Abstract
The latent EBV gene products expressed in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), are only LMP2A, EBNA-1, BARF-0 and EBERs. To examine the correlation between LMP2A sequence variation in EBVaGC and transformation of the cells, the complete sequence of the LMP2A gene was determined in three cases of Japanese EBVaGC and compared with the prototype B95-8 strain. In addition, the sequences of exons 2,6 and 7 of LMP2A were determined in four to six EBVaGC cases. The results of sequence analysis indicated that LMP2A of EBVaGC was structurally very similar to B95-8, but contained a significant nucleotide variation. Ten nucleotide substitutions were identified in almost all cases tested, and three of these caused amino acid changes. Of these three, two amino acid substitutions were not expected to change any known functions of LMP2A. The other amino acid substitution from serine to threonine was located at codon 348 within one of the target epitopes of EBV-specific cytotoxic T-lymphocytes. The LMP2A of EBV in peripheral blood lymphocytes from six healthy individuals showed serine (4/6 cases) or threonine (2/6 cases) substitution at codon 348, while LMP2A with the threonine substitution was the major form (5/6 cases) observed in EBVaGC, indicating that EBV with the threonine substitution may confer an advantage for viral persistence in tumor cells. However, our sequencing results suggested that the LMP2A protein in EBVaGC is functionally similar to that of the B95-8 strain and is not unique to gastric carcinoma, indicating the importance of LMP2A for EBV latency.
Similar content being viewed by others
References
Rickinson A.B. and Kieff E., Fields Virology 3 (B.N.Fields et al. 3rd ed.) Raven Press, New York, p. 2397-2447, 1996.
Ott G., Kirchner T.H., and Muller-Hermelink H.K., Histopathol 25, 323-329, 1994.
Liebowitz D. and Kieff E., In The Human Herpesvirus. 107-172, 1993.
Gilligan K., Sato H., Rajadurai P., Busson P., Young L., Rickinson A., Tursz T., and Raab-Traub N., J Virol 64, 4948-4956, 1990.
Qu L. and Rowe D.T., J Virol 66, 3715-3724, 1992.
Tierney R.J., Sreven N., Young L.S., and Rickinson A.B., J Virol 68, 7374-7385, 1994.
Sugiura M., Imai S., Tokunaga M., Koizumi S., Uchizawa M., Okamoto K., and Osato T., Br J Cancer 74, 625-631, 1996.
Takeuchi H., Kobayashi R., Hasegawa M., and Hirai K., J Virol Methods 58, 81-89, 1996
Tokunaga M., Uemura Y., Tokudome T., Ishidate T., Masuda H., Okazaki E., Kaneko K., Naoe S., Ito M., Okamura A., Shimada A., Sato E., and Charles E.L., Acta Pathol Japonica 43, 574-581, 1993.
Takano Y. and Kato Y., J Pathol 175, 39-44, 1995.
Shousha S. and Luqmani Y.A., J Clin Pathol 47, 695-698, 1994.
Arikawa J., Tokunaga M., Satoh E., Tanaka S., and Charles E.L., Pathol Int 47, 360-367, 1997.
Imai S., Koizumi S., Sugiura M., Tokunaga M., Uemura Y., Yamamoto N., Tanaka S., Sato E., and Osato T., Proc Natl Acad Sci USA 91, 9131-9135, 1994.
Shibata D. and Weiss L.M., Am J Pathol 140, 769-774, 1992.
Tokunaga M., Land C.E., Uemura Y., Tokudome T., Tanaka S., and Sato E., Am J Pathol 143, 1250-1254, 1993.
Nakamura S., Ueki T., Yao T., Ueyama T., and Masazumi T., Cancer 73, 2239-2249, 1994.
Fukayama M., Hayashi Y., Iwasaki Y., Chong J., Ooba T., Takizawa T., Koike M., Mizutani S., Miyaki M., and Hirai K., Lab Invest 71, 73-81, 1994.
