DOCSLIB.ORG

The Effect of Androstenediol on the Influenza Virus APR8/34 in A549 Cells THESIS Presented in Partial Fulfillment of the Require

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effect of Androstenediol on the Influenza Virus APR8/34 in A549 Cells THESIS Presented in Partial Fulfillment of the Require The Effect of Androstenediol on the Influenza Virus APR8/34 in A549 Cells THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Scott Franklin Wray, B.A. Graduate Program in Pathology The Ohio State University 2012 Master's Examination Committee: W. James Waldman, Advisor John F. Sheridan Copyright by Scott Franklin Wray 2012 Abstract A major problem in fighting influenza virus infections with the current trivalent vaccines and antivirals is the inherent genetic instability of the RNA-encoded proteins of the virus. Current vaccines induce neutralizing antibodies specific for two major surface antigens expressed on the virion. These two proteins are encoded by the hemagglutinin and neuraminidase genes respectively, and in these genes, there is a high rate of point mutation resulting in antigenic drift of the expressed proteins. A similar problem arises with antivirals where resistant strains develop or are selected for when antivirals are used in a widespread fashion. In other words, the virions that are sensitive to the antiviral are killed, whereas those that are resistant to the antiviral are free to infect susceptible individuals. Therefore, it would be beneficial to develop anti-influenza strategies that do not rely on treatments directed against the variable genes encoded by the virus. Based on previous work from our laboratory, we hypothesize that androstenediol inhibits influenza replication by modifying the host cell’s interaction with the virus. Our proposal is that treatment with androstenediol (AED), may lead to an approach that is not directed at the variable genes encoded by the viruses. Our results suggest that AED treatment may inhibit viral replication, as indicated by the influenza viral matrix protein, M1, gene expression. Additionally, our results exclude certain cellular mechanisms and suggest other possible mechanisms that will need to be examined in more detail. ii Dedication This document is dedicated to my family and friends. iii Acknowledgments I would like to acknowledge all my advisors, fellow laboratory members, and other faculty members for their guidance, encouragement, and support during the course of my training. iv Vita May 1999 .......................................................Liberty Union-Thurston High 2003................................................................B.A. Biology, Capital University 2003 to 2004 ..................................................Graduate Research Associate, Department of Integrated Biomedical Science, The Ohio State University 2004 to 2009 ..................................................Graduate Research Fellow, Department of Oral Biology, The Ohio State University 2009 to 2011 ..................................................Graduate Research Associate, Department of Integrated Biomedical Science, The Ohio State University 2011 to present ..............................................Master’s Student, Department of Pathology, The Ohio State University Publication(s) 1. Integrin engagement increases histone H3 acetylation and reduces histone H1 association with DNA in murine lung endothelial cells. Molecular Pharmacology. 68(2): 439-46, 2005. v Fields of Study Major Field: Pathology vi Table of Contents Abstract ............................................................................................................................... ii Dedication .......................................................................................................................... iii Acknowledgments.............................................................................................................. iv Vita ...................................................................................................................................... v List of Tables .................................................................................................................... iix List of Figures ..................................................................................................................... x List of Abbreviations ........................................................................................................ xii Chapter 1: Introduction ...................................................................................................... 1 Chapter 2: Androstenediol Suppresses Influenza Virus-Encoded M1 Gene Expression in Human Respiratory Epithelial Cells ................................................................................. 19 Introduction ................................................................................................................... 19 Methods ......................................................................................................................... 23 Results ........................................................................................................................... 28 Discussion ..................................................................................................................... 31 Chapter 3: Androstenediol’s Effect on Cellular Signaling and a Coalescing of Pattern Recognition Receptors ...................................................................................................... 42 vii Introduction ................................................................................................................... 