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Related Concept Videos

Hepatitis01:25

Hepatitis

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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.
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Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

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Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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Pharmacokinetics: Drug–Food and Drug–Viral Interactions01:26

Pharmacokinetics: Drug–Food and Drug–Viral Interactions

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A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of...
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Viruses with RNA Genomes01:29

Viruses with RNA Genomes

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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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Retroviruses02:33

Retroviruses

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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Viral Recombination00:57

Viral Recombination

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Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
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Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
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The Hepatitis E virus intraviral interactome.

Andreas Osterman1, Thorsten Stellberger2,3, Anna Gebhardt1

  • 1Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany.

Scientific Reports
|October 15, 2015
PubMed
Summary
This summary is machine-generated.

This study maps Hepatitis E virus (HEV) protein interactions, revealing novel connections like RNA-dependent RNA polymerase homodimerization. These findings provide a foundation for understanding HEV replication and developing new antiviral therapies.

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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
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Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Hepatitis E virus (HEV) causes significant liver disease globally.
  • Understanding HEV's replication cycle is hindered by limited cell culture and animal models.
  • Investigating protein-protein interactions (PPIs) is crucial for elucidating viral mechanisms.

Purpose of the Study:

  • To comprehensively map all intraviral protein-protein interactions (PPIs) within HEV.
  • To identify novel interactions and characterize their functional significance in viral replication.
  • To explore potential antiviral targets based on identified HEV protein interactions.

Main Methods:

  • Systematic Yeast two-hybrid (Y2H) screening.
  • Luminescence-based Mammalian Interactome Mapping (LuMPIS) screens.
  • Determination of dissociation constants (Kd) for key interactions.

Main Results:

  • Identified key HEV PPIs consistent with existing structural data.
  • Discovered 20 novel PPIs, including RNA-dependent RNA polymerase (RdRp) homodimerization and papain-like protease self-interaction.
  • Characterized ORF3 interactions with RdRp, methylase, helicase, and papain-like protease, suggesting a regulatory role in replicase complex formation.

Conclusions:

  • The study provides a comprehensive map of HEV intraviral PPIs.
  • Novel interactions, particularly involving ORF3, offer insights into replicase complex assembly and regulation.
  • Identified HEV protein interactions represent promising targets for the development of antiviral drugs.