Innate Immune Response to Powassan Virus Infection: Progress Toward Infection Control

Abstract

Powassan virus is an emerging tick-borne flavivirus that poses a significant threat to human health. The outcome of Powassan virus infection is shaped by both viral factors and the host immune response. While this review aimed to examine the innate immune response, particularly toll-like receptor-mediated immune responses to Powassan virus, data specific to the immune response to Powassan virus remain scarce. Therefore, we focused on toll-like receptor responses to related flaviviruses to infer possible mechanisms of host response. Insights from both in vivo and in vitro studies are critical for guiding the development of effective therapeutic and preventive strategies. Currently, there are no clinically approved treatments or vaccines for Powassan virus, highlighting the urgent need for their development. We also highlight recent progress in POWV vaccine development, with an emphasis on the potential use of toll-like receptor agonists as adjuvants to enhance immunogenicity and improve vaccine efficacy.

Keywords: Powassan virus; adjuvants; immune response; toll-like receptor; toll-like receptor agonist; vaccine.

Figure 1

A simplified schematic presentation of TLR response to flavivirus infection. TLR signaling is activated upon detection of the viral proteins or nucleic acids, which culminates in the induction of proinflammatory cytokines, interferon-stimulated genes (ISGs) and interferons. MyD88 (myeloid differentiation primary response 88), TIRAP (toll-interleukin 1 receptor domain–containing adaptor protein), TRIF (TIR domain–containing adaptor–inducing IFN-β), IRAK1 (interleukin-1 receptor-associated kinase 1), IRAK4 (interleukin-1 receptor-associated kinase 4), TRAF3 (TNF receptor–associated factor 3), TRAF6 (TNF receptor-associated factor 6), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), IRF3 (interferon regulatory factor 3), IRF7 (interferon regulatory factor 7), IFN (interferon), POWV (Powassan virus).