Sibnarayan Datta

Publications (29) View all

• Article: Molecular Biology of the Hepatitis B Virus for Clinicians

  Sibnarayan Datta, Soumya Chatterjee, Vijay Veer, Runu Chakravarty
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  ABSTRACT: Hepatitis B virus (HBV) infection is one of the major global health problems, especially in economically under-developed or developing countries. HBV infection can lead to a number of clinical outcomes including chronic infection, cirrhosis and liver cancer. It ranks among the top 10 causes of death, being responsible for around 1 million deaths every year. Despite the availability of a highly efficient vaccine and potent antiviral agents, HBV infection still remains a significant clinical problem, particularly in those high endemicity areas where vaccination of large populations has not been possible due to economic reasons. Although HBV is among the smallest viruses in terms of virion and genome size, it has numerous unique features that make it completely distinct from other DNA viruses. It has a partially double stranded DNA with highly complex genome organization, life cycle and natural history. Remarkably distinct from other DNA viruses, it uses an RNA intermediate called pregenomic RNA (pgRNA) and reverse transcriptase for its genome replication. Genome replication is accomplished by a complex mechanism of primer shifting facilitated by direct repeat sequences encoded in the genome. Further, the genome has evolved in such a manner that every single nucleotide of the genome is used for either coding viral proteins or used as regulatory regions or both. Moreover, it utilizes internal in-frame translation initiation codons, as well as different reading frames from the same RNA to generate different proteins with diverse functions. HBV also shows considerable genetic variability which has been related with clinical outcomes, replication potential, therapeutic response etc. This review aims at reviewing fundamental events of the viral life cycle including viral replication, transcription and translation, from the molecular standpoint, as well as, highlights the clinical relevance of genetic variability of HBV.
  Journal of Clinical and Experimental Hepatology. 12/2012; 2(2):353.
• Article: Influence of HIV-associated degree of immune suppression on molecular heterogeneity of hepatitis B virus among HIV co-infected patients.

  Ananya Pal, Rajesh Panigrahi, Avik Biswas, Sibnarayan Datta, Neelakshi Sarkar, Subhashish Kamal Guha, Bibhuti Saha, Arup Banerjee, Sekhar Chakrabarti, Runu Chakravarty
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  ABSTRACT: We have investigated the molecular diversity of Hepatitis B virus (HBV) among the HIV co-infected patients from eastern-India. HBsAg/HBV-DNA positive subjects (n=73) from 874 HIV-infected patients were analyzed by sequencing followed by genetic diversity quantification. HBV/genotype-D and HBV/sugenotype-D2 were predominant. HBV/D2 isolates from patients with low CD4 count manifested significantly lower non-synonymous substitutions (p<0.0001) and Shannon entropy (p=0.0006) in their surface and polymerase gene in comparison to those from moderately increased CD4 count. ART-induced immune-reconstitution therefore might raise non-synonymous immune/therapy escape substitutions among these HBV/D2 isolates. Decreased genetic diversity and increased viral load in the HBV/D2 isolates might facilitate the maintenance of their wild type characteristics in the low CD4 count, leading to its increased prevalence in this group. Interestingly, genetic diversity in HBV/A1, the next common subgenotype, was modified in the opposite manner. Together our results underscore the need for proper HBV molecular monitoring in HIV co-infection.
  Virology 12/2012; · 3.35 Impact Factor
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  Available from: Deep Dutta

  Article: Variations in the functional domain of basal core promoter of hepatitis B virus among Eastern Indian patients with prevalence of genotypes A, C, and D among the same ethnic population.

