ArticleJournal of virology2012
Mutations conferring resistance to viral DNA polymerase inhibitors in camelpox virus give different drug-susceptibility profiles in vaccinia virus.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
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- Monkeypox: a re-emergent virus with global health implications - a comprehensive review.Tropical diseases, travel medicine and vaccines · 2025Review
- Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses.Genomics, proteomics & bioinformatics · 2024Article
- Small-Angle X-Ray Scattering for Macromolecular Complexes.Advances in experimental medicine and biology · 2024Article
- Emergence of monkeypox: a worldwide public health crisis.Human cell · 2023Review
- Repositioning potentials of smallpox vaccines and antiviral agents in monkeypox outbreak: A rapid review on comparative benefits and risks.Health science reports · 2022Article
- Poxviruses Bearing DNA Polymerase Mutations Show Complex Patterns of Cross-Resistance.Biomedicines · 2022Article
- Article
- Meta-iAVP: A Sequence-Based Meta-Predictor for Improving the Prediction of Antiviral Peptides Using Effective Feature Representation.International journal of molecular sciences · 2019Article
- Antiviral peptides as promising therapeutic drugs.Cellular and molecular life sciences : CMLS · 2019Review
- The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding.Nature communications · 2017Article
- Article
- The vaccinia virus DNA polymerase and its processivity factor.Virus research · 2017Review
- ST-246 is a key antiviral to inhibit the viral F13L phospholipase, one of the essential proteins for orthopoxvirus wrapping.The Journal of antimicrobial chemotherapy · 2015Article
- KAY-2-41, a novel nucleoside analogue inhibitor of orthopoxviruses in vitro and in vivo.Antimicrobial agents and chemotherapy · 2014Article
- Orthopoxvirus inhibitors that are active in animal models: an update from 2008 to 2012.Future virology · 2013Article
- Emergence of cowpox: study of the virulence of clinical strains and evaluation of antivirals.PloS one · 2013Article
- Potential therapeutic targets for Mpox: the evidence to date.Expert opinion on therapeutic targetsArticle
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cidofovir or (S)-HPMPC is one of the three antiviral drugs that might be used for the treatment of orthopoxvirus infections. (S)-HPMPC and its 2,6-diaminopurine counterpart, (S)-HPMPDAP, have been described to select, in vitro, for drug resistance mutations in the viral DNA polymerase (E9L) gene of vaccinia virus (VACV). Here, to extend our knowledge of drug resistance development among orthopoxviruses, we selected, in vitro, camelpox viruses (CMLV) resistant to (S)-HPMPDAP and identified a single amino acid change, T831I, and a double mutation, A314V+A684V, within E9L. The production of recombinant CMLV and VACV carrying these amino acid substitutions (T831I, A314V, or A314V+A684V) demonstrated clearly their involvement in conferring reduced sensitivity to viral DNA polymerase inhibitors, including (S)-HPMPDAP. Both CMLV and VACV harboring the A314V change showed comparable drug-susceptibility profiles to various antivirals and similar impairments in viral growth. In contrast, the single change T831I and the double change A314V+A684V in VACV were responsible for increased levels of drug resistance and for cross-resistance to viral DNA polymerase antivirals that were not observed with their CMLV counterparts. Each amino acid change accounted for an attenuated phenotype of VACV in vivo. Modeling of E9L suggested that the T→I change at position 831 might abolish hydrogen bonds between E9L and the DNA backbone and have a direct impact on the incorporation of the acyclic nucleoside phosphonates. Our findings demonstrate that drug-resistance development in two related orthopoxvirus species may impact drug-susceptibility profiles and viral fitness differently.
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