Abstract
The human cytomegalovirus (HCMV) DNA polymerase is composed of the UL54 catalytic subunit and the UL44 accessory protein. UL44 increases the processivity of polymerase along the DNA template during replication and, incidentally, is a substrate for the UL97 phosphotransferase. The molecular mechanisms of HCMV resistance to antiviral drugs interfering with viral DNA synthesis reported so far only rely on the presence of amino acid changes within the UL97 and UL54 viral enzymes. We aimed to describe the natural polymorphism of UL44 and to analyse the changes of its amino acids potentially associated with HCMV resistance to antivirals. The full-length UL44 gene sequence was compared to that of four reference strains (including the AD169 strain) and 43 clinical strains from patients who had not received any previous anti-HCMV treatment, and 25 blood samples from 15 HCMV-infected patients experiencing therapeutic failure and exhibiting genotypic traits of HCMV resistance to antivirals. Overall, seven different amino acid changes associated with natural polymorphisms were identified among the 433 residues of the UL44 protein, occurring at a frequency of 2.1% for five of them and 10.6% for the double change G296S+L319I. The analysis of the HCMV strains exhibiting genotypic resistance to antivirals did not show any changes in UL44 that had significant association with resistance mutations of UL97 and/or UL54. UL44 processivity factor exhibits a very low polymorphism that does not concern the assumed functional domains of the protein. From this preliminary study, UL44 does not seem to be involved in HCMV resistance to antivirals.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.