title: Toll-like receptor 7 suppresses virus replication in neurons but does not affect viral pathogenesis in a mouse model of Langat virus infection.
abstract: Toll-like receptor 7 (TLR7) recognizes guanidine-rich viral ssRNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs such as the central nervous system (CNS) is not as clear. This study examined the influence of TLR7 on the neurovirulence of Langat virus (LGTV), a ssRNA tick-borne flavivirus. TLR7 deficiency did not substantially alter the onset or incidence of LGTV-induced clinical disease; however, it did significantly affect virus levels in the CNS with a log(10) increase in virus titres in brain tissue from TLR7-deficient mice. This difference in virus load was also observed following intracranial inoculation, indicating a direct effect of TLR7 deficiency on regulating virus replication in the brain. LGTV-induced type I interferon responses in the CNS were not dependent on TLR7, being higher in TLR7-deficient mice compared with wild-type controls. In contrast, induction of pro-inflammatory cytokines including tumour necrosis factor, CCL3, CCL4 and CXCL13 were dependent on TLR7. Thus, although TLR7 is not essential in controlling LGTV pathogenesis, it is important in controlling virus infection in neurons in the CNS, possibly by regulating neuroinflammatory responses.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Baker
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA.
authors.forename: Tyson A
authors.initials: TA
authors.lastname: Woods
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA.
authors.forename: Niranjan B
authors.initials: NB
authors.lastname: Butchi
authors.affiliation: Department of Pathology, School of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Morgan
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA.
authors.forename: R Travis
authors.initials: RT
authors.lastname: Taylor
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Piyanate
authors.initials: P
authors.lastname: Sunyakumthorn
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA.
authors.forename: Piyali
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA.
authors.forename: Kirk J
authors.initials: KJ
authors.lastname: Lubick
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA.
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Best
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Peterson
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology* / Q000472:pathogenicity*; D004675:Encephalitis, Tick-Borne / Q000276:immunology / Q000473:pathology / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000821:virology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7