Human cytomegalovirus (CMV) susceptibility to currently approved antiviral drugs does not impact on CMV terminase complex polymorphism

• Published in: Antiviral research Vol. 111; pp. 8 - 12
• Main Authors: Pilorgé, Léa, Burrel, Sonia, Aït-Arkoub, Zaïna, Agut, Henri, Boutolleau, David
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.11.2014; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Biological and medical sciences; Cytomegalovirus - classification; Cytomegalovirus - drug effects; Cytomegalovirus - enzymology; Cytomegalovirus - genetics; Cytomegalovirus Infections - virology; Drug Resistance, Viral; Endodeoxyribonucleases - genetics; Endodeoxyribonucleases - metabolism; Human cytomegalovirus; Humans; Medical sciences; Natural polymorphism; Pharmacology. Drug treatments; Phylogeny; Polymorphism, Genetic; Resistance to DNA polymerase inhibitors; Terminase complex; Viral Proteins - genetics; Viral Proteins - metabolism; Viral Structural Proteins - genetics; Viral Structural Proteins - metabolism; Terminase complex; Resistance to DNA polymerase inhibitors; Natural polymorphism; Human cytomegalovirus; Drug; Herpesviridae; Betaherpesvirinae; Virus; Resistance; Sensitivity; Antiviral; DNA polymerase inhibitor; Polymorphism
• ISSN: 0166-3542; 1872-9096; 1872-9096
• DOI: 10.1016/j.antiviral.2014.08.014

•CMV terminase complex is a promising target for new antivirals.•Identification of novel mutations accounting for the natural polymorphism of CMV terminase complex.•No influence of CMV susceptibility to currently approved antivirals on the natural polymorphism of CMV terminase complex. Currently approved anti-human cytomegalovirus (CMV) drugs, all targeting the viral DNA polymerase, are associated with significant toxicities and emergence of drug resistance. In this context, CMV terminase complex constitutes a promising target for novel antiviral compounds. In this study, we describe the low natural polymorphism (interstrain identity >97.7% at both nucleotide and amino acid levels) of the terminase subunits pUL56 and pUL89, and the portal protein pUL104, among 63 CMV clinical strains, and we show that the CMV resistance profile to current DNA polymerase inhibitors has no impact on the natural polymorphism of CMV terminase complex. These results support the idea that both CMV clinical strains exhibiting either susceptibility or resistance to current CMV DNA polymerase inhibitors are comparably sensitive to novel inhibitors of CMV terminase complex, such as letermovir.