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Journal of Virology, October 2009, p. 9983-9992, Vol. 83, No. 19
0022-538X/09/$08.00+0 doi:10.1128/JVI.01905-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Genetic Characterization of Hepatitis B Virus in Peripheral Blood Leukocytes: Evidence for Selection and Compartmentalization of Viral Variants with the Immune Escape G145R Mutation
,
Sibnarayan Datta,1,
Rajesh Panigrahi,1,
Avik Biswas,1,
Partha K. Chandra,1,
Arup Banerjee,1,¶
Pradip K. Mahapatra,2
Chinmoy K. Panda,3
Shekhar Chakrabarti,1,4
Sujit K. Bhattacharya,1,4
Kuntal Biswas,5 and
Runu Chakravarty1*
ICMR Virus Unit, Kolkata, India,1 Department of Chemistry, Jadavpur University, Kolkata, India,2 Chittaranjan National Cancer Institute (CNCI), Kolkata, India,3 National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India,4 Medical College and Hospital, Kolkata, India5
Received 10 September 2008/ Accepted 14 April 2009
The compartmentalization of viral variants in distinct host tissues is a frequent event in many viral infections. Although hepatitis B virus (HBV) classically is considered hepatotropic, it has strong lymphotropic properties as well. However, unlike other viruses, molecular evolutionary studies to characterize HBV variants in compartments other than hepatocytes or sera have not been performed. The present work attempted to characterize HBV sequences from the peripheral blood leukocytes (PBL) of a large set of subjects, using advanced molecular biology and computational methods. The results of this study revealed the exclusive compartmentalization of HBV subgenotype Ae/A2-specific sequences with a potent immune escape G145R mutation in the PBL of the majority of the subjects. Interestingly, entirely different HBV genotypes/subgenotypes (C, D, or Aa/A1) were found to predominate in the sera of the same study populations. These results suggest that subgenotype Ae/A2 is selectively archived in the PBL, and the high prevalence of G145R indicates high immune pressure and high evolutionary rates of HBV DNA in the PBL. The results are analogous to available literature on the compartmentalization of other viruses. The present work thus provides evidence in favor of the compartment-specific abundance, evolution, and emergence of the potent immune escape mutant. These findings have important implications in the field of HBV molecular epidemiology, transmission, transfusion medicine, organ transplantation, and vaccination strategies.
* Corresponding author. Mailing address: ICMR Virus Unit, ID & BG Hospital Campus, 57, Dr. Suresh Chandra Banerjee Rd., Pin-700 010, Kolkata, India. Phone: 91 33 23537425. Fax: 91 33 23537424. E-mail: runugc{at}yahoo.co.uk
Published ahead of print on 6 May 2009.
Supplemental material for this article may be found at http://jvi.asm.org/.
These authors contributed equally to this work.
Present address: Tulane University Health Sciences Center, Department of Pathology and Laboratory Medicine, 1430 Tulane Ave. SL-79, New Orleans, LA 70112.
¶ Present address: St. Louis University School of Medicine, Division of Infectious Diseases & Immunology, Edward A. Doisy Research Center, St. Louis, MO 63104.
Journal of Virology, October 2009, p. 9983-9992, Vol. 83, No. 19
0022-538X/09/$08.00+0 doi:10.1128/JVI.01905-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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