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Journal of Virology, July 1999, p. 5767-5776, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

La Autoantigen Specifically Recognizes a Predicted Stem-Loop in Hepatitis B Virus RNAdagger

Tilman Heise,Dagger Luca G. Guidotti, and Francis V. Chisari*

Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037

Received 1 February 1999/Accepted 14 April 1999

We recently identified three nuclear proteins (p45, p39, and p26) that bind to a 91-nucleotide (nt) RNA element between nt 1243 and 1333 in hepatitis B virus (HBV) RNA, and we showed that these proteins and HBV RNA are regulated coordinately by gamma interferon and tumor necrosis factor alpha. Purification and sequence analysis of tryptic peptides obtained from p39 revealed sequence homology to the mouse La protein. Immunoprecipitation experiments showed that p45, p39, and p26 were recognized by anti-La-specific antiserum, indicating that p45 is the full-length La protein and that p39 and p26 are likely to be proteolytic La cleavage products. Furthermore, in competition experiments we found that all three La proteins bind, in a phosphorylation-dependent manner, to the same predicted stem-loop structure located between nt 1275 and 1291 of HBV, with Kds of approximately 1.0 nM. Collectively, these results support the notion that the La protein may contribute to HBV RNA stability, constitutively and in response to inflammatory cytokines.

* Corresponding author. Mailing address: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8228. Fax: (619) 784-2160. E-mail: fchisari{at}scripps.edu.

dagger Paper no. 11631-MEM from The Scripps Research Institute.

Dagger Present address: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, D-20251 Hamburg, Germany.

Journal of Virology, July 1999, p. 5767-5776, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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