The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling
Minute Virus of Mice (MVM) is an autonomous parvovirus of the <i>Parvoviridae</i> family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/6/1243 |
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| author | Clairine I. S. Larsen Kinjal Majumder |
| author_facet | Clairine I. S. Larsen Kinjal Majumder |
| author_sort | Clairine I. S. Larsen |
| collection | DOAJ |
| description | Minute Virus of Mice (MVM) is an autonomous parvovirus of the <i>Parvoviridae</i> family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 localization to cellular DDR sites is independent of ATM or DNA-PK signaling but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication. |
| first_indexed | 2024-03-11T01:50:08Z |
| format | Article |
| id | doaj.art-7e1dea735add47ce97b6decb12adee66 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T01:50:08Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-7e1dea735add47ce97b6decb12adee662023-11-18T13:01:00ZengMDPI AGViruses1999-49152023-05-01156124310.3390/v15061243The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR SignalingClairine I. S. Larsen0Kinjal Majumder1Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, USAInstitute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, USAMinute Virus of Mice (MVM) is an autonomous parvovirus of the <i>Parvoviridae</i> family that replicates in mouse cells and transformed human cells. MVM genomes localize to cellular sites of DNA damage with the help of their essential non-structural phosphoprotein NS1 to establish viral replication centers. MVM replication induces a cellular DNA damage response that is mediated by signaling through the ATM kinase pathway, while inhibiting induction of the ATR kinase signaling pathway. However, the cellular signals regulating virus localization to cellular DNA damage response sites has remained unknown. Using chemical inhibitors to DNA damage response proteins, we have discovered that NS1 localization to cellular DDR sites is independent of ATM or DNA-PK signaling but is dependent on ATR signaling. Pulsing cells with an ATR inhibitor after S-phase entry leads to attenuated MVM replication. These observations suggest that the initial localization of MVM to cellular DDR sites depends on ATR signaling before it is inactivated by vigorous virus replication.https://www.mdpi.com/1999-4915/15/6/1243parvovirusesDNA damage responseMinute Virus of Mice |
| spellingShingle | Clairine I. S. Larsen Kinjal Majumder The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling Viruses parvoviruses DNA damage response Minute Virus of Mice |
| title | The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling |
| title_full | The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling |
| title_fullStr | The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling |
| title_full_unstemmed | The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling |
| title_short | The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling |
| title_sort | autonomous parvovirus minute virus of mice localizes to cellular sites of dna damage using atr signaling |
| topic | parvoviruses DNA damage response Minute Virus of Mice |
| url | https://www.mdpi.com/1999-4915/15/6/1243 |
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