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The replicative polymerase of herpes simplex virus (HSV) is comprised of catalytic (Pol) and processivity subunits (UL42) [9,11]. Neonatal herpes and the associated problems of diagnosis and perinatal transmission have been discussed at length elsewhere (106). This is the first report to our knowledge of the mutation rates at TC/AG microsatellite alleles in eukaryotic or prokaryotic cells. The error rate for DNA viruses has been calculated to be 10-8 to 10-11 errors per incorporated nucleotide. Recently, a concerted effort has been made to unravel the phylogenetic and demographic contexts that have led to this diversity of relationships (Pérez-Losada et al. Full text Full text is available as a scanned copy of the original print version. These DNA lesions arise in the genome through a number of mechanisms, including replication errors and recombination between diverged sequences (homeologous recombination) (16).

Bacteria multiply through cell division. Receptor binding disrupts this engagement and liberates the effector domain to activate gB and/or gH/gL. Spontaneous mutations are key drivers of evolution and disease. Next-generation sequencing has provided a powerful tool for studying microbial genetic diversity but suffers from relatively low per-base accuracy, limiting our ability to detect low-frequency polymorphisms and spontaneous mutations. Surprisingly, the fraction of CpG transition mutations was not reduced in Dnmt1-deficient cells. Entry of the gB mutant virus into nectin-1-bearing cells was markedly accelerated compared to that of wild-type virus, suggesting that the gB mutations affect a rate-limiting step in entry. Mutations in Msh2, Msh6, and Msh3 also result in instability of the size of simple sequence repeats or microsatellites (24, 26, 37, 41).

Theory posits a direct relationship between these two processes, but this has rarely been tested empirically. Returned for modification 19 June 1999. Mutants emerge after passage through mice lacking adaptive immunity but carrying the Cmv1r allele, which encodes the Ly49H activation receptor on NK cells (7, 19). Next-generation sequencing has provided a powerful tool for studying microbial genetic diversity but suffers from relatively low per-base accuracy, limiting our ability to detect low-frequency polymorphisms and spontaneous mutations. When rates of spontaneous mutation are expressed per genome per genome replication, different broad groups of organisms display characteristic values (3): roughly 0.2 for retroelements; close to 0.0034 for DNA-based microbes (including both viral and cellular organisms); and roughly 0.01 for higher eukaryotes. However, HSV-2 strains may have a greater propensity to generate drug-resistant mutants than do HSV-1 strains. Thus, a processivity factor can influence replication fidelity in mammalian cells.

When the virus makes a mistake in copying DNA, the host cell can often correct the error. This was unexpected, since LAT null mutants and LAT3.3A have wild-type virulence. The presence of active ICP0 greatly increases commitment to lytic infection and can lead to reactivation of quiescent or latent viral genomes (reviewed in reference 10). Mol Biol Evol 3: 418-426. These results are consistent with accumulating data from other laboratories and support the current model of DNA mismatch repair in mammalian cells. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with ∼25% of the genome being devoid of polymorphisms. Additionally, the median HSV-tk mutation rate of single-cell clones carrying the[ TC/AG]17 vector was significantly different from that of clones harboring the control vector.

TK + trypanosomes, however, reverted to a ganciclovir resistant phenotype at a rate of 10 −6 per cell-generation. It would be simple for them to delete their proofreading domain. The factors that influence the relative utilization of gene inactivation pathways are poorly understood. As the HSV-tk coding sequence contains an endogenous [G/C]7 mononucleotide repeat and ~1000 bp of unique sequence, we were able to compare mutagenesis among various sequence motifs. Here, we compared the activities of the gB:NT variant with those of a newly selected variant of glycoprotein H (gH:KV) and a frequently coselected gB variant (gB:S668N). An inherent limitation of the activity of HSV-TK is the >70-fold difference in the Kms for phosphorylation of thymidine over the pro-drug ganciclovir (GCV). There followed a burst of investigations into the mutation process in phage T4.

Our site uses cookies to improve your experience. We have examined mutational events at TC/AG microsatellites, the second most abundant dinucleotide repetitive motif in the human genome. This article has been cited by other articles in PMC. Herpes simplex virus 1 (HSV-1) causes recurrent mucocutaneous ulcers and is the leading cause of infectious blindness and sporadic encephalitis in the United States. Many years after the patient has recovered from chickenpox, VZV can reactivate to cause a number of neurologic conditions. Our site uses cookies to improve your experience. The mutation rate of an organism is defined as the probability that a change in genetic information is passed to the next generation.

Please check the format of the address you have entered. The capacity of RNA viruses to produce prodigious numbers of mutations is a powerful advantage.