DOCSLIB.ORG

Interferon Action Revisited from Paula M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interferon Action Revisited from Paula M 374 Nature Vol. 269 29 September 1977 Interferon action revisited from Paula M. Pitha INTERFERONS are species-specific cellu­ feron in ~he medium, Vengris et al. VSV or vaccm1a virus, and measure­ lar glycoproteins synthesised by a wide (Virology 64, 410; 1975) demonstrated ment of virus ydeld. To achieve the variety of animal cells in response to that for the development of the anti­ effect close contact between the two viral infection (or various non-viral viral state interferon had to interact cell populations was required; the effect stimuli) which induce antiviral resist­ with the external cellular membrane of was not observed in cultures plated at ance in homologous cells. In interferon­ the cell producing interferon. low cell density. Actinomycin D treat­ treated cells, a wide variety of different The results obtained by several ment of the mouse cells blocked both viruses do not replicate well. It was groups (for example F. Ruddle at Yale the antiviral effect in the mouse cells shown with a majority of the viruses University, Connecticut, and F. C. and their ability to transfer resistance studied that the primary effect of inter­ Chany at INSERM, Paris) using to the heterologous cells. It seems, feron is a general inhibition of viral mouse- human cell hybrids demon­ therefore, that the transferred com­ .protein synthesis. In addition to this strated that the sensitivity to human pound may be a product of interferon block it has also been found that with interferon is governed by human induction rather than interferon itself. some viruses such as VSV and SV40 chromosome 21. Trisomy 21 cells were This conclusion, however, is based the transcription of viral mRNA is markedly more sensitive to human on experiments done in mass cultures decreased in interferon-treated cells. interferon than normal diploid cells or and the challenging viruses replicated Oncornavirus replication seems to be monosomy 21 cells (Tan et at. Science both in homologous and heterologous inhibited by interferon at the level of 186, 61; 1974; Chany et at. Proc. natn. cells. In the future much clearer data virus maturation and assembly. Acad. Sci. U.S.A . 12, 3129; 1975). would be obtained if t-he infecting virus 11he nature of the molecular mech­ Antibodies to hybrid cells containing could not replicate :in the cells homo­ anism ,by which interferon induces the human chromosome 21 were· found to logous to the interferon but only in antiviral state in the cell has not yet inhibit the antiviral effect of human the cells to which the antiviral com­ been clarified. Interferon by itself is interferon in human cells. Revel et al. pound was transferred. It has been not an antiviral agent. The antiviral (Nature 260, 139; 1976) suggested that shown previously that the effect of state does not develop in enucleated chromosome 21 codes for the receptor interferon is an all-or-none pheno­ cells or in cells treated with actino­ for human interferon on the cell menon in L cells and in chick embryo mycin D or cycloheximide. This in­ surface. cells (Chang et a!. J. gen. Viral. 20, dicates that the antiviral effect of inter­ T•he species specificity of interferons 139; 1973; Radke et at. J. Viral. 13, feron requires both transcription and seems to be also determined at the 623; 1974), and thus it should be translation of the cellular genome and receptor level. Recent data indicate possible to measure the transfer of leads to the proposal that t1here is an that in primate-mouse hybrid cells viral resistance from the cell in the interferon-induced antiviral protein containing only one or a few human antiviral state to t·he adjacent neigh­ (Taylor Biochern. biophys. R es. chromosomes interferon specificity is bour. Fluorescent antibody or infec­ Commun. 14, 447; 1964). The situation, due to the interaction with the receptor tious centre techniques could be used however, is not that simple; recent but the antiviral mechanism induced to confirm the requi.rement for cell--cell results from the laboratories of I. Kerr with both mouse and human interferon contact. (MRC, Mill Hill, London), P. Lengyel is of mouse orig.in (Chany, Biomedicine (Yale University, Connecticut) and M. Express 24, 148; 1976). This indicates One of the remarkable properties of Revel (Weizmann Institute of Science, that at least some components of the the interferon system is its high bio­ Rehovot) with cell-f.ree protein syn­ antiviral effect do not have a require­ logical activity. The