Endogenous latent membrane protein 1 in Epstein-Barr virus-infected nasopharyngeal carcinoma cells attracts T lymphocytes through upregulation of multiple chemokines.
Tumor-infiltrating T lymphocytes are considered to facilitate development of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), but how EBV in NPC tumor cells directs T cell infiltration remains unclear. Here we compare EBV-infected NPC cells with and without spontaneous expression of viral latent membrane protein 1 (LMP1) and find that culture supernatants of LMP1-positive NPC cells exert enhanced chemoattraction to primary T cells. Knockdown of endogenous LMP1 in the cells suppresses the chemotactic activity. Endogenous LMP1 in NPC cells upregulates multiple chemokines, among which MIP-1alpha, MIP-1beta and IL-8 contribute to T cell chemotaxis. We further reveal that LMP1-induced production of MIP-1alpha and MIP-1beta in NPC cells requires not only two carboxyl-terminal activation regions of LMP1 but also their downstream NF-kappaB and JNK pathways. This study corroborates that endogenous LMP1 in EBV-infected NPC cells induces multiple chemokines to promote T cell recruitment and perhaps other pathogenic events in NPC.
Lai
Hsiao-Ching
HC
Division of Infectious Diseases, National Health Research Institutes, Tainan, Taiwan.
Hsiao
Jenn-Ren
JR
Chen
Chaio-Wei
CW
Wu
Shih-Yi
SY
Lee
Chien-Hsun
CH
Su
Ih-Jen
IJ
Takada
Kenzo
K
Chang
Yao
Y
D002277:Carcinoma / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000821:virology*; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins