Antiviral activity of double-stranded RNA-binding protein PACT against influenza A virus mediated via suppression of viral RNA polymerase. 2018

Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.

PACT is a double-stranded RNA-binding protein that has been implicated in host-influenza A virus (IAV) interaction. PACT facilitates the action of RIG-I in the activation of the type I IFN response, which is suppressed by the viral nonstructural protein NS1. PACT is also known to interact with the IAV RNA polymerase subunit PA. Exactly how PACT exerts its antiviral activity during IAV infection remains to be elucidated. In the current study, we demonstrated the interplay between PACT and IAV polymerase. Induction of IFN-β by the IAV RNP complex was most robust when both RIG-I and PACT were expressed. PACT-dependent activation of IFN-β production was suppressed by the IAV polymerase subunits, polymerase acidic protein, polymerase basic protein 1 (PB1), and PB2. PACT associated with PA, PB1, and PB2. Compromising PACT in IAV-infected A549 cells resulted in the augmentation of viral RNA (vRNA) transcription and replication and IFN-β production. Furthermore, vRNA replication was boosted by knockdown of PACT in both A549 cells and IFN-deficient Vero cells. Thus, the antiviral activity of PACT is mediated primarily via its interaction with and inhibition of IAV polymerase. Taken together, our findings reveal a new facet of the host-IAV interaction in which the interplay between PACT and IAV polymerase affects the outcome of viral infection and antiviral response.-Chan, C.-P., Yuen, C.-K., Cheung, P.-H. H., Fung, S.-Y., Lui, P.-Y., Chen, H., Kok, K.-H., Jin, D.-Y. Antiviral activity of double-stranded RNA-binding protein PACT against influenza A virus mediated via suppression of viral RNA polymerase.

UI MeSH Term Description Entries
D009980 Influenza A virus The type species of the genus ALPHAINFLUENZAVIRUS that causes influenza and other diseases in humans and animals. Antigenic variation occurs frequently between strains, allowing classification into subtypes and variants. Transmission is usually by aerosol (human and most non-aquatic hosts) or waterborne (ducks). Infected birds shed the virus in their saliva, nasal secretions, and feces. Alphainfluenzavirus influenzae,Avian Orthomyxovirus Type A,FLUAV,Fowl Plague Virus,Human Influenza A Virus,Influenza Virus Type A,Influenza Viruses Type A,Myxovirus influenzae-A hominis,Myxovirus influenzae-A suis,Myxovirus pestis galli,Orthomyxovirus Type A,Orthomyxovirus Type A, Avian,Orthomyxovirus Type A, Human,Orthomyxovirus Type A, Porcine,Pestis galli Myxovirus,Fowl Plague Viruses,Influenza A viruses,Myxovirus influenzae A hominis,Myxovirus influenzae A suis,Myxovirus, Pestis galli,Myxoviruses, Pestis galli,Pestis galli Myxoviruses,Plague Virus, Fowl,Virus, Fowl Plague
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072283 A549 Cells An immortalized cell line derived from human ADENOCARCINOMA, ALVEOLAR basal epithelial cells isolated from the lungs of a male patient in 1972. The cell line is positive for KERATIN, can synthesize LECITHIN, and contains high levels of POLYUNSATURATED FATTY ACIDS in its PLASMA MEMBRANE. It is used as a model for PULMONARY ALVEOLI function and virus infections, as a TRANSFECTION host, and for PRECLINICAL DRUG EVALUATION. A549 Cell Line,A549 Cell,A549 Cell Lines,Cell Line, A549,Cell Lines, A549,Cell, A549,Cells, A549
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D012321 DNA-Directed RNA Polymerases Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992). DNA-Dependent RNA Polymerases,RNA Polymerases,Transcriptases,DNA-Directed RNA Polymerase,RNA Polymerase,Transcriptase,DNA Dependent RNA Polymerases,DNA Directed RNA Polymerase,DNA Directed RNA Polymerases,Polymerase, DNA-Directed RNA,Polymerase, RNA,Polymerases, DNA-Dependent RNA,Polymerases, DNA-Directed RNA,Polymerases, RNA,RNA Polymerase, DNA-Directed,RNA Polymerases, DNA-Dependent,RNA Polymerases, DNA-Directed
D012367 RNA, Viral Ribonucleic acid that makes up the genetic material of viruses. Viral RNA

Related Publications

Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
February 2020, Scientific reports,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
January 2013, Current medicinal chemistry,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
May 1987, Proceedings of the National Academy of Sciences of the United States of America,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
January 2018, Viral immunology,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
April 2003, The Journal of general virology,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
April 2011, Cell host & microbe,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
May 2006, Virology,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
August 2012, Microbes and infection,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
May 2020, Journal of virology,
Chi-Ping Chan, and Chun-Kit Yuen, and Pak-Hin Hinson Cheung, and Sin-Yee Fung, and Pak-Yin Lui, and Honglin Chen, and Kin-Hang Kok, and Dong-Yan Jin
May 2006, Virology,
Copied contents to your clipboard!