specific activity of thesising systems, indicate that inter­ ment for species s_pecificity. Samuel both human and mouse interferon is feron treatment induces the synthesis and Joklik (Virology 15, 166; 1976) estimated to be dose to 10" units per mg protein (one unit is the amount of of several translational inhibitors. came to a similar conclusion when they interferon which inhibits vir.us replica­ The first step in the induction of the showed that interferon treatment tion by 50%). It is proba.ble that such a antiviral effect is the interaction of induced a ribosome-associated inhibitor system involves mechanisms which interferon with the cellular membrane of viral mRN A translation in cell-free amplify the initial response. Both the of a sensitive cell, and it has been systems that could be dissociated · from above described transfer of antiviral observed that the interferon binding ribosomes and inhibit the translation of resistance and the mobility of the inter­ involves both cellular ,gangliosides and viral mRNA in a heterologous cell­ feron receptors on the cell surface glycoproteins (Besancon & Ankel free protein synthesising system. (Lebon eta!. Proc Soc. exp. Bioi. Med. Nature 252, 478; 1974; Vengris et at. Tn this issue of Nature (page 422) 149, 108; 1975) may be amplification Virology 12, 486; 1976; Kohn et a!. Blalock and Baron from the University factors in the interferon system. Proc. natn. A cad. Sci. U.S.A . 73, 3695; of Texas at Galveston present another 1976). The cellular uptake of interferon t)-lpe of evidence that vhe interferon­ Currently it seems that the action of is not required for the antiviral effect induced antiviral 'machinery' may not interferon at the cellular surface (Ankel et al. Proc. natn. A cad. Sci. be species specific. The authors also resembles in many respects the action U.S.A . 70, 2360; 1973); the sensitivity suggest that the antiviral compound of the polypeptide hormones. The to interferon seems to be determined induced by interferon treatment of the major task for the future is to answer by a receptor located at the .plasma homologous cells can be transferred to the question of how the impulse from membrane. Using antiserum to inter­ the cell of the heterologous species and the cell membrane is transferred to feron, which neutralised all free inter- elicit in it resistance to viral infection. the nucleus. One possibility which T·he experiments are based on coculti­ remains to be determined is that vation of mouse cells (sensitive to the antiviral effect of interferon is Paula M . Pitha is Associate Professor of mouse interferon) with interferon­ mediated through a second message Oncology in the Cancer Center of the insensitive human cells in the presence such as cyclic AMP (Weber & Stewart Johns Hopkins University School of J. gen. 28, 363; 1975). Medicine. of mouse interferon, infection with Virol 0 © 1977 Nature Publishing Group.
Load more

Recommended publications
  • The Zinc-Finger Antiviral Protein Recruits the RNA Processing Exosome to Degrade the Target Mrna
    The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA Xuemin Guo, Jing Ma, Jing Sun, and Guangxia Gao* Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved November 3, 2006 (received for review August 14, 2006) Zinc-finger antiviral protein (ZAP) is a host antiviral factor that putative RNA helicase (Kiaa0052), and a protein that is specifically specifically inhibits the replication of Moloney murine leukemia phosphorylated in the M phase of the cell cycle (Mpp6) (36, 38). virus (MLV) and Sindbis virus (SIN) by preventing accumulation of The RNase-PH domain subunits and the S1/KH RNA-binding the viral mRNA in the cytoplasm. In previous studies, we demon- domain subunits are considered to be the core components of the strated that ZAP directly binds to its specific target mRNAs. In this exosome, whereas Kiaa0052 and Mpp6 are considered to be article, we provide evidence indicating that ZAP recruits the RNA accessory factors (36, 38). Yeast PM/Scl-100 is found only in the processing exosome to degrade the target RNA. ZAP comigrated nuclear exosome (36, 46). with the exosome in sucrose or glycerol velocity gradient centrif- The structure of the exosome is not yet determined. Based on the ugation. Immunoprecipitation of ZAP coprecipitated the exosome results of mammalian-two-hybrid and yeast-two-hybrid experi- components. In vitro pull-down assays indicated that ZAP directly ments (38, 56–59), the six RNase-PH domain-containing subunits interacted with the exosome component hRrp46p and that the are thought to assemble into a doughnut-shaped ring.