  Avik Biswas, Arup Banerjee, Partha Kumar Chandra, Sibnarayan Datta, Rajesh Panigrahi, Deep Dutta, Binay Krishna De, Manisha Pal, Subhashish Kamal Guha, Sekhar Chakrabarti, Runu Chakravarty
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  ABSTRACT: Mutations in the basal core promoter (BCP) and precore (PC) regions are associated with persistent and intermittently high hepatitis B virus (HBV) replication in several patients. The variability in the functional domains of BCP and PC region of HBV and their association with disease progression and clinical outcome were assessed in Eastern India, an unique region where three HBV genotypes, A, D, and C are prevalent among the same ethnic group. PCR amplification and direct sequencing of BCP and PC region was done on sera obtained from 130 HBsAg positive subjects with different clinical presentations. Associations of the apparent risk factors with clinical advancement were evaluated by statistical methods including multiple logistic regression analyses (MLR). HBV genotype A was present in 33.08%, C in 25.38%, and D in 41.54% cases. Genotypes A and C were associated with higher rate of T1762/A1764 mutations than the most predominant genotype D. HBeAg negative state was associated with considerably higher rate of C1753 mutation. T1762/A1764 along with C1753 was common among cirrhosis and T1762/A1764 without C1753 was frequent among chronic liver disease cases. No significant association was found between A1896 point mutation and clinical status. Multivariate analysis revealed that T1762/A1764 double mutation, HBV/A, age ≥25 years, C1753 and A1899 were critical factors for clinical advancement while age ≥25 years and C1753 as significant predictor for cirrhosis in comparison with chronic liver disease. In conclusion, the analysis of the BCP variability may help in monitoring the progression towards advanced liver disease in Eastern Indian patients.
  Journal of Medical Virology 02/2011; 83(2):253-60. · 2.82 Impact Factor
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  Available from: Sibnarayan Datta

  Article: Mechanism of HCV's resistance to IFN-α in cell culture involves expression of functional IFN-α receptor 1.

  Sibnarayan Datta, Sidhartha Hazari, Partha K Chandra, Maria Samara, Bret Poat, Feyza Gunduz, William C Wimley, Hansjorg Hauser, Mario Koster, Christophe Lamaze, Luis A Balart, Robert F Garry, Srikanta Dash
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  ABSTRACT: The mechanisms underlying the Hepatitis C virus (HCV) resistance to interferon alpha (IFN-α) are not fully understood. We used IFN-α resistant HCV replicon cell lines and an infectious HCV cell culture system to elucidate the mechanisms of IFN-α resistance in cell culture. The IFN-α resistance mechanism of the replicon cells were addressed by a complementation study that utilized the full-length plasmid clones of IFN-α receptor 1 (IFNAR1), IFN-α receptor 2 (IFNAR2), Jak1, Tyk2, Stat1, Stat2 and the ISRE-luciferase reporter plasmid. We demonstrated that the expression of the full-length IFNAR1 clone alone restored the defective Jak-Stat signaling as well as Stat1, Stat2 and Stat3 phosphorylation, nuclear translocation and antiviral response against HCV in all IFN-α resistant cell lines (R-15, R-17 and R-24) used in this study. Moreover RT-PCR, Southern blotting and DNA sequence analysis revealed that the cells from both R-15 and R-24 series of IFN-α resistant cells have 58 amino acid deletions in the extracellular sub domain 1 (SD1) of IFNAR1. In addition, cells from the R-17 series have 50 amino acids deletion in the sub domain 4 (SD4) of IFNAR1 protein leading to impaired activation of Tyk2 kinase. Using an infectious HCV cell culture model we show here that viral replication in the infected Huh-7 cells is relatively resistant to exogenous IFN-α. HCV infection itself induces defective Jak-Stat signaling and impairs Stat1 and Stat2 phosphorylation by down regulation of the cell surface expression of IFNAR1 through the endoplasmic reticulum (ER) stress mechanisms. The results of this study suggest that expression of cell surface IFNAR1 is critical for the response of HCV to exogenous IFN-α.
  Virology Journal 01/2011; 8:351. · 2.34 Impact Factor
• Article: Genetic linkage of hepatitis B virus in peripheral blood leukocytes provides evidence for contamination.

  Chloe L Thio, Stuart C Ray, Sibnarayan Datta, Rajesh Panigrahi, Avik Biswas, Runu Chakravarty
  Journal of Virology 02/2010; 84(4):2184-6. · 5.40 Impact Factor