sites and ganglia.
Main Results:
- Re-infection did not reactivate the latent primary PFA-resistant HSV-1.
- Homotypic re-infection (HSV-1) was limited to the inoculation site.
- Heterotypic re-infection (HSV-2) occasionally led to latent infection in ganglia.
- Primary HSV-1 infection significantly reduced the establishment of secondary latent infections.
Conclusions:
- Prior HSV infection confers resistance to a second latent infection.
- This resistance is likely mediated by systemic immunity rather than localized immunity within the infected ganglion.
- Co-infection with both homologous and heterologous strains was observed in a small number of animals.