Human Cytomegalovirus DNA Polymerase Subunit UL44 Antagonizes Antiviral Immune Responses by Suppressing IRF3-and NF-kappa B-Mediated Transcription
文献类型：期刊论文
| 作者 | Fu, Yu-Zhi1; Su, Shan2; Zou, Hong-Mei1; Guo, Yi2; Wang, Su-Yun1; Li, Shu2; Luo, Min-Hua1; Wang, Yan-Yi1 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2019-06-01 |
| 卷号 | 93期号:11页码:13 |
| 关键词 | HCMV IRF3 NF-kappa B UL44 immune evasion innate immunity type I interferons |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.00181-19 |
| 英文摘要 | Innate immunity is the first line of host defense against viral invasion. The induction of type I interferons (IFNs) and inflammatory cytokines is essential to host antiviral immune responses, which are also key targets of viral immune evasion. Human cytomegalovirus (HCMV) can establish long-term latent infections, in which immune evasion is a pivotal step. In this study, we identified HCMV protein UL44, a DNA polymerase processivity factor, as an inhibitor of the interferon regulatory factor 3 (IRF3)- and NF-kappa B-dependent antiviral response. Ectopic expression of UL44 inhibited HCMV-triggered induction of downstream effector genes and enhanced viral replication. Conversely, knockdown of UL44 potentiated HCMV-triggered induction of downstream antiviral genes. UL44 interacted with IRF3 and p65, and it inhibited the binding of IRF3 and NF-kappa B to the promoters of their downstream antiviral genes. These findings reveal an important mechanism of immune evasion by HCMV at the transcriptional level. IMPORTANCE Induction of type I IFNs and inflammatory cytokines plays pivotal roles in host antiviral innate immune responses. Viruses have evolved various mechanisms to interfere with these processes. HCMV causes severe ailments in immunodeficient populations and is a major cause of birth defects. It has been shown that HCMV antagonizes host innate immune defenses, which is important for establishing immune evasion and latent infection. In this study, we identified the HCMV DNA polymerase subunit UL44 as a suppressor of antiviral innate immune responses. Overexpression of UL44 impaired HCMV-triggered induction of type I IFNs and other antiviral genes and thus potentiated viral replication, whereas UL44 deficiency showed opposite effects. Mechanistic studies indicated that UL44 acts by inhibiting the binding of IRF3 and NF-kappa B to the promoters of downstream antiviral genes. These findings defined an important mechanism of HCMV immune evasion at the transcriptional level, which may provide a therapeutic target for the treatment of HCMV infection. |
| 资助项目 | National Science Fund for Distinguished Young Scholars[31425010] ; Pilot Project of Chinese Academy of Sciences (CAS)[XDB29010302] ; National Natural Science Foundation of China[31621061] ; National Natural Science Foundation of China[31800732] ; Ministry of Science and Technology of China[2015CB554302] ; Key Research Programs of Frontier Sciences (Chinese Academy of Sciences) ; National Postdoctoral Program for Innovative Talents[BX201700277] ; China Postdoctoral Science Foundation[2018M630894] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000467925600009 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/7712]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Wang, Yan-Yi |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China 2.Wuhan Univ, Sch Med, Med Res Inst, Wuhan, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fu, Yu-Zhi,Su, Shan,Zou, Hong-Mei,et al. Human Cytomegalovirus DNA Polymerase Subunit UL44 Antagonizes Antiviral Immune Responses by Suppressing IRF3-and NF-kappa B-Mediated Transcription[J]. JOURNAL OF VIROLOGY,2019,93(11):13. |
| APA | Fu, Yu-Zhi.,Su, Shan.,Zou, Hong-Mei.,Guo, Yi.,Wang, Su-Yun.,...&Wang, Yan-Yi.(2019).Human Cytomegalovirus DNA Polymerase Subunit UL44 Antagonizes Antiviral Immune Responses by Suppressing IRF3-and NF-kappa B-Mediated Transcription.JOURNAL OF VIROLOGY,93(11),13. |
| MLA | Fu, Yu-Zhi,et al."Human Cytomegalovirus DNA Polymerase Subunit UL44 Antagonizes Antiviral Immune Responses by Suppressing IRF3-and NF-kappa B-Mediated Transcription".JOURNAL OF VIROLOGY 93.11(2019):13. |
入库方式： OAI收割
来源：武汉植物园
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