Analysis of LMP1 variants of EBV in Southern Thailand: evidence for strain-associated T-cell tropism and pathogenicity.
BACKGROUND
The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) has sequence heterogeneity. Some of the variants are associated with altered tumorigenic activity and show geographically specific localization. In Thailand, the EBV genome is frequently detected in circulating T cells of T-cell diseases.


OBJECTIVE
To determine the role of EBV LMP1 variation in the genesis of T-cell diseases, we focused on virus factors and analyzed EBV strains in Thailand.


METHODS
EBV DNA was extracted from 18 healthy individuals and 45 patients with T-cell diseases in Southern Thailand and 30 healthy individuals in Central Thailand. By using PCR-direct sequencing method, nucleotide sequences corresponding to the carboxyl terminus of the LMP1 were determined.


RESULTS
Four known strains, B95-8 prototype, China 1, China 2 and Mediterranean (Med) and two novel strains, Southeast Asia 1 (SEA 1) and Southeast Asia 2 (SEA 2) were identified. The prevalence of China 2 strain was significantly different (p=0.006) between Central and Southern Thailand. Higher prevalence (p=0.026) of 30-bp deletion type in the Southern Thais was observed. The LMP1 Med strain was associated with the worse prognosis (p=0.029). Among T-cell diseases patients, CD3(+)-cell oriented infection was recognized in SEA1 strain (p=0.025).


CONCLUSIONS
The distribution of EBV strains may be associated with geographic/ethnic and clinical background in the Thai population. Certain EBV strains defined by their LMP1 sequence may influence cell tropism, disease association, or disease severity.
Saechan
Vannarat
V
Unit of Human Biology and Genetics, Department of Biological Sciences, Graduate, School of Science, University of Tokyo, Tokyo, Japan.
Mori
Atsumi
A
Mitarnun
Winyou
W
Settheetham-Ishida
Wannapa
W
Ishida
Takafumi
T
D000595:Amino Acid Sequence; D017252:CD3 Complex; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D005814:Genes, Viral; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D016399:Lymphoma, T-Cell / Q000821:virology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013785:Thailand; D014763:Viral Matrix Proteins / Q000235:genetics*; D014774:Virulence / Q000276:immunology
D017252:CD3 Complex; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins