Lethal Mutagenesis in Viruses and Its Effects

Abstract

 Viruses are biological systems with wide variations in mutation rates. Viruses with highly accurate and conforming transcriptases have relatively low mutation rates. In contrast, viruses with high aberration transcriptases show high mutation rates, and high mutation rates can lead to higher genetic diversity. Viruses cannot be increased further without sacrificing by viral consistency according to the adaptive landscapes. A mutation can be defined as permanent changes that occur in the nucleotide sequence or the structure of nucleotides, often resulting in genetic material changes and structural disruption, thus, affect the polypeptide synthesis. Mutations can be created spontaneously or by physical-chemical properties. The nucleic acid mutations in viruses also determine their genome characteristics. Lethal mutagenesis is a broad-spectrum antiviral strategy that takes advantage of the high mutation rate and low mutation tolerance of many RNA viruses. Mutagenic drugs employ this strategy to increase the mutation rate of the virus, thus, leading a large number of mutations in the viral population, either lethal or highly harmful for continuesity of replication. Such an example Acyclovir (ACV), which is used for effective treatment in herpes simplex virus infections, works by blocking the thymidine kinase enzyme of the virus, only by entering the virus-infected cells. however, the virus developed resistance to this mechanism by generating mutant strains lacking thymidine kinase enzyme. In determining virus mutations, comparison with wild type is made phenotypically, but since it is very difficult to make this comparison in a genome that is found to be mutated frequently, making viral genome sequences has become a more effective method.