DOCSLIB.ORG

Protein Composition of the Hepatitis a Virus Quasi-Envelope

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Protein Composition of the Hepatitis a Virus Quasi-Envelope Protein composition of the hepatitis A virus quasi-envelope Kevin L. McKnighta,b,c, Ling Xiec,d, Olga González-Lópeza,b,c, Efraín E. Rivera-Serranoa,b,c, Xian Chenc,d, and Stanley M. Lemona,b,c,1 aDepartment of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292; bDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292; cLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295; and dDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7260 Edited by Mary K. Estes, Baylor College of Medicine, Houston, TX, and approved April 12, 2017 (received for review November 27, 2016) The Picornaviridae are a diverse family of RNA viruses including many within extracellular vesicles before cell lysis, often with many pathogens of medical and veterinary importance. Classically consid- capsids packaged within a single vesicle (4–6). The cellular egress ered “nonenveloped,” recent studies show that some picornaviruses, of these classically nonenveloped viruses in membrane-bound notably hepatitis A virus (HAV; genus Hepatovirus) and some mem- vesicles has blurred the distinction between enveloped and bers of the Enterovirus genus, are released from cells nonlytically in nonenveloped viruses and has important implications for path- membranous vesicles. To better understand the biogenesis of quasi- ogenesis (2). enveloped HAV (eHAV) virions, we conducted a quantitative proteo- Several lines of evidence indicate that the biogenesis of quasi- mics analysis of eHAV purified from cell-culture supernatant fluids by enveloped eHAV virions is dependent upon components of the isopycnic ultracentrifugation. Amino acid-coded mass tagging (AACT) endosomal sorting complex required for transport (ESCRT). For with stable isotopes followed by tandem mass spectrometry sequenc- example, the ESCRT-associated protein ALIX (PDCD6IP) in- ing and AACT quantitation of peptides provided unambiguous iden- teracts with assembled HAV capsids, and RNAi-mediated tification of proteins associated with eHAV versus unrelated knockdown of ALIX expression inhibits the release of quasi- extracellular vesicles with similar buoyant density. Multiple peptides enveloped virus from infected cells (2). Although the size and were identified from HAV capsid proteins (53.7% coverage), but none density of eHAV vesicles are consistent with an exosome-like from nonstructural proteins, indicating capsids are packaged as cargo origin in multivesicular bodies (MVBs) (2, 3), eHAV bio- into eHAV vesicles via a highly specific sorting process. Other eHAV- genesis remains incompletely defined and the protein composi- associated proteins (n = 105) were significantly enriched for compo- tion of the membranes surrounding the quasi-enveloped capsid is nents of the endolysosomal system (>60%, P < 0.001) and included unknown. In contrast, the extracellular vesicles involved in egress many common exosome-associated proteins such as the tetraspanin CD9 and dipeptidyl peptidase 4 (DPP4) along with multiple endoso- of enteroviruses have been suggested to be derived from auto- mal sorting complex required for transport III (ESCRT-III)-associated phagosomes, as they contain lipidated LC3-II, a marker of proteins. Immunoprecipitation confirmed that DPP4 is displayed on autophagy, and disrupting autophagy blocks their release (4, 6). the surface of eHAV produced in cell culture or present in sera from However, the protein composition of these extracellular vesicles humans with acute hepatitis A. No LC3-related peptides were identi- also has yet to be comprehensively investigated. Thus, for both fied by mass spectrometry. RNAi depletion studies confirmed that hepatoviruses and enteroviruses, the cellular mechanisms un- ESCRT-III proteins, particularly CHMP2A, function in eHAV biogenesis. derlying the biogenesis of membrane-wrapped extracellular vi- In addition to identifying surface markers of eHAV vesicles, the results rions remain largely obscure and the protein composition of their support an exosome-like mechanism of eHAV egress involving endo- membranes unknown. somal budding of HAV capsids into multivesicular bodies. Significance exosome | multivesicular body | ESCRT | extracellular vesicle | picornavirus MICROBIOLOGY The nonlytic cellular egress of picornaviruses in extracellular vesi- he Picornaviridae are a large and diverse family of positive- cles is likely to be important in disease pathogenesis, but the Tstrand RNA viruses that include numerous pathogens (1). mechanism(s) underlying this process and the origins of the Classically considered “nonenveloped,” these viruses package membranes surrounding virions exiting the cell are poorly un- their single-stranded genomes within stable icosahedral protein derstood. We describe a quantitative proteomics analysis of quasi- capsids that are released from cells following cell lysis. However, enveloped hepatitis A virus (eHAV) virions that shows capsids are recent work has revealed that several picornaviruses gain egress selected as cargo for vesicular exportviaahighlyspecificprocess, from cells in a nonlytic fashion within the lumen of extracellular and that infectious eHAV virions possess a host protein comple- vesicles shed from the