Effect of pretreatment with toll-like receptor agonists in a mouse model of herpes simplex virus type 1 encephalitis.
BACKGROUND
We evaluated the effect of pretreatment with Toll-like receptor (TLR) agonists in a mouse model of herpes simplex virus type 1 (HSV-1) encephalitis.


METHODS
BALB/c mice received a single intraperitoneal or intranasal injection of polyinosinic:polycytidylic acid (poly I:C), a TLR3 agonist; lipopolysaccharide (LPS), a TLR4 agonist; oligodeoxynucleotide (ODN), a TLR9 agonist; or control vehicle. Twenty-four hours later, animals were infected with 5000 plaque-forming units of HSV-1.


RESULTS
Mice that received intraperitoneal pretreatment with vehicle, LPS, and poly I:C had survival rates of 7%, 13%, and 56%, respectively, and mean life expectancies of 156.80+/-9.56, 176.00+/-9.24, and 213.00+/-7.71 h, respectively (p< .05, poly I:C group vs. other groups). Similarly, intranasal pretreatment with vehicle, LPS, ODN, and poly I:C were associated with survival rates of 20%, 47%, 60%, and 94%, respectively, and mean life expectancies of 153.60+/-11.71, 188.80+/-12.97, 204.80+/-11.73, and 234.00+/-5.81 h, respectively (p< .05, ODN and poly I:C groups vs. vehicle group). Pretreatment with intranasal poly I:C induced early expression of several immune genes in the brain and resulted in a significantly lower virus load.


CONCLUSIONS
TLR3 stimulation by poly I:C 24 h before infection reinforces a natural innate immune mechanism of neuroprotection against HSV-1.
Boivin
Nicolas
N
Research Center in Infectious Diseases, CHUQ-CHUL, Quebec City, Canada. guy.boivin@crchul.ulaval.ca
Sergerie
Yan
Y
Rivest
Serge
S
Boivin
Guy
G
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D018792:Encephalitis, Viral / Q000188:drug therapy* / Q000517:prevention & control; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000821:virology; D009841:Oligonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000819:agonists*; D019562:Viral Load
D000998:Antiviral Agents; D008070:Lipopolysaccharides; D009841:Oligonucleotides; D051193:Toll-Like Receptors; D011070:Poly I-C