Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency

Beaucourt, Stéphanie; Bordería, Antonio V.; Coffey, Lark L.; Gnädig, Nina F.; Sanz-Ramos, Marta; Beeharry, Yasnee; Mouquet, Hugo

doi:10.3791/2953-v

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…To date, one hypermutator has been identified in HCMV ( Chou et al 2016 ). Mutator alleles are a double-edged sword for viruses, having important implications for the rate of adaption ( Taddei et al 1997 ; Travis and Travis 2002 ), but more significantly also create the possibility of mutational meltdown ( Crotty et al 2001 ; Beaucourt et al 2011 ; Bank et al 2016 ; Matuszewski et al 2017 ; Ormond et al 2017 ). Indeed, owing to interference between the greater input of deleterious mutations with the minor input of beneficial mutations, higher mutation rates may slow or stop the rate of adaptation ( Pénisson et al 2017 ; Jensen and Lynch 2020 ; Jensen et al 2020 ).…”

Section: Mutation Ratementioning

confidence: 99%

Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus

Howell

Terbot

Soni

et al. 2023

Genome Biology and Evolution

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Human cytomegalovirus (HCMV) represents a major threat to human health, contributing to both birth defects in neonates as well as organ transplant failure and opportunistic infections in immunocompromised individuals. HCMV exhibits considerable inter- and intra-host diversity, which likely influences the pathogenicity of the virus. Therefore, understanding the relative contributions of various evolutionary forces in shaping patterns of variation is of critical importance both mechanistically as well as clinically. Herein we present the individual components of an evolutionary baseline model for HCMV, with a particular focus on congenital infections for the sake of illustration – including mutation and recombination rates, the distribution of fitness effects, infection dynamics, as well as compartmentalization – and describe the current state of knowledge of each. By building this baseline model, researchers will be able to better describe the range of possible evolutionary scenarios contributing to observed variation, as well as improve power and reduce false-positive rates when scanning for adaptive mutations in the HCMV genome.

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Section: Mutation Ratementioning

confidence: 99%

Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus

Howell

Terbot

Soni

et al. 2023

Genome Biology and Evolution

View full text Add to dashboard Cite

show abstract

“…In addition to 5-FU, base analogues include ribavirin (guanosine analogue) and 5-azacytidine (cytidine analogue). These mutagenic compounds affect both RNA and DNA viruses [8,[17][18][19][20]. The current study investigates effects of 5-FU on the KOS strain of HSV-1, a clinically important DNA virus.…”

Section: Passage No Genbank Nomentioning

confidence: 99%

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

TASKIN¹

2022

FARMACIA

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Two pandemics over the first two decades of the 21 st 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 type-1 (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. RezumatPandemiile din primele decenii ale secolului XXI au arătat că virusurile cu potențial epidemic și pandemic constituie o amenințare majoră pentru sănătatea umană din cauza lipsei de medicamente antivirale eficiente. Dezvoltarea de noi antivirale și de noi strategii de tratament este la fel de importantă ca și vaccinurile care joacă un rol important în prima linie de prevenție a infecțiilor virale. Utilizarea analogilor de baze care țintesc direct virusurile și înțelegerea mecanismelor de acțiune ale acestora pot reprezenta strategii de tratament alternative esențiale pentru combaterea bolilor virale. Studiul de față a investigat efectele unui analog de bază asupra replicării virusului herpes simplex de tip 1 (HSV-1) într-un sistem de cultură celular, și anume analogul pirimidinic 5-fluorouracil (FU). Ulterior, a fost secvențiată gena UL-23 de lungime completă care codifică timidin kinaza (TK) a HSV-1 pentru a detecta mutațiile induse. Rezultatele au arătat o scădere a titrului viral și a încărcăturii virale de 2 log și, respectiv, de 663 de ori, la sfârșitul a 10 treceri consecutive cu 5-FU. În plus, au fost identificate și două mutații care înlocuiesc aminoacizii din regiunea neconservată a genei TK, ce conferă rezistență la medicamente.

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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency

Cited by 2 publications

References 7 publications

Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus

Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus

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

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