cell. Most notably, hepatitis A virus ment similar to that of exosomes with CD9 and DPP4 displayed on (HAV; genus Hepatovirus), an important cause of enterically their surface. eHAV-associated proteins are highly enriched for transmitted hepatitis in humans, replicates without cytopathic endolysosomal components and lack markers of autophagy, sug- effect and is released from cells as membrane-wrapped, “quasi- gesting an exosome-like mechanism of endosomal sorting complex enveloped” (eHAV) virions similar in size and density to exo- required for transport-mediated eHAV biogenesis involving endo- somes (2). eHAV virions have been identified in sera collected somal budding that is distinct from the autophagosome-mediated from persons with acute hepatitis A, as well as in supernatant release proposed previously for enteroviruses. fluids of infected cell cultures. These virions are completely Author contributions: K.L.M., O.G.-L., E.E.R.-S., X.C., and S.M.L. designed research; K.L.M., cloaked in host-derived membranes that protect the capsid from L.X., O.G.-L., and E.E.R.-S. performed research; K.L.M., L.X., O.G.-L., E.E.R.-S., X.C., and neutralizing antibody until the quasi-envelope is degraded within S.M.L. analyzed data; and K.L.M., E.E.R.-S., and S.M.L. wrote the paper. an endosomal compartment (2, 3). Nevertheless, they have The authors declare no conflict of interest. specific infectivity similar to naked, nonenveloped HAV particles This article is a PNAS Direct Submission. in cell culture. Coxsackievirus B, poliovirus, and many other 1To whom correspondence should be addressed. Email: [email protected]. members of the genus Enterovirus typically cause lytic infections This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. in cultured cells. However, viruses in this genus are also released 1073/pnas.1619519114/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1619519114 PNAS | June 20, 2017 | vol. 114 | no. 25 | 6587–6592 Downloaded by guest on September 30, 2021 Here we describe the results of a quantitative proteomics study in the opposing medium. The samples were then subjected to that defines the protein composition of the quasi-enveloped proteolytic digestion, and peptide fragments were identified by eHAV virion and points to an endosomal, MVB-like origin for liquid chromatography-tandem mass spectrometry (LC-MS/MS) these unusual infectious particles. and quantified by AACT (SI Materials and Methods). Two in- dependent, reverse AACT labeling experiments were carried out, Results each with H and L labeling of virus (thus we studied a total of four We adopted a quantitative proteomics approach incorporating independent virus samples). In the second experiment, virus and metabolic amino acid-coded mass tagging with stable isotopes mock-infected supernatant fluid concentrates were mixed be- (AACT; also known as SILAC) (7, 8) to unambiguously distin- fore, rather than following, isopycnic ultracentrifugation. guish eHAV-associated proteins from proteins present in exo- A total of 638 proteins were identified by the presence of at least somes similar in size and density to eHAV virions. Supernatant one unique peptide in at least one of the four samples when fluids from infected Huh-7.5 human hepatoma cell cultures main- screened against the human UniProt database and HAV polyprotein 13 13 12 12 tained in [ C6]Lys/[ C6]Arg (“heavy”;H)or[ C6]Lys/[ C6]Arg sequence. Of these, 294 were present in both H and L virus samples. (“light”; L) media were subjected to low-speed centrifugation at Multiple peptides were derived from the four structural proteins 10,000 × g to remove large extracellular vesicles (9). eHAV virions of HAV (Fig. S1). One peptide spanned the VP4–VP2 cleavage remaining in the medium were concentrated by ultracentrifugation (QGIFQTVGSGLDHILSLA^DIEEEQMIQSVDR), suggesting at 100,000 × g and then purified by isopycnic equilibrium ultra- that some empty capsids may have been present in the eHAV centrifugation in preformed iodixanol gradients (see SI Materials preparations. Another peptide spanned the VP1pX cleavage and Methods for details). Fractions containing virus were identified
Load more

Recommended publications
  • Guide for Common Viral Diseases of Animals in Louisiana
    Sampling and Testing Guide for Common Viral Diseases of Animals in Louisiana Please click on the species of interest: Cattle Deer and Small Ruminants The Louisiana Animal Swine Disease Diagnostic Horses Laboratory Dogs A service unit of the LSU School of Veterinary Medicine Adapted from Murphy, F.A., et al, Veterinary Virology, 3rd ed. Cats Academic Press, 1999. Compiled by Rob Poston Multi-species: Rabiesvirus DCN LADDL Guide for Common Viral Diseases v. B2 1 Cattle Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 2 Deer and Small Ruminants Please click on the principle system involvement Generalized viral disease Respiratory viral disease Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 3 Swine Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 4 Horses Please click on the principle system involvement Generalized viral diseases Neurological viral diseases Respiratory viral diseases Enteric viral diseases Abortifacient/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 5 Dogs Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Back to the Beginning DCN LADDL Guide for Common Viral Diseases v.
