Of Murines and Humans: Modeling Persistent Powassan Disease in C57BL/6 Mice
Feb. 21, 2021
Powassan infection is caused by two closely related, tick-transmitted viruses of the genus Flavivirus (family Flaviviridae): Powassan virus lineage I (POWV) and lineage II (known as deer tick virus [DTV]). Infection is typically asymptomatic or mild but can progress to neuroinvasive disease. Approximately 10% of neuroinvasive cases are fatal, and half of the survivors experience long-term neurological sequelae. Understanding how these viruses cause long-term symptoms as well as the possible role of viral persistence is important for developing therapies.
We intraperitoneally inoculated 6-week-old C57BL/6 mice (50% female) with 103 focus-forming units (FFU) DTV and assayed for infectious virus, viral RNA, and inflammation during acute infection and 21, 56, and 84 days postinfection (dpi). Although most mice (86%) were viremic 3 dpi, only 21% of the mice were symptomatic and 83% recovered. Infectious virus was detected only in the brains of mice sampled during the acute infection. Viral RNA was detected in the brain until 84 dpi, but the magnitude decreased over time. Meningitis and encephalitis were visible in acute mice and from mice sampled at 21 dpi. Inflammation was observed until 56 dpi in the brain and 84 dpi in the spinal cord, albeit at low levels.
These results suggest that the long-term neurological symptoms associated with Powassan disease are likely caused by lingering viral RNA and chronic inflammation in the central nervous system rather than by a persistent, active viral infection. The C57BL/6 model of persistent Powassan mimics illness in humans and can be used to study the mechanisms of chronic disease.
- Powassan is NOT rare:
For the last two years, Coppe Laboratories has dedicated a significant amount of time and resources to dispelling the myth that infection with Powassan virus, a virus transmitted by tick bite, is rare. The Centers for Disease Prevention and Control (CDC) reports only 100 cases of Powassan virus infection in the United States in the last 10 years. Indeed, that statistic gives the illusion that Powassan infection is rare. However, did you know that the only infections reported to CDC are those that are life-threatening, particularly cases causing severe inflammation of the brain like the case reported in LiveScience? Coppe has published three new papers in the last year that clearly show Powassan virus infection is not rare are at all, and until testing for this virus is included as part of tick-borne disease screening panels infections will continue to be underreported. Coppe’s Powassan Guide, which can be downloaded from the website, summarizes the findings from both tick and human Powassan prevalence studies, as well as defining the patient populations that would benefit most from Powassan testing.