This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, S.-Y.
Right arrow Articles by Sheen, I-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, S.-Y.
Right arrow Articles by Sheen, I-J.

 Previous Article  |  Next Article 

Journal of Virology, May 2007, p. 4438-4444, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02847-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Positive Selection of Hepatitis Delta Antigen in Chronic Hepatitis D Patients{triangledown}

Shen-Yung Wang,1,5 Jaw-Ching Wu,1,3* Tzen-Yuh Chiang,6 Yi-Hsiang Huang,2,3 Chien-Wei Su,2,4 and I-Jane Sheen2

Department of Medical Research and Education,1 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei,2 Institute of Clinical Medicine,3 Faculty of Internal Medicine, National Yang-Ming University School of Medicine, Taipei,4 Division of Gastroenterology, Department of Medicine, Mackay Memorial Hospital, Taipei,5 Department of Life Sciences, National Cheng-Kung University, Tainan, Taiwan6

Received 22 December 2006/ Accepted 5 February 2007

Liver disease may become ameliorated in some patients with chronic hepatitis D virus (HDV) infection. We present here a study based on longitudinal sampling to investigate the viral dynamics in chronic HDV infection. We examined the HDV variants from different time points, especially those before and after the elevation of serum aminotransferase levels. The datasets from each patient were tested for positive selection by using maximum-likelihood methods with heterogeneous selective pressures along the nucleotide sequence. An average of 4.9%, ranging from 3.1 to 6.8%, of the entire delta antigen sites was regulated by a diversifying selection. Most of the positively selected sites were associated with immunogenic domains. Likelihood ratio tests revealed a significant fitness of positive selection over neutrality of the hepatitis delta antigen gene in all patients. We further adapted a neural network method to predict potential cytotoxic T ligand epitopes. Among the HLA-A*0201 cytotoxic T ligand epitopes, three consistent epitopes across all three genotypes were identified: amino acids (aa) 43 to 51, 50 to 58, and 114 to 122. Three patients (60%) had sites evolving under positive selection in the epitope from aa 43 to 51, and four patients (80%) had sites evolving under positive selection in the epitope from aa 114 to 122. The discovery of immunogenic epitopes, especially cytotoxic-T-lymphocyte ligands, associated with chronic HDV infection may be crucial for further development of novel treatments or designs in vaccine for HDV superinfection.

* Corresponding author. Mailing address: Department of Medical Research and Education, Taipei Veterans General Hospital, 201, Shih-Pai Road, Sec. 2, Taipei 11217, Taiwan. Phone: 886-2-28712121, ext. 3218. Fax: 886-2-28745074. E-mail: jcwu{at}vghtpe.gov.tw

{triangledown} Published ahead of print on 14 February 2007.

Journal of Virology, May 2007, p. 4438-4444, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02847-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»