The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31.
The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31.
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DOI：
10.3390/pathogens9100786
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发表时间：
2020-09-25
期刊：
影响因子：
--
通讯作者：
Androphy EJ
中科院分区：
文献类型：
--
作者：
Gibson RT;Androphy EJ
染色体多亚单位结构维持（SMC） 5/6复合体包括SMC6和非SMC元件（NSE）3。SMC5/6对同源重组DNA修复至关重要，并在乙型肝炎（HBV）和单纯疱疹病毒（HSV-1）感染中作为抗病毒因子发挥作用。有趣的是，SMC5/6已被发现与高危人乳头瘤病毒（HPV） E2调节蛋白相关，但这种相互作用的功能及其在HPV感染中的作用尚不清楚。在这里，我们进一步表征SMC5/6与HPV- 31e2的相互作用及其在HPV生命周期中的作用。共免疫沉淀（co-IP）显示SMC6与HPV-31 E2的相互作用需要E2的反活化结构域，这表明SMC5/6与全长E2相互作用。通过染色质免疫沉淀，我们发现SMC6存在于HPV-31亚型E2结合位点上。SMC6和NSE3的缺失增加了维持episomal HPV-31的角化细胞中的病毒复制和转录，表明SMC5/6限制了病毒的复制程序。当HPV-31 E1存在时，SMC6与E2的相互作用减弱，表明SMC6和E1竞争E2的结合。我们的研究结果表明SMC5/6具有抑制病毒复制程序的功能，这可能涉及抑制病毒复制的启动。
The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, SMC5/6 has been found to associate with high-risk human papillomavirus (HPV) E2 regulatory proteins, but the functions of this interaction and its role during HPV infection remain unclear. Here, we further characterize SMC5/6 interactions with HPV-31 E2 and its role in the HPV life cycle. Co-immunoprecipitation (co-IP) revealed that SMC6 interactions with HPV-31 E2 require the E2 transactivation domain, implying that SMC5/6 interacts with full-length E2. Using chromatin immunoprecipitation, we found that SMC6 is present on HPV-31 episomes at E2 binding sites. The depletion of SMC6 and NSE3 increased viral replication and transcription in keratinocytes maintaining episomal HPV-31, indicating that SMC5/6 restricts the viral replicative program. SMC6 interactions with E2 were reduced in the presence of HPV-31 E1, suggesting that SMC6 and E1 compete for E2 binding. Our findings demonstrate SMC5/6 functions as a repressor of the viral replicative program and this may involve inhibiting the initiation of viral replication.
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影响因子：
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