Combined use of pritelivir with acyclovir or foscarnet suppresses evolution of HSV-1 drug resistance.

The widespread use of antivirals in immunocompromised individuals has led to frequent occurrences of drug-resistant herpes simplex virus 1 (HSV-1) infections. Current antivirals target the viral DNA polymerase (DP), resulting in cross-resistance patterns that emphasize the need for novel treatment strategies. In this study, we assessed whether combining antivirals with different targets affects drug resistance emergence by passaging wild-type HSV-1 under increasing concentrations of acyclovir (ACV), foscarnet (phosphonoformic acid, PFA), or the helicase-primase inhibitor pritelivir (PTV), individually or in combination (ACV + PTV or PFA + PTV).

Dynamics and Evolution of Donor-derived Cytomegalovirus Infection in 3 Solid Organ Transplant Recipients With the Same Multiorgan Donor.

Background: Cytomegalovirus (CMV) infection poses a significant risk to immunosuppressed transplant recipients, manifesting through primary infection, reinfection, or reactivation.

Methods: We analyzed the emergence of drug resistance in CMV infection in 3 patients who were later found to have received an allograft from a shared, deceased donor. The seronegative transplant recipients developed symptomatic CMV infections after bowel/pancreas, kidney, or lung transplantation.

CRISPR/Cas9-mediated genome editing of the thymidine kinase gene in a clinical HSV-1 isolate identifies F289S as novel acyclovir-resistant mutation.

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that establishes a lifelong infection in sensory neurons of infected individuals, accompanied with intermittent reactivation of latent virus causing (a)symptomatic virus shedding. Whereas acyclovir (ACV) is a safe and highly effective antiviral to treat HSV-1 infections, long-term usage can lead to emergence of ACV resistant (ACV) HSV-1 and subsequently ACV refractory disease. Here, we isolated an HSV-1 strain from a patient with reactivated herpetic eye disease that did not respond to ACV treatment.