Nonmuscle myosin heavy chain IIA mediates Epstein-Barr virus infection of nasopharyngeal epithelial cells

被引:78
作者
Xiong, Dan [1 ]
Du, Yong [1 ]
Wang, Hong-Bo [1 ]
Zhao, Bo [2 ,3 ]
Zhang, Hua [1 ]
Li, Yan [1 ]
Hu, Li-Juan [1 ]
Cao, Jing-Yan [1 ]
Zhong, Qian [1 ]
Liu, Wan-Li [1 ]
Li, Man-Zhi [1 ]
Zhu, Xiao-Feng [1 ]
Tsao, Sai Wah [4 ,5 ]
Hutt-Fletcher, Lindsey M. [6 ]
Song, Erwei [7 ]
Zeng, Yi-Xin [1 ]
Kieff, Elliott [2 ,3 ]
Zeng, Mu-Sheng [1 ]
机构
[1] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, State Key Lab Oncol South China,Collaborat Innova, Guangzhou 510060, Guangdong, Peoples R China
[2] Brigham & Womens Hosp, Dept Med & Microbiol & Immunobiol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Univ Hong Kong, Dept Anat, Hong Kong, Hong Kong, Peoples R China
[5] Univ Hong Kong, Ctr Canc Res, Hong Kong, Hong Kong, Peoples R China
[6] Louisiana State Univ, Dept Microbiol & Immunol, Hlth Sci Ctr, Shreveport, LA 71130 USA
[7] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China
基金
中国国家自然科学基金;
关键词
Epstein-Barr virus; nasopharyngeal carcinoma; NMHC-IIA; gH/gL; BMI1; B-CELLS; CONFORMATIONAL-CHANGE; GLYCOPROTEINS GHGL; FUSION; ENTRY; EBV; RECEPTOR; CARCINOMA; BINDING; ALPHA-V-BETA-8;
D O I
10.1073/pnas.1513359112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
EBV causes B lymphomas and undifferentiated nasopharyngeal carcinoma (NPC). Although the mechanisms by which EBV infects B lymphocytes have been extensively studied, investigation of the mechanisms by which EBV infects nasopharyngeal epithelial cells (NPECs) has only recently been enabled by the successful growth of B lymphoma Mo-MLV insertion region 1 homolog (BMI1)-immortalized NPECs in vitro and the discovery that neuropilin 1 expression positively affects EBV glycoprotein B (gB)-mediated infection and tyrosine kinase activations in enhancing EBV infection of BMI1-immortalized NPECs. We have now found that even though EBV infected NPECs grown as a monolayer at extremely low efficiency (<3%), close to 30% of NPECs grown as sphere-like cells (SLCs) were infected by EBV. We also identified nonmuscle myosin heavy chain IIA (NMHC-IIA) as another NPEC protein important for efficient EBV infection. EBV gH/gL specifically interacted with NMHC-IIA both in vitro and in vivo. NMHC-IIA densely aggregated on the surface of NPEC SLCs and colocalized with EBV. EBV infection of NPEC SLCs was significantly reduced by NMHC-IIA siRNA knock-down. NMHC-IIA antisera also efficiently blocked EBV infection. These data indicate that NMHC-IIA is an important factor for EBV NPEC infection.
引用
收藏
页码:11036 / 11041
页数:6
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