Related Experiment Video
Updated: Jul 20, 2026
09:35
Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
Evolution of multi-drug resistant hepatitis B virus during sequential therapy
Hyung Joon Yim1, Munira Hussain, Ying Liu
1Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109-0362, USA.
Hepatology (Baltimore, Md.)
|August 31, 2006
Summary
Mutations conferring resistance to multiple antiviral drugs in hepatitis B virus (HBV) co-locate on the same viral genome. This finding suggests current combination therapies may be insufficient for treating multi-drug resistant HBV infections.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Sequential antiviral therapy for hepatitis B virus (HBV) can lead to multi-drug resistance.
- In vitro studies indicate resistance mutations can affect drug sensitivity.
- The in vivo co-location and evolution of these mutations remain unclear.
Purpose of the Study:
- To determine if mutations conferring resistance to multiple antiviral agents co-locate on the same HBV genome in vivo.
- To describe the evolutionary patterns of these multi-drug resistance mutations.
Main Methods:
- Sera from six patients with multi-drug resistant HBV mutations were analyzed.
- Nested polymerase chain reaction (PCR) and cloning were used for mutation analysis.
- Direct sequencing and clonal analysis of serial samples were performed.
Main Results:
- Analysis of 215 clones revealed 85% had mutations to both therapies on the same genome.
- 31 clones exhibited only lamivudine-resistant mutants.
- Serial sample analysis showed a progression towards multi-drug resistant mutations.
Conclusions:
- Mutations conferring resistance to multiple antiviral agents co-locate on the same HBV genome.
- Combination therapy targeting individual drug resistance may be inadequate for suppressing multi-drug resistant HBV.
- De novo combination therapy could potentially prevent the emergence of multi-drug resistant mutants.
Related Concept Videos
01:10Retrovirus Life Cycles
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
01:25Hepatitis
Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
00:36Viral Mutations
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
01:28Viral Hepatitis I: Introduction
Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...
01:28Pulmonary Tuberculosis V
Medical management of tuberculosis (TB) patients involves a comprehensive approach that includes diagnosis, treatment, and monitoring. The specific strategies can vary depending on the type of tuberculosis (latent or active), the patient's overall health status, and other considerations.
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the progression...
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the progression...
01:24Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...