Lack of interleukin-6 (IL-6) enhances susceptibility to infection but does not alter latency or reactivation of herpes simplex virus type 1 in IL-6 knockout mice.
The ability of the pleotropic, proinflammatory cytokine interleukin-6 (IL-6) to affect the replication, latency, and reactivation of herpes simplex virus type 1 (HSV-1) in cell culture and in IL-6 knockout (KO) mice was studied. In initial studies, we found no effect of exogenous IL-6, monoclonal antibodies to IL-6, or monoclonal antibody to the IL-6 coreceptor, gp130, on HSV-1 replication in vitro by plaque assay or reactivation ex vivo by explant cocultivation of latently infected murine trigeminal ganglia (TG). Compared with the wild-type (WT) mice, the IL-6 KO mice were less able to survive an ocular challenge with 10(5) PFU of HSV-1 (McKrae) (40% survival of WT and 7% survival KO mice; P = 0.01). There was a sixfold higher 50% lethal dose of HSV-1 in WT than IL-6 KO mice (1.7 x 10(4) and 2.7 x 10(3) PFU, respectively). No differences were observed in titers of virus recovered from the eyes, TG, or brains or in the rates of virus reactivation by explant cocultivation of TG from latently infected WT or KO mice. Exposure of latently infected mice to UV light resulted in comparable rates of reactivation and in the proportions of WT and KO animals experiencing reactivation. Moreover, quantitative PCR assays showed nearly identical numbers of HSV-1 genomes in latently infected WT and IL-6 KO mice. These studies indicate that while IL-6 plays a role in the protection of mice from lethal HSV infection, it does not substantively influence HSV replication, spread to the nervous system, establishment of latency, or reactivation.
LeBlanc
R A
RA
Medical Virology Section, Laboratory of Clinical Investigation, National Institutes of Health, Bethesda, Maryland 20892-1888, USA.
Pesnicak
L
L
Cabral
E S
ES
Godleski
M
M
Straus
S E
SE
D000818:Animals; D020022:Genetic Predisposition to Disease; D006561:Herpes Simplex / Q000235:genetics* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D014775:Virus Activation / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics*
D015850:Interleukin-6