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Open AccessCommunication

Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication

1
UMR 1092, INSERM, CHU Limoges, Université Limoges, F-87000 Limoges, France
2
Laboratoire de Bactériologie-Virologie-Hygiène, National Reference Center for Herpesviruses (NRCHV), CHU Limoges, F-87000 Limoges, France
*
Authors to whom correspondence should be addressed.
Current address: Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, 67000 Strasbourg, France.
Viruses 2019, 11(12), 1093; https://doi.org/10.3390/v11121093
Received: 16 October 2019 / Revised: 21 November 2019 / Accepted: 22 November 2019 / Published: 26 November 2019
(This article belongs to the Special Issue Recent Advances in Herpesviruses Research: What's in the Pipeline?)
The human cytomegalovirus (HCMV) terminase complex is part of DNA-packaging machinery that delivers a unit-length genome into a procapsid. Sequence comparison of herpesvirus homologs allowed us to identify a potential LATLNDIERFL and zinc finger pattern in N-terminal part of pUL56. Recombinant viruses were generated with specific serine or alanine substitutions in these putative patterns. We identified a LATLNDIERFL pattern characteristic of LAGLIDADG homing endonucleases and a metal-binding pattern involving the cysteine and histidine residues C191-X2-C194-X22-C217-X-H219 (CCCH) close to the region conferring letermovir resistance. These patterns are crucial for viral replication, suggesting that they are essential for pUL56 structure and function. Thus, these patterns represent potential targets for the development of new antivirals such as small molecules or peptides and may allow to better understand the letermovir mechanism of action. View Full-Text
Keywords: human cytomegalovirus; terminase; targets; functional domains human cytomegalovirus; terminase; targets; functional domains
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MDPI and ACS Style

Ligat, G.; Couvreux, A.; Cazal, R.; Alain, S.; Hantz, S. Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication. Viruses 2019, 11, 1093.

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