Ganglionic permissivity to HSV-1 replication and acyclovir-induced latency: an in vitro model.
HSV-1 is known to establish latent infections in murine trigeminal ganglia. In order to study the genetic influence of the host on permissivity to HSV-1 replication and latency in mouse trigeminal ganglia, an in vitro culture system was developed. Ganglia from HSV sensitive A/J and resistant C57BL/6J mice were harvested and inoculated in vitro with either MP or KOS strains of HSV-1. Infected ganglia were placed in culture for 7 days with or without 150 micrograms/ml acyclovir. Ganglia were then homogenized and assayed for infectious particles or frozen whole for standard immunostaining. A/J ganglia without acyclovir consistently demonstrated a three-fold higher viral replication compared to C57BL/6J ganglia without acyclovir for both MP and KOS. Indirect immunofluorescent staining of actively infected ganglia using rabbit anti-HSV antiserum showed increased staining in A/J ganglionic axons compared to C57BL/6J ganglionic axons. Ganglia from both murine strains showed total suppression of viral replication with acyclovir treatment. Immunostaining for latent viral protein with mouse monoclonal anti-ICP-4 (VP 175) was positive for both A/J and C57BL/6J strains following acyclovir treatment. Desuppression of acyclovir-treated whole ganglia resulted in 54% spontaneous HSV reactivation. These results suggest that: (1) HSV-1 can establish an active infection in whole murine trigeminal ganglia in vitro; (2) HSV-1 replicates to a greater extent in A/J ganglia compared to C57BL/6 ganglia; and (3) in vitro HSV-1 ganglionic infection in both murine strains is equally suppressed to a latent state by acyclovir treatment.
Millin
J A
JA
Hilles Immunology Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston 02114.
Opremcak
E M
EM
Wells
P A
PA
Foster
C S
CS
D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D005724:Ganglia / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology*; D014276:Trigeminal Nerve / Q000382:microbiology; D014775:Virus Activation / Q000187:drug effects*; D014779:Virus Replication
D000212:Acyclovir