Hepatitis Viruses

Ongoing projects

• 1. Development of lateral flow based rapid immunochromatographic point-of-care assays for diagnosis of viral diseases of public health importance (Component A: Hepatitis A and E diagnosis)
• 2. Providing diagnosis for hepatitis viruses and support during outbreak investigation
• 3. Cellular antiviral responses against hepatitis B virus
• 4. Study of involvement of host factors in chikungunya virus infection
• 5. Identification, characterization and validation of neutralizing monoclonal antibodies (MAbs) against hepatitis E Virus
• 6. Study of the involvement of host factors in hepatitis E virus infection during pregnancy
• 7. Computational drug repurposing approaches for the development of therapeutics against hepatitis E virus
• 8. Study of anti-chikungunya virus specific antibody dependent cellular cytotoxicity Immune response
• 9. Hepatitis E virus replication and cellular autophagy
• 10. Assessment of risk factors for the development of cardiovascular disease (CVD) in patients with active HCV infection
• 11. Identification of specific cell signatures using single-cell RNA-seq and phenotypic analyses in patients with SARS-COVID-19 infection
• 12. Use of SARS-CoV-2 spike and nucleocapsid proteins in assessment of antibody response in infected/ recovered individuals
• 13. Complete transcriptome analysis of cells in throat/nasal swabs of COVID-19 patients in India
• 14. Assessment of the role of host immune response in COVID-19 infection

Significant Research Findings/Contributions:

• Genomic characterization of viruses, molecular epidemiology and evolution
• Identification of the causative agent of hepatitis E, hepatitis E virus (HEV) as cause of majority waterborne NANB epidemics, starting from the historic 1955 epidemic in New Delhi
• Molecular epidemiology based on phylogenetic analyses of HAV, HBV, HCV and HEV
• Full genome sequencing of hepatitis viruses, viral evolution
• Identification of viral mutants and their significance in pathogenesis
• Documentation of the new 9th HBV genotype “I” in India
• Identification of a new subgenotype of HCV, 3i accepted by ICTV (HCV)
• Prevalence of HEV genotype-1 in humans and genotype-4 in pigs in India
• First full genome sequences of HEV genotype 1 (human) and genotype 4 (swine) viruses from India
• 1Characterization of simian HAV (genotype V) recovered from a captive rhesus monkey
• Predominance of genotype IIIA of HAV since 1981 in India and estimates of evolution of this virus
• Nipah virus: Investigated intrafamilial outbreak of suspected NIPAH virus, confirmed etiology carried out full genome sequencing from an autopsied lung sample.
• Chikungunya: Documentation of shift of genotype from Asian to African. Genomic analysis of the viruses isolated during 1963-2009
• Detection of a newly discovered KIs virus in India

Epidemiology, virus transmission and animal studies

• Determination of prevalence of HAV, HEV, HBV and HCV by age-stratified serosurveys in urban and rural populations
• Periodic serosurveys leading to important information on changing epidemiology and prediction of future epidemics of hepatitis A in India
• Serosurveys in populations at-risk and suggestion to the Govt. for vaccination
• HGV and TTV were shown to be of no significance in causing liver diseases
• Detection of anti-HEV antibodies in various animal sera suggesting possible zoonotic transmission of the virus
• Possibility of transfusion-associated hepatitis E, presence of virus seen in blood units from donors
• Experimental HEV infection in rhesus monkeys to study natural course of the disease and possible of utility of vaccine
• Beneficial effect of human Immunoglobulins in HEV infections among pregnant women
• Anti-HEV antibodies persist for 30 years post HEV infection in hepatitis E recovered individuals
• Screening of blood donors for HEV prevalence & occult HBV infection demonstrated the need to consider cost-effective evaluation for pooled HEV RNA testing in blood banks in HEV endemic regions & also pooled HBV DNA screening

Development of diagnostic tests

Serological:

• Development of ELISA for anti-HBs detection
• Development of ELISAs for IgM and IgG-anti-HAV
• Development of ELISAs for IgM and IgG-anti-HE
• Development of ELISA for IgG-anti-CHP antibodies
• Development of ELISA IgG-anti-CHIK antibodies
• Development of lateral flow based immunochromatographic point-of-care HEV IgM Rapid Test

Molecular:

• Diagnostic PCR assays for all hepatitis viruses (HAV, HBV, HCV, HEV, HGV & TTV)
• Genotyping and phylogenetic analyses based on partial and full genome sequences of hepatitis viruses
• Taqman-chemistry based assays for the detection and quantitation of HAV, HBV, HCV, HEV and Chandipura and chikungunya viruses were standardized and used for diagnosis / research projects
• Development of a method for virus concentration from water samples and detection by RT-PCR

Development of candidate vaccines

• Hepatitis E: successful pre-clinical studies in rhesus monkeys
• Combination vaccine (HBV+HEV): Immunogenicity studies in mice and pre-clinical study in rhesus monkeys
• Hepatitis C vaccine: Recombinant proteins based candidate vaccines: tested in mice
• Chandipura vaccine: Highly efficacious recombinant glycoprotein based vaccine, G protein alone or in combination with commercially available DPT vaccine
• Chikungunya: Evaluation of recombinant E2 protein-based and whole-virus inactivated candidate vaccines both were highly immunogenic
• Pandemic and Seasonal Influenza: inter-clade protection seen with Mw-adjuvanted recombinant HA, NP proteins, and M2e peptide combination vaccine when tested in mice

Molecular virology

• Deciphering role of HEV ORF1 encoded non-structural proteins replicase, helicase, protease and macrodomain in HEV replication
• Influence of non-structural proteins on the host specificity of hepatitis E viruses
• Development of infectious clones of HEV, HBV and HCV and utilization in studying molecular events during virus replication, host-virus interactions and antiviral testing
• Development of HAV VLPs and utility in diagnostic ELISA
• Importance of cellular innate antiviral responses during HEV infection
• Involvement of miRNA 122 in HEV replication
• Induction of cellular autophagy by HEV for efficient replication
• Anti-apoptotic role of HBeAg protein of HBV in preventing cell damage during virus infection

Pathogenesis:

• 1.Understanding pathogenesis of HEV
• 2.Establishment of the role of complement system in the defense mechanism of Chandipura infection
• 3.Pivotal anti viral role of TNF-α against Chandipura virus. Demonstration of putative role of NK cells in chikungunya infection

Biomarker studies

• Pivotal role of CCL4 and NKT cells in limiting HBV infections.
• IL-1α & sIL-2Rα as markers of inflammation in hepatitis E
• Protective role of T regulatory cells (Tregs) in self-limiting hepatitis E
• Role of TGF-β1 as a possible supplement for boosting Treg response and protection from fatal outcome in patients with fulminant hepatitis E.
• Importance of epitopes presented by HLA-DRB1* 11 towards induction of protective immune response in hepatitis E, hepatitis C and chikungunya infections
• Identification of memory B cell response as co-correlates of protection against HEV infection
• Higher levels of NKp44: marker of recent chikungunya infection

Services:

• Hepatitis Outbreaks: Investigated over 150 epidemics of viral hepatitis, provided diagnosis and suggested control measures to the local health authorities
• Drug Controller of India: Blood products imported from other countries are sent to NIV for testing for HBsAg and HCV RNA. Reports are provided in 2-3 days.
• Diagnostic services: Serological and molecular testing for the diagnosis of acute viral hepatitis, determination of viral load, genotype
• Water testing: Water samples are processed for concentration of virus and detected by molecular testing