Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations
This article has been cited by other articles in PMC. Latency-associated transcript has several known functions and may contain additional functions that are important for the latency– reactivation cycle. Positive-sense single-stranded (ss) RNA viruses (+ssRNA; RNA phage Qβ, poliovirus10 and Tobacco mosaic virus103), negative-sense ssRNA viruses (-ssRNA; vesicular stomatitis virus, influenza A virus10 and measles virus23), the retrotranscribing viruses (Retro; spleen necrosis virus, murine leukaemia virus, Rous sarcoma virus10, human immunodeficiency virus type-1 and bovine leukaemia virus2) and the double-stranded (ds) RNA virus (dsRNA; bacteriophage φ6 (Ref. We have examined mutational events at TC/AG microsatellites, the second most abundant dinucleotide repetitive motif in the human genome. Fanconi’s anaemia (FA) cells are hypersensitive to the lethal effect of DNA cross-linking compounds. Viruses are simple entities, lacking an energy-generating system and having very limited biosynthetic capabilities. Double-stranded (ds) DNA viruses are often described as evolving through long-term codivergent associations with their hosts, a pattern that is expected to be associated with low rates of nucleotide substitution.
Herpes simplex virus (HSV) entry into cells is triggered by the binding of envelope glycoprotein D (gD) to a specific receptor, such as nectin-1 or herpesvirus entry mediator (HVEM), resulting in activation of the fusion effectors gB and gH and virus penetration. Rates of spontaneous mutation have been estimated under optimal growth conditions for a variety of DNA-based microbes, including viruses, bacteria, and eukaryotes. Rates of spontaneous mutation determine the ability of viruses to evolve, infect new hosts, evade immunity and undergo drug resistance. Tumor suppressor gene inactivation is a crucial event in oncogenesis. We have measured the spontaneous production of mutants in derivatives of herpes simplex virus type 1 resistant to phosphonoacetic acid. In fact, wild type HSV-1 and the antimutator HSV-1 PAAr5 exhibited a 2–4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Msh2, Msh3, and Msh6 are mammalian homologues of the bacterial DNA mismatch repair (DMR) mutS gene involved in the repair of base pair mismatches and insertion-deletion (I/D) heterologies (15).
NASA is currently working with the University of Florida to investigate why at least four strains of the herpes virus (including the zoster variation) reactivate due to space travel. Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. We have previously described the use of homologous recombination and CRE-loxP-mediated marker recycling to generate mouse embryonic stem (ES) cell lines homozygous for mutations at theMsh3, Msh2, and both Msh3 andMsh2 loci (2). While large DNA viruses are thought to have low mutation rates, only a small fraction of their genomes have been analyzed at the single-nucleotide level. Genome-wide demethylation has been suggested to be a step in carcinogenesis. Rates of spontaneous mutation determine the ability of viruses to evolve, infect new hosts, evade immunity and undergo drug resistance. The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations.
HSV-1, on the other hand, can in rare cases cause blindness, encephalitis, and even death. The processivity subunit of the herpes simplex virus DNA polymerase, UL42, is essential for viral replication and possesses both Pol- and DNA-binding activities. Fortunately, scientists today genetic tools such as the use of DNA sequencing to new strains of virus to learn. The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) gene is essential for efficient spontaneous reactivation of HSV-1 from latency. Previous reports have suggested that herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP0 stabilizes cyclins D1 and D3 during infection by inducing the degradation of cdc34, the E2-conjugating enzyme that is responsible for regulating the stability of these cyclins. Kosakovsky Pond SL, Frost SD (2005) Not So Different After All: A Comparison of Methods for Detecting Amino Acid Sites Under Selection. We have previously described the use of homologous recombination and CRE-loxP-mediated marker recycling to generate mouse embryonic stem (ES) cell lines homozygous for mutations at the Msh3, Msh2, and both Msh3 and Msh2 loci (2).