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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6950143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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