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Antimicrobial Agents and Chemotherapy, July 2005, p. 2618-2624, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2618-2624.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Emergence of a Novel Mutation in the FLLA Region of Hepatitis B Virus during Lamivudine Therapy

S. Balakrishna Pai,1 A. Mithat Bozdayi,3,4 Rekha B. Pai,2 Tolunay Beker,2 Mustafa Sarioglu,4 Ahmet R. Turkyilmaz,3 Jason Grier,1 Cihan Yurdaydin,3,4 and Raymond F. Schinazi1,2*

Veterans Affairs Medical Center, Decatur, Georgia,1 Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia,2 Institute of Hepatology, Ankara University, Ankara, Turkey,3 Department of Gastroenterology, School of Medicine, Ankara University, Ankara, Turkey4

Received 29 October 2004/ Returned for modification 28 December 2004/ Accepted 15 March 2005

The emergence of resistance to lamivudine has been one of the major stumbling blocks to successful treatment and control of hepatitis B virus (HBV) infections. The major mechanism of resistance has been attributed to the alteration in the YMDD motif of the HBV polymerase due to an amino acid change of rtM204 to V/I and an accompanying rtL180M conversion. A novel mutation pattern in a patient having clinical breakthrough under lamivudine therapy was discovered. The mutant had a rtL180C/M204I genotype and was detected after 2 years of therapy with lamivudine. To characterize this novel variant, site-directed mutagenesis was performed using a vector construct containing the HBV genome. Transient transfection studies in human hepatoma cells with HBV carrying the new mutant demonstrated that the rtL180C/M204I mutant was resistant to lamivudine up to 10 µM. The resistance profile was comparable to that of the previously reported rtL180 M/M204I-containing virus. These observations were further confirmed by generation of stable cultures transfected with the mutant virus.

* Corresponding author. Mailing address: Veterans Affairs Medical Center, Medical Research 151 H, 1670 Clairmont Road, Decatur, GA 30033. Phone: 404-728-7711. Fax: 404-728-7726. E-mail: rschina{at}emory.edu.

Antimicrobial Agents and Chemotherapy, July 2005, p. 2618-2624, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2618-2624.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yatsuji, H., Noguchi, C., Hiraga, N., Mori, N., Tsuge, M., Imamura, M., Takahashi, S., Iwao, E., Fujimoto, Y., Ochi, H., Abe, H., Maekawa, T., Tateno, C., Yoshizato, K., Suzuki, F., Kumada, H., Chayama, K. (2006). Emergence of a Novel Lamivudine-Resistant Hepatitis B Virus Variant with a Substitution Outside the YMDD Motif. Antimicrob. Agents Chemother. 50: 3867-3874 [Abstract] [Full Text]  


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