    [Show full text]
  • High Transdominant Revm10 Protein Levels Are Required to Inhibit HIV-1 Replication in Cell Lines and Primary T Cells: Implication for Gene Therapy of AIDS
    Gene Therapy (1997) 4, 128–139 1997 Stockton Press All rights reserved 0969-7128/97 $12.00 High transdominant RevM10 protein levels are required to inhibit HIV-1 replication in cell lines and primary T cells: implication for gene therapy of AIDS I Plavec1, M Agarwal1,KEHo2, M Pineda1, J Auten1, J Baker1, H Matsuzaki3, S Escaich4, M Bonyhadi1 and E Bo¨ hnlein1 1Progenesys Program, SyStemix Inc, 3155 Porter Drive, Palo Alto, CA 94304, USA Expression of antiviral genes in CD4+ T cells has been pro- uniformly higher than from internal promoters (eg CMV, posed as a strategy for gene therapy of AIDS. Over the PGK). Analysis of selected vectors in acutely and chron- past years, we and others have developed retroviral vec- ically HIV-infected cell lines suggested that threshold levels tors encoding the RevM10 protein, a dominant-negative of RevM10 expression are required to achieve inhibition of mutant of the HIV-1 Rev trans-activator protein. We could HIV replication. LTR-driven RevM10 expression also demonstrate gene transfer and inhibition of HIV-1 repli- yielded high steady-state protein levels in activated primary cation in cultured T cell lines and primary T cells. However, T cells resulting in inhibition of HIV replication, and there little is known about the levels of the antiviral protein was no apparent difference between the MoMLV, MPSV required to achieve a therapeutic effect, particularly in pri- and MESV-LTR vectors. However, RevM10 expression mary cells. In this report, we compare different vector was down-regulated in resting primary cells and conse- designs with regard to expression of the antiviral gene to quently anti-HIV efficacy was significantly reduced.
    [Show full text]
  • Extracellular Localization of Pokeweed Antiviral Protein MICHAEL P
    Proc. Natl. Acad. Sci. USA Vol. 83, pp. 5053-5056, July 1986 Biochemistry Extracellular localization of pokeweed antiviral protein MICHAEL P. READY*, DENNIS T. BROWNt, AND JON D. ROBERTUS** *Clayton Foundation Biochemical Institute, Department of Chemistry, and tCell Research Institute and Department of Microbiology, University of Texas, Austin, TX 78712 Communicated by Esmond E. Snell, March 24, 1986 ABSTRACT Pokeweed antiviral protein is an enzyme of molecule may well be inactive until it is processed and Mr 29,000 known to inactivate a wide variety of eukaryotic packaged in the seed. ribosomes. We have used electron microscopy to show that the However, the case is not so clear for proteins such as the antibody specific for the protein is bound within the cell wall pokeweed enzyme, which are not cytotoxic to animals. In matrix of leaf mesophyll cells from Phytolacca americana. Any addition, reports have suggested that pokeweed antiviral penetration or breakage of the cell wall and membrane could protein does not inhibit protein synthesis on pokeweed allow the enzyme to enter the cytoplasm, where it is likely to ribosomes (19, 20). If this were true, it would mean that inhibit protein synthesis in the damaged cell. We speculate that pokeweed could not shut down its own ribosomes if they pokeweed antiviral protein is a defensive agent whose principal were usurped by an invading virus. Recently we speculated 'function is probably antiviral. (5) that this state of affairs is unlikely; a protein that makes up as much as 0.5% of the plant's soluble protein and that Many higher plants contain proteins that enzymatically attacks ribosomes with a Kcat of 400 mol/mol per min must inhibit protein synthesis on eukaryotic ribosomes.
    [Show full text]
  • Interferon-Inducible Antiviral Effectors
    REVIEWS Interferon-inducible antiviral effectors Anthony J. Sadler and Bryan R. G. Williams Abstract | Since the discovery of interferons (IFNs), considerable progress has been made in describing the nature of the cytokines themselves, the signalling components that direct the cell response and their antiviral activities. Gene targeting studies have distinguished four main effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′,5′-oligoadenylate-synthetase-directed ribonuclease L pathway, the protein kinase R pathway and the ISG15 ubiquitin-like pathway. As discussed in this Review, these effector pathways individually block viral transcription, degrade viral RNA, inhibit translation and modify protein function to control all steps of viral replication. Ongoing research continues to expose additional activities for these effector proteins and has revealed unanticipated functions of the antiviral response. Pattern-recognition Interferon (IFN) was discovered more than 50 years ago in components of the IFNR signalling pathway (STAT1 receptors as an agent that inhibited the replication of influenza (signal transducer and activator of transcription 1), TYK2 (PRRs). Host receptors that can virus1. The IFN family of cytokines is now recognized as (tyrosine kinase 2) or UNC93B) die of viral disease, with sense pathogen-associated a key component of the innate immune response and the the defect in IFNAR (rather than IFNGR) signalling molecular patterns and initiate 6–9 signalling cascades that lead to first line of defence against viral infection. Accordingly, having the more significant role . an innate immune response. IFNs are currently used therapeutically, with the most The binding of type I IFNs to the IFNAR initiates a These can be membrane bound noteworthy example being the treatment of hepatitis C signalling cascade, which leads to the induction of more (such as Toll-like receptors) or virus (HCV) infection, and they are also used against than 300 IFN-stimulated genes (ISGs)10.
