Characterization of latent infections in mice inoculated with herpes simplex virus which is clinically resistant to...

Area of Science:

• Virology
• Immunology
• Neuroscience

Background:

• Herpes simplex virus (HSV) establishes lifelong latent infections, primarily in sensory neurons.
• Acyclovir (ACV) is a primary antiviral agent for HSV, targeting viral thymidine kinase (TK).
• TK-deficient (TK-) HSV strains are intrinsically resistant to ACV chemotherapy.

Purpose of the Study:

• To investigate the impact of ACV chemotherapy on the establishment and maintenance of latent HSV infections, particularly involving TK- virions.
• To characterize the properties of latent TK- HSV recovered from infected mice.

Main Methods:

• Mice were inoculated with an HSV-1 strain containing both TK+ and TK- virions, resistant to ACV.
• Suboptimal ACV chemotherapy was administered during the acute infection phase.
• Cervical dorsal root ganglia were explanted and cultured in vitro to detect latent HSV reactivation.
• Reactivated viral isolates were characterized for TK activity and virulence.

Main Results:

• ACV chemotherapy during acute infection did not prevent the establishment of latent HSV infections.
• Both TK+ and TK- HSV were recovered from explanted ganglia, indicating successful latency of both viral types.
• A TK- HSV isolate from ganglia was found to be attenuated in vitro.
• The establishment of latency was unaffected by the presence of ACV-resistant TK- virions.

Conclusions:

• Acyclovir chemotherapy is ineffective in preventing the establishment of latent herpes simplex virus infections, even when resistant TK- strains are present.
• Latent infections can be established by both ACV-sensitive (TK+) and ACV-resistant (TK-) HSV strains.
• TK- HSV strains recovered from latent infections may exhibit attenuated virulence, similar to in vitro-selected strains.