42 Methods ......................................................................................................................... 44 Results ........................................................................................................................... 48 Discussion ..................................................................................................................... 51 Chapter 4: Determining Whether Androstenediol Modifies Influenza Virus-Encoded M1 Gene Expression Through the Androgen Receptor .......................................................... 57 Introduction ................................................................................................................... 57 Methods ......................................................................................................................... 59 Results ........................................................................................................................... 66 Discussion ..................................................................................................................... 69 Chapter 5: General Discussion......................................................................................... 80 References ......................................................................................................................... 91 viii List of Tables Table 2.1. Primer and TaqMan Probe Sequences of cytokines M1 and 18S for Real Time PCR ................................................................................................................................... 35 Table 3.1. PCR array analysis of AED activated genes in A549 cell culture with exposure to influenza virus Primer and TaqMan Probe Sequences of cytokines M1 and 18S for Real Time PCR .................................................................................................... 56 ix List of Figures Figure 2.1 Dose Curve of AED and its Effect on Influenza Virus M1 Gene Expression in A549 Lung Epithelial Cells .............................................................................................. 36 Figure 2.2 Time Course of AED and its Effect on Influenza Virus M1 Gene Expression in A549 Lung Epithelial Cells .......................................................................................... 37 Figure 2.3 Data of Influenza Virus M1 Gene Expression in A549 Lung Epithelial Cells ........................................................................................................................................... 38 Figure 2.4 Multiple Steroid Agonists and Antagonists Effect on Influenza Virus M1 Gene Expression in A549 Lung Epithelial Cells .............................................................. 39 Figure 2.5 The above images were used to determine whether AED had an effect on influenza viral entry .......................................................................................................... 40 Figure 2.6 The above images were used to determine whether AED had an effect on influenza viral entry .......................................................................................................... 41 Figure 3.1 Data of Interferon Beta Gene Expression in A549 Lung Epithelial Cells ..... 53 Figure 3.2 Focused microarray analysis of AED activated genes in A549 cell culture without exposure to influenza virus .................................................................................. 54 Figure 3.3 Data of Interferon Beta Gene Expression in A549 Lung Epithelial Cells With Exposure to Influenza Virus ............................................................................................. 55 Figure 4.1 Data of Influenza Virus M1 Gene Expression in A549 Lung Epithelial Cells Treated With a Dose Curve of Methyltrienolone (R1881) ............................................... 74 x Figure 4.2 Time Course of AED and its Effect on Influenza Virus M1 Gene Expression in A549 Lung Epithelial Cells .......................................................................................... 75 Figure
Load more

Recommended publications
  • Identification of Hsc70 As an Influenza Virus Matrix Protein (M1)
    FEBS Letters 580 (2006) 5785–5790 Identification of Hsc70 as an influenza virus matrix protein (M1) binding factor involved in the virus life cycle Ken Watanabea, Takayuki Fusea, Issay Asanoa, Fujiko Tsukaharab, Yoshiro Marub, Kyosuke Nagatac, Kaio Kitazatoa, Nobuyuki Kobayashia,* a Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan b Department of Pharmacology, Tokyo Women’s Medical University, School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan c Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan Received 22 August 2006; revised 13 September 2006; accepted 15 September 2006 Available online 27 September 2006 Edited by Felix Wieland nuclear export signal (NES), thus mechanism of M1-mediated Abstract Influenza virus matrix protein 1 (M1) has been shown to play a crucial role in the virus replication, assembly and bud- nuclear export of vRNP is still not well understood. ding. We identified heat shock cognate protein 70 (Hsc70) as a We herein identify heat shock cognate protein 70 (Hsc70), a M1 binding protein by immunoprecipitation and MALDI-TOF constitutive form of Hsp70 family protein, as an host factor(s) MS. The C terminal domain of M1 interacts with Hsc70. We which bind to M1 in infected cells by matrix-assisted laser found that Hsc70 does not correlate with the transport of M1 desorption ionization-time of flight mass spectrometry (MAL- to the nucleus, however, it does inhibit the nuclear export of DI-TOF MS). Heat shock proteins (Hsps) were induced by M1 and NP, thus resulting in the inhibition of viral production.