Iwasaki Y., Chon J., Hayashi Y., Ikeno R., Arai K., Kitamura M., Koike M., Hirai K., and Fukayama M., J Virol 72, 8321-8326, 1998.
Fruehling S. and Longnecker R., Virology 235, 241-251, 1997.
Longnecker R. and Kieff E., J Virol 64, 2319-2326, 1990.
Burkhardt A., Bolen J.B., Kieff E., and Longnacker R., J Virol 66, 5161-5167, 1992.
Longnacker R., Druker B., Roberts T.M., and Kieff E., J Virol 65, 3681-3692, 1991.
Fruehling S., Swart R., Dolwick K.M., Kremmer E., and Longnecker R., J Virol 72, 7796-7806, 1998.
Brielmeier M., Mautner J., Laux G., and Hammerschmidt W., J Gen Virol 77, 2807-2818, 1996.
Longnecker R., Miller C.L., Tomkinson B., Miao X., and Kieff E., J Virol 67, 5068-5074, 1993.
Fruehling S., Caldwell R., and Longnecker R., Epstein-Barr Virus Report 4, 151-159, 1997.
Lee S.P., Tierney R.J., Thomas W.A., Brooks J.M., and Rickinson A.B., J Immunol 158, 3325-3334, 1994.
Bryden H., Mackenzie J., Andrew L., Alexander F.E., Angus B., Krajewski A.S., Armstrong A.A., Gray D., Cartwright R.A., Kane E., Wright D.H., Taylor P., and Jarrett R.F., Int J Cancer 72, 614-618, 1997.
Lee S.P., Thomas W.A., Murray R.J., Khanim F., Kaur S., Young L.S., Rowe M., Kurilla M., and Rickinson A.B., J Virol 67, 7428-7435, 1993.
Bear R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J., Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C., Tuffnall P.S., and Barrell B.G., Nature 310, 207-211, 1984.
Japanese Research Society for Gastric cancer, Jpn J Surg 12, 64-89, 1993 (in Japan).
Smith P.R. and Griffin B.E., J Virol 66, 706-714, 1992.
Hironaka T., Nagasaki M., Morikawa S., and Hirai K., J Virol Methods 44, 141-154, 1993.
Miller W.E., Edwards R.H., Walling D.M., and Raab-Traub N., J Gen Virol 75, 2729-2740, 1994.
Sample J., Young L., Martin B., Chatman T., Kieff E., Rickinson A., and Kieff E., J Virol 64, 4084-4092, 1990.
Busson P., Edwards R.H., Tursz T., and Raab-Traub N., J Gen Virol 76, 139-145, 1995.
Apolloni A., Moss D., Stumm R., Burrows S., Suhrbier A., Misko I., Schmidt C., and Sculley T., Eur J Immunol 22, 183-189, 1992.
Moritani S., Kushima R., Sugihara H., and Hattori T., J Cancer Res Clin Oncol 122, 750-756, 1996.
Franken M., Annis B., Ali A.N., and Wang F., J Virol 69, 8011-8019, 1995.
Hao Q., Saida T., Kawakami H., Mine H., Maruya E., Inoko H., and Saji H., Hum Immunol 35, 116-124, 1992.
Sugiyama Y., Kudoh S., Maeda H., Suzaki H., and Takako F., Am Rev Respir Dis 141, 1459-1462, 1990.
Fennewald S., Van Santen V., and Kieff E., J Virol 51, 411-419, 1984.
Hatfull G., Bankier A., Barrell B., and Farrell P., Virol 164, 334-340, 1988.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tanaka, M., Kawaguchi, Y., Yokofujita, J. et al. Sequence Variations of Epstein-Barr Virus LMP2A Gene in Gastric Carcinoma in Japan. Virus Genes 19, 103–111 (1999). https://doi.org/10.1023/A:1008171006400
Issue Date:
DOI: https://doi.org/10.1023/A:1008171006400