    [Show full text]
  • Since January 2020 Elsevier Has Created a COVID-19 Resource Centre with Free Information in English and Mandarin on the Novel Coronavirus COVID- 19
    Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Review To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes Melody M.H. Li, Margaret R. MacDonald, and Charles M. Rice Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA 0 0 Type I interferon (IFN) is one of the first lines of cellular and 2 -5 -oligoadenylate synthetase (OAS)/RNAseL func- defense against viral pathogens. As a result of IFN sig- tion to block translation to limit virus replication (Box 1). naling, a wide array of IFN-stimulated gene (ISG) pro- This review focuses on the more recently described ISGs ducts is upregulated to target different stages of the viral that regulate host or viral translation, localize to transla- life cycle. We review recent findings implicating a subset tionally silent granules, and interfere with miRNA-medi- of ISGs in translational regulation of viral and host ated silencing of host transcripts.
    [Show full text]
  • The Antiviral Protein Viperin Enhances the Host Interferon
    bioRxiv preprint doi: https://doi.org/10.1101/493098; this version posted December 11, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The Antiviral Protein Viperin Enhances The Host Interferon Response Following STING Activation Keaton Crosse1, Ebony Monson1, Monique Smith1, Yeu-Yang Tseng2, Kylie Van der Hoek3, Peter Revill4, David Tscharke2, Michael Beard3, Karla Helbig1 1 Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia 2 John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia 3 School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia 4 Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia Correspondence to be addressed to: Dr Karla Helbig Department of Physiology, Anatomy and Microbiology, La Trobe University 1 Kingsbury Drive, Bundoora, Vic, 3083 Email: [email protected] Key words: viperin, interferon stimulated genes, interferon, innate immunity, virus, STING, TBK1, dsDNA 1 bioRxiv preprint doi: https://doi.org/10.1101/493098; this version posted December 11, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Viperin is an interferon-inducible protein that is critical for eliciting an effective immune response against many diverse viral pathogens. As such, viperin has been implicated in interactions with many functionally unrelated host and viral proteins, making it increasingly difficult to determine a unifying mechanism of viperin’s antiviral activity.
    [Show full text]
  • Expression of Pokeweed Antiviral Protein in Transgenic Plants
    Plant Physiol. (1997) 114: 1113-1 121 Expression of Pokeweed Antiviral Protein in Transgenic Plants lnduces Virus Resistance in Grafted Wild-Type Plants lndependently of Salicylic Acid Accumulation and Pathogenesis-Related Protein Synthesis’ Sergey Smirnov, Vladimir Shulaev, and Nilgun E. Tumer* Center for Agricultura1 Molecular Biology and Department of Plant Pathology, Rutgers University, P.O. Box 231, New Brunswick, New Jersey 08903-0231 pokeweed (Phytolacca americana) plants. These proteins are Pokeweed antiviral protein (PAP), a 29-kD protein isolated from similar in molecular mass (29, 30, and 29.5 kD, respec- Phytolacca americana, inhibits translation by catalytically removing tively) but are expressed at different developmental stages a specific adenine residue from the large rRNA of the 60s subunit of and in different tissues of pokeweed (Wyatt and Shepherd, eukaryotic ribosomes. Transgenic tobacco (Nicofiana fabacum) 1969; Irvin et al., 1980; Barbieri et al., 1982). PAP depuri- plants expressing PAP or a variant (PAP-V) were shown to be resis- nates ribosomes from pokeweed and other plants (Bonness tant to a broad spectrum of plant viruses. Expression of PAP-v in et al., 19941, as well as mammalian, yeast, and bacterial transgenic plants induces synthesis of pathogenesis-related proteins ribosomes. In addition, PAI’ effectively inhibits infection and a very weak (~2-fold)increase in salicylic acid levels. Using by a number of different plant (Wyatt and Shepherd, 1969; reciproca1 grafting experiments, we demonstrate here that trans- Tomlinson et al., 1974; Chen et al., 1992) and animal viruses genic tobacco rootstocks expressing PAP-v induce resistance to (Tomlinson et al., 1974; Ussery et al., 1977), including hu- tobacco mosaic virus infection in both N.
