Tick-Borne Flaviviruses, with a Focus on Powassan Virus

Abstract

The tick-borne pathogen Powassan virus is a rare cause of encephalitis in North America and the Russian Far East. The number of documented cases described since the discovery of Powassan virus in 1958 may be <150, although detection of cases has increased over the past decade. In the United States, the incidence of Powassan virus infections expanded from the estimated 1 case per year prior to 2005 to 10 cases per year during the subsequent decade. The increased detection rate may be associated with several factors, including enhanced surveillance, the availability of improved laboratory diagnostic methods, the expansion of the vector population, and, perhaps, altered human activities that lead to more exposure. Nonetheless, it remains unclear whether Powassan virus is indeed an emerging threat or if enzootic cycles in nature remain more-or-less stable with periodic fluctuations of host and vector population sizes. Despite the low disease incidence, the approximately 10% to 15% case fatality rate of neuroinvasive Powassan virus infection and the temporary or prolonged sequelae in >50% of survivors make Powassan virus a medical concern requiring the attention of public health authorities and clinicians. The medical importance of Powassan virus justifies more research on developing specific and effective treatments and prevention and control measures.

Keywords: Powassan virus; arbovirus; viral encephalitis.

FIG 1

(A) Schematic representation of the flavivirus genome and translation of the viral polyprotein. (B) Proteolytic cleavage sites, individual proteins, and localization of nascent proteins in the endoplasmic reticulum. Scissors indicate viral (red) and cellular (green) proteases that are responsible for cleavage.

FIG 2

Geographic distribution of POWV. Dots indicate the locations where POWV was identified and/or serological assays provided indirect evidence for local circulation.

FIG 3

Epidemiological features of POWV infections between 2004 and 2016 in the United States. The panels show the annual number (A), the seasonal distribution (B), and the age distribution (C) of cases reported to the Centers for Disease Control and Prevention.

FIG 4

Phylogenetic tree showing the geographic distribution and species association of lineage I and II POWVs.

FIG 5

Enzootic cycles of lineage I and II POWVs linked to the main tick vector and some important vertebrate hosts. Humans are considered tangential hosts; arrows pointing to the silhouette on the right are indicative of the relative public health risk posed by different tick species (i.e., low risk for Ixodes marxi and Ixodes cookei and greater risk for Ixodes scapularis).

FIG 6

Clinical course and laboratory diagnosis of POWV infections. The timeline aligned with the phase of infection and typical clinical manifestations is shown in the top panel, whereas laboratory diagnostic opportunities relative to the timeline of clinical disease are shown in the middle and bottom panels.