ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway
Summary: Kaposi’s sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that exhibits two alternative life cycles: latency and lytic reactivation. During lytic reactivation, host innate immune responses are activated to restrict viral replication. Here, we report that adenosine deamin...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720305131 |
| _version_ | 1811207434437394432 |
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| author | Huirong Zhang Guoxin Ni Blossom Damania |
| author_facet | Huirong Zhang Guoxin Ni Blossom Damania |
| author_sort | Huirong Zhang |
| collection | DOAJ |
| description | Summary: Kaposi’s sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that exhibits two alternative life cycles: latency and lytic reactivation. During lytic reactivation, host innate immune responses are activated to restrict viral replication. Here, we report that adenosine deaminase acting on RNA 1 (ADAR1) is required for optimal KSHV lytic reactivation from latency. Knockdown of ADAR1 in KSHV latently infected cells inhibits viral gene transcription and viral replication during KSHV lytic reactivation. ADAR1 deficiency also significantly increases type I interferon production during KSHV reactivation. This increased interferon response is dependent on activation of the RIG-I-like receptor (RLR) pathway. Depletion of ADAR1 together with either RIG-I, MDA5, or MAVS reverses the increased IFNβ production and rescues KSHV lytic replication. These data suggest that ADAR1 serves as a proviral factor for KSHV lytic reactivation and facilitates DNA virus reactivation by dampening the RLR pathway-mediated innate immune response. : Zhang et al. report that ADAR1, a double-stranded RNA-editing enzyme, can facilitate KSHV reactivation by dampening the RIG-I/MDA5 pathway-mediated innate immune response. This study sheds light on how host cell proteins modulate the KSHV life cycle. Keywords: KSHV, RLR, MDA5, RIG-I, ADAR1 |
| first_indexed | 2024-04-12T04:02:55Z |
| format | Article |
| id | doaj.art-7f212bad88294688b9c045398d0131a8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T04:02:55Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7f212bad88294688b9c045398d0131a82022-12-22T03:48:40ZengElsevierCell Reports2211-12472020-04-01314ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling PathwayHuirong Zhang0Guoxin Ni1Blossom Damania2Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, and Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, and Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, and Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Corresponding authorSummary: Kaposi’s sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that exhibits two alternative life cycles: latency and lytic reactivation. During lytic reactivation, host innate immune responses are activated to restrict viral replication. Here, we report that adenosine deaminase acting on RNA 1 (ADAR1) is required for optimal KSHV lytic reactivation from latency. Knockdown of ADAR1 in KSHV latently infected cells inhibits viral gene transcription and viral replication during KSHV lytic reactivation. ADAR1 deficiency also significantly increases type I interferon production during KSHV reactivation. This increased interferon response is dependent on activation of the RIG-I-like receptor (RLR) pathway. Depletion of ADAR1 together with either RIG-I, MDA5, or MAVS reverses the increased IFNβ production and rescues KSHV lytic replication. These data suggest that ADAR1 serves as a proviral factor for KSHV lytic reactivation and facilitates DNA virus reactivation by dampening the RLR pathway-mediated innate immune response. : Zhang et al. report that ADAR1, a double-stranded RNA-editing enzyme, can facilitate KSHV reactivation by dampening the RIG-I/MDA5 pathway-mediated innate immune response. This study sheds light on how host cell proteins modulate the KSHV life cycle. Keywords: KSHV, RLR, MDA5, RIG-I, ADAR1http://www.sciencedirect.com/science/article/pii/S2211124720305131 |
| spellingShingle | Huirong Zhang Guoxin Ni Blossom Damania ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway Cell Reports |
| title | ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway |
| title_full | ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway |
| title_fullStr | ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway |
| title_full_unstemmed | ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway |
| title_short | ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway |
| title_sort | adar1 facilitates kshv lytic reactivation by modulating the rlr dependent signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720305131 |
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