Infectivity and Replication Inhibition Effect of 5-Fluorouracil on Herpes Simplex Virus Type-1 Associated With Mutations in Thymidine Kinase Gene

Abstract

Two pandemics over the first two decades of the 21st century have shown that viruses with epidemic and pandemic potentials constitute a major threat to human health due to the lack of effective antivirals. Developing new antivirals and treatment strategies is also as important as vaccines play a crucial role in the first line of preventing viral infections. Using base analogues that directly target viruses and understanding their action mechanisms can present essential alternative treatment strategies to combat viral diseases. The current study investigated the effects of a base analogue on herpes simplex virus type1 (HSV-1) replication in a cell culture system using the pyrimidine analogue 5-fluorouracil (FU). After that, the full-length UL-23 gene encoding thymidine kinase (TK) of HSV-1 was sequenced to detect induced mutations. The results showed a diminishing viral titre and viral load at 2 logs and 663 times, respectively, at the end of 10 consecutive passages with 5-FU. Furthermore, two mutations substitute amino acids in the non-conserved region of the TK gene, which confers drug resistance, were also identified. The current research is a feasibility study to investigate the antiviral effects of 5-FU on DNA viruses and has reinforced the fact that 5-FU can have an antiviral effect on HSV-1. However, drug resistance for viruses should not be underestimated.