scholarly journals In Vitro Systems for Studying Different Genotypes/Sub-Genotypes of Hepatitis B Virus: Strengths and Limitations

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 353 ◽  
Author(s):  
Constance N. Wose Kinge ◽  
Nimisha H. Bhoola ◽  
Anna Kramvis
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
In Vitro Model ◽  
Antiviral Agents ◽  
Model Systems ◽  
Effective Vaccine ◽  
B Virus ◽  
In Vitro Systems ◽  
Vitro Model

Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geographical distributions and prevalence, which have different natural histories of infection, clinical manifestation, and response to current antiviral agents. Here, we review various in vitro systems used to study the molecular biology of the different (sub)genotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations. Despite the advances made, no system is ideal for pan-genotypic HBV research or drug development and therefore further improvement is required. It is necessary to establish a centralized repository of HBV-related generated materials, which are readily accessible to HBV researchers, with international collaboration toward advancement and development of in vitro model systems for testing new HBV antivirals to ensure their pan-genotypic and/or customized activity.

scholarly journals Primary Tupaia Javanica Hepatocyte Culture as an In Vitro Model for Human Hepatitis B Virus Infection

2022 ◽  
Vol 22 (3) ◽  
pp. 203-209
Author(s):  
Kemal Fariz Kalista ◽  
Maryati Surya ◽  
Silmi Mariya ◽  
Diah Iskandriati ◽  
Irsan Hasan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
In Vitro Model ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Primate Research ◽  
Qualitative And Quantitative ◽  
B Virus ◽  
Vitro Model

Background: Hepatitis B virus (HBV) infection is still one of the biggest health problems in the world, which could lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Treatment for HBV infection has not yet achieved a functional cure. More studies are needed to investigate human HBV (HuHBV), but the scarcity of animal models for HuHBV infection became a barrier. Recently, many studies have shown that Tupaia are suitable for the study of HuHBV. The purpose of this study was to develop a primary tupaia hepatocyte (PTH) culture from T. javanica, a species of Tupaia found in Indonesia, and to prove that HuHBV can replicate in the PTH.Method: In vitro experimental study using PTH isolated from five wild adult T. javanica in Primate Research Center, IPB University. HuHBV was taken from humans with HBsAg and HBV-DNA (+). PTH cells then were infected with HuHBV after reaching 80% confluence. Observation on PTH cells was done everyday for 20 days. Qualitative and quantitative HBsAg were measured using a CMIA while HBV-DNA and cccDNA were measured by RT-PCR.Results: A cytopathic effect was seen on day post infection (DPI)-16. HBsAg and HBV-DNA were detected from DPI-2 until DPI-18, with HBV-DNA level peaked on DPI-12. cccDNA concentration was fluctuating from DPI-2 until DPI-20 with highest level on DPI-16.Conclusion: HuHBV could infect and replicate in PTH from T. javanica can be infected with HuHBV and HuHBV can replicate in the PTH from T. javanica.

scholarly journals Polo-like kinase 1 inhibition suppresses hepatitis B virus X protein-induced transformation in an in vitro model of liver cancer progression

Hepatology ◽  
2009 ◽  
Vol 50 (2) ◽  
pp. 414-423 ◽  
Author(s):  
Leo L. Studach ◽  
Lova Rakotomalala ◽  
Wen-Horng Wang ◽  
Ronald L. Hullinger ◽  
Stefano Cairo ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Cancer Progression ◽  
In Vitro Model ◽  
X Protein ◽  
B Virus ◽  
Vitro Model

Review Hepatitis B Virus Resistance to Lamivudine and its Clinical Implications

2002 ◽  
Vol 13 (3) ◽  
pp. 143-155 ◽  
Author(s):  
Xuefeng Liu ◽  
Raymond F Schinazi
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Treatment ◽  
Antiviral Agents ◽  
Lamivudine Therapy ◽  
Combination Strategy ◽  
B Virus ◽  
Ymdd Motif

Lamivudine is the first orally available drug approved for treatment of chronic hepatitis B, but hepatitis B virus (HBV) resistance to lamivudine appears to be a sine qua non in the therapy of HBV. The mutations at the FLLA and YMDD motif in the domains B and C of HBV polymerase contribute to this resistance. These mutations are found at codon (or AA) rtL180M and rtM204V/I in the reverse transcriptase (RT) domain of the HBV polymerase for all genotypes according to a new standardized RT domain numbering system. The resistant HBV may be less replication-competent in vitro and in vivo, and it is rarely associated with markedly increased HBV replication or liver injury. Therefore, certain physicians favour continuing lamivudine therapy even after emergence of HBV resistance with the expectation of maintaining lower-than baseline HBV DNA, alanine aminotransferase, and histological improvement, and avoiding reversion to wild-type HBV until additional antiviral strategies are developed. Ultimately, once several antiviral agents are approved, combination strategy is likely to be incorporated in antiviral treatment for chronic HBV to suppress, prevent or minimize the emergence of resistant virus.

In Vitro Alternatives for Ocular Safety Testing: An Outline of Assays and Possible Future Developments

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 117-128
Author(s):  
David K. Wilcox ◽  
Leon H. Bruner
Keyword(s):  
Safety Assessment ◽  
In Vitro Model ◽  
Model Systems ◽  
In Vitro Tests ◽  
Safety Testing ◽  
In Vitro Systems ◽  
Vitro Model ◽  
Development And Validation ◽  
Ocular Safety

An increasing number of in vitro tests are being proposed as alternatives for animals in ocular safety testing. These in vitro systems use a variety of approaches and measure a broad range of endpoints, including cellular cytotoxicity and metabolism. We will briefly review the development and validation of these model systems. Several tests appear promising, and may prove useful as adjuncts in our current ocular safety assessment schemes. We will also discuss how these tests can most rapidly be brought to use in ocular safety assessment, and where efforts should be directed to develop more-highly predictive in vitro model systems for the future.

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