Nonmuscle myosin heavy chain IIA mediates Epstein-Barr virus infection of nasopharyngeal epithelial cells.
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.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Dan
D
Xiong
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Yong
Y
Du
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Hong-Bo
HB
Wang
Department of Medicine and Microbiology and Immunobiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Bo
B
Zhao
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Hua
H
Zhang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Yan
Y
Li
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Li-Juan
LJ
Hu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Jing-Yan
JY
Cao
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Qian
Q
Zhong
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Wan-Li
WL
Liu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Man-Zhi
MZ
Li
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Xiao-Feng
XF
Zhu
Department of Anatomy and Center for Cancer Research, University of Hong Kong, Hong Kong, Special Administrative Region 999077, People's Republic of China;
Sai Wah
SW
Tsao
Health Science Center, Department of Microbiology and Immunology, Louisiana State University, Shreveport, LA 71130;
Lindsey M
LM
Hutt-Fletcher
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People's Republic of China.
Erwei
E
Song
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China;
Yi-Xin
YX
Zeng
Department of Medicine and Microbiology and Immunobiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; ekieff@rics.bwh.harvard.edu zengmsh@mail.sysu.edu.cn.
Elliott
E
Kieff
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China; ekieff@rics.bwh.harvard.edu zengmsh@mail.sysu.edu.cn.
Mu-Sheng
MS
Zeng
D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D020031:Epstein-Barr Virus Infections / Q000503:physiopathology*; D006801:Humans; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000502:physiology*; D009305:Nasopharynx / Q000473:pathology / Q000821:virology*
D018995:Myosin Heavy Chains
BMI1; Epstein–Barr virus; NMHC-IIA; gH/gL; nasopharyngeal carcinoma