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

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 virus...

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Autores principales: Ligat, Gaëtan, Couvreux, Anthony, Cazal, Raphaël, Alain, Sophie, Hantz, Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950143/
https://www.ncbi.nlm.nih.gov/pubmed/31779110
http://dx.doi.org/10.3390/v11121093
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author Ligat, Gaëtan
Couvreux, Anthony
Cazal, Raphaël
Alain, Sophie
Hantz, Sébastien
author_facet Ligat, Gaëtan
Couvreux, Anthony
Cazal, Raphaël
Alain, Sophie
Hantz, Sébastien
author_sort Ligat, Gaëtan
collection PubMed
description 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 C(191)-X2-C(194)-X22-C(217)-X-H(219) (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.
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spelling pubmed-69501432020-01-13 Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication Ligat, Gaëtan Couvreux, Anthony Cazal, Raphaël Alain, Sophie Hantz, Sébastien Viruses Communication 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 C(191)-X2-C(194)-X22-C(217)-X-H(219) (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. MDPI 2019-11-26 /pmc/articles/PMC6950143/ /pubmed/31779110 http://dx.doi.org/10.3390/v11121093 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Ligat, Gaëtan
Couvreux, Anthony
Cazal, Raphaël
Alain, Sophie
Hantz, Sébastien
Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication
title Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication
title_full Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication
title_fullStr Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication
title_full_unstemmed Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication
title_short Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication
title_sort highlighting of a laglidadg and a zing finger motifs located in the pul56 sequence crucial for hcmv replication
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950143/
https://www.ncbi.nlm.nih.gov/pubmed/31779110
http://dx.doi.org/10.3390/v11121093
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