    [Show full text]
  • CG Dinucleotide Suppression Enables Antiviral Defence Targeting Non-Self RNA Matthew A
    LETTER doi:10.1038/nature24039 CG dinucleotide suppression enables antiviral defence targeting non-self RNA Matthew A. Takata1, Daniel Gonçalves-Carneiro1, Trinity M. Zang1,2, Steven J. Soll1,2, Ashley York1, Daniel Blanco-Melo1 & Paul D. Bieniasz1,2 Vertebrate genomes exhibit marked CG suppression—that is, lower (Fig. 1f). Our synonymous mutagenesis coincidentally increased than expected numbers of 5′-CG-3′ dinucleotides1. This feature is the CG dinucleotide content in mutant segments to a level similar likely to be due to C-to-T mutations that have accumulated over to that of random sequence (Fig. 1f). We generated derivatives of hundreds of millions of years, driven by CG-specific DNA methyl mutant L, termed LCG and LOTH, respectively, containing only transferases and spontaneous methyl-cytosine deamination. Many mutations that generated new CG dinucleotides (37 of 145 original RNA viruses of vertebrates that are not substrates for DNA methyl mutations) or the 108 other mutations (Supplementary Data 1). transferases mimic the CG suppression of their hosts2–4. This We also generated mutants that maximized the CG or, as a further 4–6 property of viral genomes is unexplained . Here we show, using control, GC dinucleotide content in the same segment (LCG-HI and synonymous mutagenesis, that CG suppression is essential for LGC-HI) (Extended Data Table 1). These proviral plasmids each yielded HIV-1 replication. The deleterious effect of CG dinucleotides on similar levels of infectious virus following transfection of 293T cells HIV-1 replication was cumulative, associated with cytoplasmic RNA depletion, and was exerted by CG dinucleotides in both translated a GFP and non-translated exonic RNA sequences.
    [Show full text]
  • Prokaryotic Viperins Produce Diverse Antiviral Molecules
    Article Prokaryotic viperins produce diverse antiviral molecules https://doi.org/10.1038/s41586-020-2762-2 Aude Bernheim1, Adi Millman1, Gal Ofir1, Gilad Meitav1, Carmel Avraham1, Helena Shomar2, Masha M. Rosenberg2, Nir Tal2, Sarah Melamed1, Gil Amitai1 & Rotem Sorek1 ✉ Received: 25 February 2020 Accepted: 27 August 2020 Viperin is an interferon-induced cellular protein that is conserved in animals1. It Published online: xx xx xxxx has previously been shown to inhibit the replication of multiple viruses by producing Check for updates the ribonucleotide 3′-deoxy-3′,4′-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modifed ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems. Viperin is an antiviral protein that becomes highly expressed in cells genes involved in defence systems is a strong predictor that the genes in stimulated by interferons1. In humans, this protein has broad antiviral the cluster have a role in phage resistance8,9. We denoted the genes in the activity against DNA and RNA viruses, including human cytomegalovi- defensive cluster pVips (for prokaryotic viperin homologues). As pVips rus, West Nile virus, dengue virus, hepatitis C virus and HIV1,3.