    [Show full text]
  • Distinct Contributions of Different Domains Within the HIV-1 Gag
    viruses Article Distinct Contributions of Different Domains within the HIV-1 Gag Polyprotein to Specific and Nonspecific Interactions with RNA Tomas Kroupa , Siddhartha A. K. Datta and Alan Rein * HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; [email protected] (T.K.); [email protected] (S.A.K.D.) * Correspondence: [email protected] Received: 24 February 2020; Accepted: 31 March 2020; Published: 2 April 2020 Abstract: Viral genomic RNA is packaged into virions with high specificity and selectivity. However, in vitro the Gag specificity towards viral RNA is obscured when measured in buffers containing physiological salt. Interestingly, when the binding is challenged by increased salt concentration, the addition of competing RNAs, or introducing mutations to Gag protein, the specificity towards viral RNA becomes detectable. The objective of this work was to examine the contributions of the individual HIV-1 Gag polyprotein domains to nonspecific and specific RNA binding and stability of the initial protein-RNA complexes. Using a panel of Gag proteins with mutations disabling different Gag-Gag or Gag-RNA interfaces, we investigated the distinct contributions of individual domains which distinguish the binding to viral and nonviral RNA by measuring the binding of the proteins to RNAs. We measured the binding affinity in near-physiological salt concentration, and then challenged the binding by increasing the ionic strength to suppress the electrostatic interactions and reveal the contribution of specific Gag–RNA and Gag–Gag interactions. Surprisingly, we observed that Gag dimerization and the highly basic region in the matrix domain contribute significantly to the specificity of viral RNA binding.
    [Show full text]
  • How Influenza Virus Uses Host Cell Pathways During Uncoating
    cells Review How Influenza Virus Uses Host Cell Pathways during Uncoating Etori Aguiar Moreira 1 , Yohei Yamauchi 2 and Patrick Matthias 1,3,* 1 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; [email protected] 2 Faculty of Life Sciences, School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; [email protected] 3 Faculty of Sciences, University of Basel, 4031 Basel, Switzerland * Correspondence: [email protected] Abstract: Influenza is a zoonotic respiratory disease of major public health interest due to its pan- demic potential, and a threat to animals and the human population. The influenza A virus genome consists of eight single-stranded RNA segments sequestered within a protein capsid and a lipid bilayer envelope. During host cell entry, cellular cues contribute to viral conformational changes that promote critical events such as fusion with late endosomes, capsid uncoating and viral genome release into the cytosol. In this focused review, we concisely describe the virus infection cycle and highlight the recent findings of host cell pathways and cytosolic proteins that assist influenza uncoating during host cell entry. Keywords: influenza; capsid uncoating; HDAC6; ubiquitin; EPS8; TNPO1; pandemic; M1; virus– host interaction Citation: Moreira, E.A.; Yamauchi, Y.; Matthias, P. How Influenza Virus Uses Host Cell Pathways during 1. Introduction Uncoating. Cells 2021, 10, 1722. Viruses are microscopic parasites that, unable to self-replicate, subvert a host cell https://doi.org/10.3390/ for their replication and propagation. Despite their apparent simplicity, they can cause cells10071722 severe diseases and even pose pandemic threats [1–3].
    [Show full text]
  • Dissecting Human Antibody Responses Against Influenza a Viruses and Antigenic Changes That Facilitate Immune Escape
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2018 Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape Seth J. Zost University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Allergy and Immunology Commons, Immunology and Infectious Disease Commons, Medical Immunology Commons, and the Virology Commons Recommended Citation Zost, Seth J., "Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape" (2018). Publicly Accessible Penn Dissertations. 3211. https://repository.upenn.edu/edissertations/3211 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3211 For more information, please contact [email protected]. Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape Abstract Influenza A viruses pose a serious threat to public health, and seasonal circulation of influenza viruses causes substantial morbidity and mortality. Influenza viruses continuously acquire substitutions in the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). These substitutions prevent the binding of pre-existing antibodies, allowing the virus to escape population immunity in a process known as antigenic drift. Due to antigenic drift, individuals can be repeatedly infected by antigenically distinct influenza strains over the course of their life. Antigenic drift undermines the effectiveness of our seasonal influenza accinesv and our vaccine strains must be updated on an annual basis due to antigenic changes. In order to understand antigenic drift it is essential to know the sites of antibody binding as well as the substitutions that facilitate viral escape from immunity.
