Translational research in Tick-Borne Encephalitis (TBE) and other flavivirus infections

My research is centered on translational and clinical virology, with a particular focus on flavivirus infections, host–virus interactions, biomarkers of disease and treatment outcome, antiviral mechanisms, and the translation of laboratory findings into clinical applications.

A major focus of my earlier research was hepatitis C virus (HCV), a virus distantly related to tick-borne encephalitis virus (TBEV) and West Nile virus (WNV). My work contributed to the identification and characterization of host factors influencing the outcome of antiviral therapy for HCV. In particular, we established the prognostic significance of pretreatment serum concentrations of interferon gamma-induced protein 10 (IP-10/CXCL10) and genetic variation in the interferon lambda 4 gene (IFNL4, initially designated IL28B) for predicting response to interferon- and ribavirin-based treatment. We also demonstrated that IFNL4 variants associated with the ability to produce interferon lambda 4 influence antibody responses to HCV.

Another important area of my research has been the mechanism of action and toxicity of ribavirin. Our studies demonstrated that genetic variants in the ITP pyrophosphatase gene (ITPA) modulate the metabolism of ribavirin triphosphate, providing mechanistic insight into interindividual differences in ribavirin-associated effects. This laboratory-based work was complemented by extensive involvement in investigator-initiated and multicenter clinical trials of HCV therapy, including the RibaC, NORDynamIC, RelapC, and EU-sponsored DITTO-HCV trials.

More recently, my research has shifted toward tick-borne encephalitis (TBE), an emerging flavivirus infection of the central nervous system that represents a growing public health challenge in Sweden and elsewhere in Europe. TBE may result in severe and persistent neurological sequelae, yet reliable biomarkers predicting progression and clinical outcome remain lacking. Although effective vaccines are available, breakthrough infections occur and may occasionally be severe or fatal. TBE can also have devastating consequences in immunocompromised patients, including transplant recipients. Importantly, there is currently no licensed antiviral treatment for TBE.

My current research addresses these unmet needs through complementary diagnostic, immunological, antiviral, and clinical approaches. We have demonstrated that remdesivir has potent in vitro antiviral activity against TBEV through specific inhibition of the viral RNA-dependent RNA polymerase. The emergence of resistance-associated double substitutions in the viral NS5 protein provided further evidence for this mechanism and established a rationale for evaluating remdesivir as potential treatments for severe TBE.

In parallel, we are developing a rapid cytokine-release T-cell assay for TBEV as a complement to currently available whole-virus and non-structural protein 1 (NS1)-based serological assays. The aim is to improve characterization of TBEV-specific immunity, particularly the ability to distinguish vaccine-induced from infection-induced immune responses and to identify breakthrough infections despite prior vaccination. This work may also provide new tools for studying immune responses in relation to disease severity and clinical outcome.

A further major objective is to translate these laboratory findings into clinical intervention. I am contributing to the development of a Swedish multicenter network comprising university hospitals and clinical centers treating patients with TBE. The long-term goal is to establish the infrastructure required for randomized clinical trials evaluating antiviral therapy for TBE. Within this network, we aim to establish our laboratory as a central research laboratory, coordinating virological and immunological assays and facilitating harmonized sample collection and translational studies across participating centers.

Taken together, my research represents a progression from mechanistic and clinical studies of HCV toward a broader translational research program in flavivirus infections, with TBE as the current principal focus. By integrating clinical virology, antiviral pharmacology, host immune responses, biomarker development, and multicenter clinical trials, the overarching goal is to improve the diagnosis, prognostication, and ultimately treatment of patients with TBE and other medically important flavivirus infections.