title: Tick Saliva Enhances Powassan Virus Transmission to the Host, Influencing Its Dissemination and the Course of Disease.
abstract: Powassan virus (POWV) is an encephalitic tick-borne flavivirus which can result in serious neuroinvasive disease with up to a 10% case fatality rate. The study objective was to determine whether the salivary gland extract (SGE) from Ixodes scapularis ticks facilitates the transmission and dissemination of POWV in a process known as saliva-activated transmission. Groups of BALB/c mice were footpad inoculated with either a high dose of POWV with and without SGE or a low dose of POWV with and without SGE. Mice from each group were sacrificed daily. Organ viral loads and gene expression profiles were evaluated by quantitative real-time PCR. Both groups of mice infected with high-dose POWV showed severe neurological signs of disease preceding death. The presence of SGE did not affect POWV transmission or disease outcome for mice infected with the high dose of POWV. Neuroinvasion, paralysis, and death occurred for all mice infected with the low dose of POWV plus SGE; however, for mice infected with the low dose of POWV in the absence of SGE, there were no clinical signs of infection and no mice succumbed to disease. Although this group displayed low-level viremias, all mice were completely healthy, and it was the only group in which POWV was cleared from the lymph nodes. We conclude that saliva-activated transmission occurs in mice infected with a low dose of POWV. Our study is the first to demonstrate virus dose-dependent saliva-activated transmission, warranting further investigation of the specific salivary factors responsible for enhancing POWV transmission.
  
  
  OBJECTIVE
  Powassan virus (POWV) is a tick-borne flavivirus that continues to emerge in the United States, as is evident by the surge in number and expanding geographic range of confirmed cases in the past decade. This neuroinvasive virus is transmitted to humans by infected tick bites. Successful tick feeding is facilitated by a collection of pharmacologically active factors in tick saliva. In a process known as saliva-activated transmission, tick bioactive salivary molecules are thought to modulate the host environment, making it more favorable for the transmission and establishment of a pathogen. This phenomenon has been demonstrated for several tick-borne pathogens; however, a systematic investigation of the role of tick saliva on dissemination and pathogenesis of a tick-borne viral disease has never been attempted before. This study will fill that gap by systematically examining whether the presence of tick saliva contributes to the transmission and dissemination of POWV in mice.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Hermance
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA sathanga@utmb.edu.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Thangamani
mesh_terms: D000818:Animals; D001096:Arachnid Vectors / Q000821:virology*; D018450:Disease Progression; D004669:Encephalitis Viruses, Tick-Borne / Q000472:pathogenicity / Q000502:physiology*; D004675:Encephalitis, Tick-Borne / Q000401:mortality / Q000473:pathology / Q000635:transmission / Q000821:virology*; D005260:Female; D006801:Humans; D018884:Ixodes / Q000821:virology*; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012463:Saliva / Q000737:chemistry / Q000821:virology*; D014481:United States; D014774:Virulence