Challenges and opportunities in the management of herpesvirus antiviral-resistance

Human herpesviruses are prevalent pathogens usually causing insignificant disease in healthy persons. However, primary infection or reactivation with one of the eight human herpesviruses can result in severe disease in patients with an impaired immune system. Major advances have been made in the management of herpesvirus infections among immunocompromised patients. Yet, these patients often require prolonged antiviral therapy increasing the risks for selection of drugresistant viruses. In contrast to HIV, there are no well-established algorithms for monitoring and treating herpesvirus drug-resistance and clinically unresponsive herpesvirus infections are generally treated empirically without analyzing the virus resistance profile. Furthermore, several issues such as viral heterogeneity, evolution of viral subpopulations, viral compartmentalization, replication capacity and pathogenicity of mutant viruses are poorly understood in herpesviruses. Our research focuses on investigating herpesvirus dynamics, diversity, and the mechanisms of viralinduced pathology in order to establish guidelines for management of herpesvirus infections. These studies will help introducing ‘tailored’ medicines that will replace the current ‘one-size-fits-all’ view of anti-herpesvirus therapy.