Related Experiment Video

Updated: Mar 31, 2026

Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells
11:20

Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells

Published on: June 3, 2012

13.5K

Battle between influenza A virus and a newly identified antiviral activity of the PARP-containing ZAPL protein

Chien-Hung Liu1, Ligang Zhou1, Guifang Chen1

  • 1Department of Molecular Biosciences, Center for Infectious Disease, Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712.

Proceedings of the National Academy of Sciences of the United States of America
|October 28, 2015
PubMed

Insights

Zinc finger antiviral protein (ZAPL) targets influenza A virus polymerase proteins PB2 and PA for degradation. Viral protein PB1 interferes, reducing ZAPL

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Zinc finger antiviral protein (ZAPL), also known as PARP-13.1, previously demonstrated antiviral functions through mRNA binding.
  • Influenza A virus (IAV) poses a significant global health threat, necessitating novel antiviral strategies.

Purpose of the Study:

  • To elucidate the mechanism of ZAPL's antiviral activity against influenza A virus.
  • To identify host-pathogen interactions that regulate ZAPL-mediated inhibition of IAV replication.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Western blotting to assess protein levels and ubiquitination.
  • Proteasomal degradation assays.
  • Analysis of ZAPL's interaction with viral polymerase subunits (PB1, PB2, PA).

Main Results:

  • ZAPL inhibits influenza A virus replication through its C-terminal PARP domain, distinct from its previously known N-terminal antiviral mechanism.
  • ZAPL's PARP domain binds viral PB2 and PA proteins, leading to their poly(ADP-ribosylation), ubiquitination, and subsequent proteasomal degradation.
  • The viral PB1 polymerase protein counteracts ZAPL activity by binding near the PARP domain, preventing PB2 and PA dissociation and degradation.
  • IAV replication is only moderately inhibited by ZAPL due to this counteraction by PB1.

Conclusions:

  • A novel ZAPL-mediated antiviral pathway targeting IAV polymerase proteins PB2 and PA has been identified.
  • Influenza A virus has evolved a mechanism involving PB1 to evade ZAPL-mediated degradation.
  • The PB1-ZAPL interface represents a potential therapeutic target for developing new antiviral drugs against influenza A virus.
Keywords:
ZAPL PARP domaininfluenza A virus polymerase protein subunitspoly(ADP-ribosylation)proteasomal degradationubiquitination

More Related Videos

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.9K
Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit22:10

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit

Published on: June 28, 2013

13.8K

Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.9K
Influenza01:27

Influenza

Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
37
Viral Recombination00:57

Viral Recombination

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.
25.6K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.6K
The Antiviral System of Bacteria and Archaea: CRISPR01:23

The Antiviral System of Bacteria and Archaea: CRISPR

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this...
987
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

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...
24