Gamma interferon can prevent herpes simplex virus type 1 reactivation from latency in sensory neurons

T Liu, KM Khanna, BN Carriere… - Journal of virology, 2001 - Am Soc Microbiol
T Liu, KM Khanna, BN Carriere, RL Hendricks
Journal of virology, 2001Am Soc Microbiol
We recently demonstrated that CD8+ T cells could block herpes simplex virus type 1 (HSV-
1) reactivation from latency in ex vivo trigeminal ganglion (TG) cultures without destroying
the infected neurons. Here we establish that CD8+ T-cell prevention of HSV-1 reactivation
from latency is mediated at least in part by gamma interferon (IFN-γ). We demonstrate that
IFN-γ was produced in ex vivo cultures of dissociated latently infected TG by CD8+ T cells
that were present in the TG at the time of excision. Depletion of CD8+ T cells or …
Abstract
We recently demonstrated that CD8+ T cells could block herpes simplex virus type 1 (HSV-1) reactivation from latency in ex vivo trigeminal ganglion (TG) cultures without destroying the infected neurons. Here we establish that CD8+ T-cell prevention of HSV-1 reactivation from latency is mediated at least in part by gamma interferon (IFN-γ). We demonstrate that IFN-γ was produced in ex vivo cultures of dissociated latently infected TG by CD8+ T cells that were present in the TG at the time of excision. Depletion of CD8+ T cells or neutralization of IFN-γ significantly enhanced the rate of HSV-1 reactivation from latency in TG cultures. When TG cultures were treated with acyclovir for 4 days to insure uniform latency, supplementation with recombinant IFN-γ blocked HSV-1 reactivation in 80% of cultures when endogenous CD8+ T cells were present and significantly reduced and delayed HSV-1 reactivation when CD8+ T cells or CD45+ cells were depleted from the TG cultures. The effectiveness of recombinant IFN-γ in blocking HSV-1 reactivation was lost when its addition to TG cultures was delayed by more than 24 h after acyclovir removal. We propose that when the intrinsic ability of neurons to inhibit HSV-1 gene expression is compromised, HSV-specific CD8+ T cells are rapidly mobilized to produce IFN-γ and perhaps other antiviral cytokines that block the viral replication cycle and maintain the viral genome in a latent state.
American Society for Microbiology