    [Show full text]
  • Discovery of Another Anti-HIV Protein in the Search for the CD8+ Cell Anti-HIV Factor
    COMMENTARY COMMENTARY Discovery of another anti-HIV protein in the search for the CD8+ cell anti-HIV Factor Jay A. Levy1 purified cytokines, no human proteins linked Department of Medicine, University of California, San Francisco, CA 94143 to CD8+ cells have been found with the characteristics of CAF (11, 16). In PNAS, the research group led by Ian de + Nearly three decades ago, soon after the to the infected CD4 cells inhibited virus Belle reports the surprising finding that a recognition of AIDS and its causative agent, replication without affecting the viability of nuclear protein, TOE1 (target of EGR1, early + HIV, the first immune response against the the CD4 cells (1). growth response 1), could be CAF (17). TOE1 AIDS virus was identified: an unexpected This lack of cell killing was further sub- is found primarily in nucleoli and Cajal bod- + + anti-HIV activity of CD8 cells that did not stantiated when the CD8 cells were sepa- ies and is involved in a variety of intracellular + involve cell killing (1). This immune response rated by a filter from the HIV-infected CD4 events, including deadenylase activity and + differed from the classic CD8 cell antiviral cells. Virus replication was inhibited, and a spliceosome assembly (18, 19). TOE1 was ini- activity in which cytotoxic T lymphocytes kill soluble protease-sensitive factor, now known tially cloned by the de Belle laboratory and + + virus-infected cells (2). The CD8 cell non- as the CD8 cell antiviral factor (CAF), ap- found to bind to the p53 tumor suppressor – cytotoxic anti-HIV response (CNAR) became peared responsible (6 8).
    [Show full text]
  • The Short Form of the Zinc Finger Antiviral Protein Inhibits Influenza A
    VIRUS-CELL INTERACTIONS crossm The Short Form of the Zinc Finger Antiviral Protein Inhibits Influenza A Downloaded from Virus Protein Expression and Is Antagonized by the Virus-Encoded NS1 Qiannan Tang,a,b Xinlu Wang,a Guangxia Gao,a,b CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, http://jvi.asm.org/ Chinaa; University of Chinese Academy of Sciences, Beijing, Chinab ABSTRACT Zinc finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses. There are two ZAP isoforms arising from alternative Received 30 September 2016 Accepted 27 splicing, which differ only at the C termini. It was recently reported that the long October 2016 Accepted manuscript posted online 2 isoform (ZAPL) promotes proteasomal degradation of influenza A virus (IAV) proteins November 2016 PA and PB2 through the C-terminal poly(ADP-ribose) polymerase (PARP) domain, Citation Tang Q, Wang X, Gao G. 2017. The which is missing in the short form (ZAPS), and that this antiviral activity is antago- short form of the zinc finger antiviral protein on April 20, 2017 by NATIONAL SCIENCE LIBRARY, CAS nized by the viral protein PB1. Here, we report that ZAP inhibits IAV protein expres- inhibits influenza A virus protein expression and is antagonized by the virus-encoded NS1. sion in a PARP domain-independent manner. Overexpression of ZAPS inhibited the J Virol 91:e01909-16. https://doi.org/10.1128/ expression of PA, PB2, and neuraminidase (NA), and downregulation of the endoge- JVI.01909-16. nous ZAPS enhanced their expression.
    [Show full text]
  • Innate Immune Responses to Avian Influenza Viruses in Ducks
    veterinary sciences Review Innate Immune Responses to Avian Influenza Viruses in Ducks and Chickens Danyel Evseev 1,2 and Katharine E. Magor 1,2,* 1 Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada; [email protected] 2 Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E9, Canada * Correspondence: [email protected]; Tel.: +1-(780)-492-5498 Received: 2 November 2018; Accepted: 4 January 2019; Published: 10 January 2019 Abstract: Mallard ducks are important natural hosts of low pathogenic avian influenza (LPAI) viruses and many strains circulate in this reservoir and cause little harm. Some strains can be transmitted to other hosts, including chickens, and cause respiratory and systemic disease. Rarely, these highly pathogenic avian influenza (HPAI) viruses cause disease in mallards, while chickens are highly susceptible. The long co-evolution of mallard ducks with influenza viruses has undoubtedly fine-tuned many immunological host–pathogen interactions to confer resistance to disease, which are poorly understood. Here, we compare innate responses to different avian influenza viruses in ducks and chickens to reveal differences that point to potential mechanisms of disease resistance. Mallard ducks are permissive to LPAI replication in their intestinal tissues without overtly compromising their fitness. In contrast, the mallard response to HPAI infection reflects an immediate and robust induction of type I interferon and antiviral interferon stimulated genes, highlighting the importance of the RIG-I pathway. Ducks also appear to limit the duration of the response, particularly of pro-inflammatory cytokine expression. Chickens lack RIG-I, and some modulators of the signaling pathway and may be compromised in initiating an early interferon response, allowing more viral replication and consequent damage.
    [Show full text]