    [Show full text]
  • Assessment of the Interaction Between the Human
    VARIATIONS IN THE V3 CROWN OF HIV-1 ENVELOPE IMPACT AFFINITY FOR CCR5 AND AFFECT ENTRY AND REPLICATIVE FITNESS By MICHAEL ANDREW LOBRITZ Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation advisor: Eric J. Arts, Ph.D. Department of Molecular Biology and Microbiology CASE WESTERN RESERVE UNIVERSITY August 2007 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the dissertation of ______________________________________________________ candidate for the Ph.D. degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Table of Contents Chapter 1: Introduction........................................................................................................................16 1.A. HIV and AIDS..............................................................................................17 1.B. Retroviruses: Structure, Organization, and Replication...............................20 1.B.1. HIV-1 Genome...............................................................................20 1.B.2. HIV-1 Particle................................................................................23
    [Show full text]
  • Replication of HIV-1 Envelope Protein Cytoplasmic Domain Variants in Permissive and Restrictive Cells T
    Virology 538 (2019) 1–10 Contents lists available at ScienceDirect Virology journal homepage: www.elsevier.com/locate/virology Replication of HIV-1 envelope protein cytoplasmic domain variants in permissive and restrictive cells T ∗ August O. Staubus, Ayna Alfadhli, Robin Lid Barklis, Eric Barklis Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA ARTICLE INFO ABSTRACT Keywords: Wild type (WT) HIV-1 envelope (Env) protein cytoplasmic tails (CTs) appear to be composed of membrane- HIV-1 proximal, N-terminal unstructured regions, and three C-terminal amphipathic helices. Previous studies have Replication shown that WT and CT-deleted (ΔCT) Env proteins are incorporated into virus particles via different mechan- Envelope protein isms. WT Env proteins traffic to cell plasma membranes (PMs), are rapidly internalized, recycle to PMs, and are Cytoplasmic tail incorporated into virions in permissive and restrictive cells in a Gag matrix (MA) protein-dependent fashion. In contrast, previously described ΔCT proteins do not appear to be internalized after their arrival to PMs, and do not require MA, but are only incorporated into virions in permissive cell lines. We have analyzed a new set of HIV-1 CT variants with respect to their replication in permissive and restrictive cells. Our results provide novel details as to how CT elements regulate HIV-1 Env protein function. 1. Introduction et al., 2018; Ohno et al., 1997; Wyss et al., 2001). Internalized Env proteins either are shunted off to lysosomes for degradation, or return The pathways by which HIV-1 envelope (Env) proteins become in- to PMs on recycling endosomes in a pathway that is dependent, in corporated into virions are complicated and incompletely elucidated certain cell types, on the Rab11 coupling protein FIP1C (Qi et al., 2013, (Checkley et al., 2011).
    [Show full text]
  • Through a Combination of Continual Antigenic Drift of Surface Proteins and High Transmission Rates the Identity of Circulating I
    Title: Computer-assisted vaccine design Hao Zhou, Ramdas S. Pophale, and Michael W. Deem Departments of Bioengineering and Physics & Astronomy Rice University Houston, TX, USA Abstract We define a new parameter to quantify the antigenic distance between two H3N2 influenza strains: we use this parameter to measure antigenic distance between circulating H3N2 strains and the closest vaccine component of the influenza vaccine. For the data between 1971 and 2004, the measure of antigenic distance correlates better with efficacy in humans of the H3N2 influenza A annual vaccine than do current state of the art measures of antigenic distance such as phylogenetic sequence analysis or ferret antisera inhibition assays. We suggest that this measure of antigenic distance could be used to guide the design of the annual flu vaccine. We combine the measure of antigenic distance with a multiple-strain avian influenza transmission model to study the threat of simultaneous introduction of multiple avian influenza strains. For H3N2 influenza, the model is validated against observed viral fixation rates and epidemic progression rates from the World Health Organization FluNet – Global Influenza Surveillance Network. We find that a multiple-component avian influenza vaccine is helpful to control a simultaneous multiple introduction of bird-flu strains. We introduce Population at Risk (PaR) to quantify the risk of a flu pandemic, and calculate by this metric the improvement that a multiple vaccine offers. Computer-assisted vaccine design Introduction Circulating influenza virus uses the ability to change its surface proteins, along with its high transmission rate, to flummox the adaptive immune response of the host. The random accumulation of mutations in the hemagglutinin (HA) and neuraminidase (NA) epitopes, the regions on surface of the viral proteins that are recognized by host antibodies, pose a formidable challenge to the design of an effective annual flu vaccine.
