Severity of experimentally reactivated herpetic eye disease is related to the neurovirulence of the latent virus.
The authors examined the eye diseases produced during acute and experimentally reactivated infections of rabbits intranasally inoculated with high and low neurovirulent strains of herpes simplex virus, type-1 (HSV-1). Experimental reactivation of latent trigeminal ganglionic infection was accomplished by an injection of cyclophosphamide followed by one injection of dexamethasone the next day. Neither drug, when given as a single injection, reactivated latent HSV-1 infection. During acute and reactivated phases of high neurovirulent HSV-1 strain infection, many rabbits developed very severe conjunctivitis and keratitis. Some rabbits developed hemorrhagic corneal lesions, and a few became blind. Only a few rabbits with acute and reactivated low neurovirulent virus strain infections developed mild conjunctivitis. The high neurovirulent strain was recovered from tear film more frequently than the low neurovirulent strain during reactivated infections. By use of 3H-labelled DNA prepared from purified virus to probe trigeminal ganglionic tissues in situ, both strains of virus were found to establish ganglionic latency to about the same degree. Reactivation correlated with an increase in the amount of HSV-1 RNA per ganglionic neuron and a change in subcellular location. These studies indicate that the relative neurovirulence of the infecting strain determines the ease with which it can be reactivated from latency and the severity of the reactivated ocular disease produced.
Stroop
W G
WG
Neurovirology Research Laboratory, VA Medical Center, Salt Lake City, UT 84148, USA.
Schaefer
D C
DC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003236:Conjunctivitis, Viral / Q000209:etiology* / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D018259:Herpesvirus 1, Human / Q000472:pathogenicity / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016849:Keratitis, Herpetic / Q000209:etiology* / Q000473:pathology; D009297:Nasal Mucosa / Q000821:virology; D011817:Rabbits; D013666:Tears / Q000821:virology; D012668:Trigeminal Ganglion / Q000473:pathology / Q000821:virology*; D014774:Virulence; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000502:physiology*; D017201:Virus Shedding
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D003520:Cyclophosphamide