    [Show full text]
  • Antigenic Variation in Vector-Borne Pathogens
    Synopsis Antigenic Variation in Vector-Borne Pathogens Alan G. Barbour* and Blanca I. Restrepo† *University of California Irvine, Irvine, California; and †Corporación para Investigaciones Biológicas, Medellín, Colombia Several pathogens of humans and domestic animals depend on hematophagous arthropods to transmit them from one vertebrate reservoir host to another and maintain them in an environment. These pathogens use antigenic variation to prolong their circulation in the blood and thus increase the likelihood of transmission. By convergent evolution, bacterial and protozoal vector-borne pathogens have acquired similar genetic mechanisms for successful antigenic variation. Borrelia spp. and Anaplasma marginale (among bacteria) and African trypanosomes, Plasmodium falciparum, and Babesia bovis (among parasites) are examples of pathogens using these mechanisms. Antigenic variation poses a challenge in the development of vaccines against vector- borne pathogens. What Is Antigenic Variation? original antigen is archived in the cell and can be Immunodominant antigens are commonly used in the future. The adaptive immune system used to distinguish strains of a species of of an infected vertebrate selects against the pathogens. These antigens can vary from strain original infecting serotype, but that specific to strain to the extent that the strain-specific response is ineffective against new variants. One immune responses of vertebrate reservoirs example of antigenic variation occurs in determine the population structure of the B. hermsii, a cause of tickborne relapsing fever pathogen. One such strain-defining antigen is (4), which has a protein homologous to the OspC the OspC outer membrane protein of the Lyme protein of B. burgdorferi. However, instead of a disease spirochete Borrelia burgdorferi in the single version of this gene, each cell of B.
    [Show full text]
  • Evolution and Adaptation of the Avian H7N9 Virus Into the Human Host
    microorganisms Review Evolution and Adaptation of the Avian H7N9 Virus into the Human Host Andrew T. Bisset 1,* and Gerard F. Hoyne 1,2,3,4 1 School of Health Sciences, University of Notre Dame Australia, Fremantle WA 6160, Australia; [email protected] 2 Institute for Health Research, University of Notre Dame Australia, Fremantle WA 6160, Australia 3 Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Nedlands WA 6009, Australia 4 School of Medical and Health Sciences, Edith Cowan University, Joondalup WA 6027, Australia * Correspondence: [email protected] Received: 19 April 2020; Accepted: 19 May 2020; Published: 21 May 2020 Abstract: Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice.
    [Show full text]
  • Recitation 21 – Fall 2018 (Note: the Recitation Summary Should NOT Be Regarded As the Substitute for Lectures) (This Material Is COPYRIGHT Protected.)
    7.016: Fall 2018: MIT 7.016 Recitation 21 – Fall 2018 (Note: The recitation summary should NOT be regarded as the substitute for lectures) (This material is COPYRIGHT protected.) Summary of Lectures 32 (12/3) & 33 (12/5): Viruses: Viruses are obligate intracellular parasites. They consist of a protein coat (capsid) surrounding a genome, which encodes for proteins. These may include structural or coat proteins, other proteins necessary to get inside the host cell and make copies of the viral genome and the proteins that provide the virus with the anti–host defense system. Non-enveloped/ naked viruses do not have a lipid bilayer surrounding their capsid. They typically dock onto a protein on the surface of the target cells and inject their genomes into the host. Enveloped viruses have a lipid bilayer. They fuse their own membrane with the host membrane, such that the entire viral particle is endocytosed into the host cell. Once a virus is inside its host, it takes over the host machinery and uses it to make coat proteins and viral genomes. The genomes are then packaged into the coats and the new viral particles escape from the host cell either by lysing the cell or budding off from the cell. Viral genomes can be composed of either DNA or RNA. They can be single-stranded or double- stranded. There are two types of single stranded RNA viruses: plus (+) stranded or minus (-) stranded. The plus (+) stranded RNA genome can be directly read and translated by the host cell translation machinery. So these viruses bring only their genome, with no additional proteins, into the host cells at the time of infection.
    [Show full text]
  • Phosphorylation of the M2 Protein of Influenza a Virus Is Not Essential for Virus Viability
    VIROLOGY 252, 54±64 (1998) ARTICLE NO. VY989384 Phosphorylation of the M2 Protein of Influenza A Virus Is Not Essential for Virus Viability Joanne M. Thomas, Mark P. Stevens, Neil Percy,1 and Wendy S. Barclay2 School of Animal and Microbial Sciences, University of Reading, Whiteknights, UK RG6 6AJ Received May 14, 1998; returned to author for revision June 12, 1998; accepted August 18, 1998 M2 is a minor component of the influenza A virus envelope. The cytoplasmic tail of the M2 protein is posttranslationally modified in the infected cell by palmitylation and phosphorylation. The primary site for phosphorylation of the M2 cytoplasmic tail is serine 64, which is highly conserved yet not required for the activity of the M2 ion channel. Using an exogenous incorporation assay, we have shown that incorporation of M2 into virus particles is type-specific and does not require phosphorylation of the cytoplasmic tail. In addition, phosphorylation of the cytoplasmic tail is not required for the directional transport of M2 in polarized MDCK cells. Using a reverse genetics and reassortment procedure, we generated a virus (Ra) specifically mutated in segment 7 such that the M2 cytoplasmic tail could no longer be phosphorylated. The virus was found to grow as well as wild-type virus in tissue culture and in eggs, was stable on passage in these systems, and possessed no second-site mutations in the engineered RNA segment. In vivo Ra replicated in Balb/c mice at least as well as the parent strain A/WSN/33. These studies indicate that phosphorylation of the M2 cytoplasmic tail is not required for in vitro or in vivo replication of influenza A virus.
    [Show full text]
  • Respiratory Syncytial Virus and Coronaviruses
    Chapter 3 Structural and Functional Aspects of Viroporins in Human Respiratory Viruses: Respiratory Syncytial Virus and Coronaviruses Wahyu Surya, Montserrat Samsó and Jaume Torres Additional information is available at the end of the chapter http://dx.doi.org/10.5772/53957 1. Introduction Viroporins are an increasingly recognized class of small viral membrane proteins (~60-120 amino acids) which oligomerize to produce hydrophilic pores at the membranes of virus- infected cells [1]. The existence of ‘viroporins’ was proposed more than 30 years ago after observing enhanced membrane permeability in infected cells [2]. These proteins form oligomers of defined size, and can act as proton or ion channels, and in general enhancing membrane permeability in the host [3]. Even though viroporins are not essential for the rep‐ lication of viruses, their absence results in attenuated or weakened viruses or changes in tropism (organ localization) and therefore diminished pathological effects [4, 5]. In addition to having one – sometimes two – α-helical transmembrane (TM) domain(s), viro‐ porins usually contain additional extramembrane regions that are able to make contacts with viral or host proteins. Indeed, the network of interactions of viroporins with other viral or cellular proteins is key to understand the regulation of viral protein trafficking through the vesicle system, viral morphogenesis and pathogenicity. In general, viroporins participate in the entry or release of viral particles into or out of cells, and membrane permeabilization may be a desirable functionality for the virus. Indeed, sev‐ eral viral proteins that are not viroporins are known to affect membrane permeabilization, e.g., A38L protein of vaccinia virus, a 33-kDa glycoprotein that allows Ca2+ influx and indu‐ ces necrosis in infected cells [6].
    [Show full text]