    [Show full text]
  • Rapid Identification of Known and New RNA Viruses from Animal Tissues
    Rapid Identification of Known and New RNA Viruses from Animal Tissues Joseph G. Victoria1,2*, Amit Kapoor1,2, Kent Dupuis3, David P. Schnurr3, Eric L. Delwart1,2 1 Department of Molecular Virology, Blood Systems Research Institute, San Francisco, California, United States of America, 2 Department of Laboratory Medicine, University of California, San Francisco, California, United States of America, 3 Viral and Rickettsial Disease Laboratory, Division of Communicable Disease Control, California State Department of Public Health, Richmond, California, United States of America Abstract Viral surveillance programs or diagnostic labs occasionally obtain infectious samples that fail to be typed by available cell culture, serological, or nucleic acid tests. Five such samples, originating from insect pools, skunk brain, human feces and sewer effluent, collected between 1955 and 1980, resulted in pathology when inoculated into suckling mice. In this study, sequence-independent amplification of partially purified viral nucleic acids and small scale shotgun sequencing was used on mouse brain and muscle tissues. A single viral agent was identified in each sample. For each virus, between 16% to 57% of the viral genome was acquired by sequencing only 42–108 plasmid inserts. Viruses derived from human feces or sewer effluent belonged to the Picornaviridae family and showed between 80% to 91% amino acid identities to known picornaviruses. The complete polyprotein sequence of one virus showed strong similarity to a simian picornavirus sequence in the provisional Sapelovirus genus. Insects and skunk derived viral sequences exhibited amino acid identities ranging from 25% to 98% to the segmented genomes of viruses within the Reoviridae family. Two isolates were highly divergent: one is potentially a new species within the orthoreovirus genus, and the other is a new species within the orbivirus genus.
    [Show full text]
  • Single-Cell RNA Sequencing Demonstrates the Molecular and Cellular Reprogramming of Metastatic Lung Adenocarcinoma
    ARTICLE https://doi.org/10.1038/s41467-020-16164-1 OPEN Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma Nayoung Kim 1,2,3,13, Hong Kwan Kim4,13, Kyungjong Lee 5,13, Yourae Hong 1,6, Jong Ho Cho4, Jung Won Choi7, Jung-Il Lee7, Yeon-Lim Suh8,BoMiKu9, Hye Hyeon Eum 1,2,3, Soyean Choi 1, Yoon-La Choi6,10,11, Je-Gun Joung1, Woong-Yang Park 1,2,6, Hyun Ae Jung12, Jong-Mu Sun12, Se-Hoon Lee12, ✉ ✉ Jin Seok Ahn12, Keunchil Park12, Myung-Ju Ahn 12 & Hae-Ock Lee 1,2,3,6 1234567890():,; Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell tran- scriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions. 1 Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
    [Show full text]
  • Orbiviruses: a North American Perspective
    VECTOR-BORNE AND ZOONOTIC DISEASES Volume 15, Number 6, 2015 ORIGINAL ARTICLES ª Mary Ann Liebert, Inc. DOI: 10.1089/vbz.2014.1699 Orbiviruses: A North American Perspective D. Scott McVey,1 Barbara S. Drolet,1 Mark G. Ruder,1 William C. Wilson,1 Dana Nayduch,1 Robert Pfannenstiel,1 Lee W. Cohnstaedt,1 N. James MacLachlan,2 and Cyril G. Gay3 Abstract Orbiviruses are members of the Reoviridae family and include bluetongue virus (BTV) and epizootic hem- orrhagic disease virus (EHDV). These viruses are the cause of significant regional disease outbreaks among livestock and wildlife in the United States, some of which have been characterized by significant morbidity and mortality. Competent vectors are clearly present in most regions of the globe; therefore, all segments of production livestock are at risk for serious disease outbreaks. Animals with subclinical infections also serve as reservoirs of infection and often result in significant trade restrictions. The economic and explicit impacts of BTV and EHDV infections are difficult to measure, but infections are a cause of economic loss for producers and loss of natural resources (wildlife). In response to United States Animal Health Association (USAHA) Resolution 16, the US Department of Agriculture (USDA), in collaboration with the Department of the Interior (DOI), organized a gap analysis workshop composed of international experts on Orbiviruses. The workshop participants met at the Arthropod-Borne Animal Diseases Research Unit in Manhattan, KS, May 14–16, 2013, to assess the available scientific information and status of currently available countermeasures to effectively control and mitigate the impact of an outbreak of an emerging Orbivirus with epizootic potential, with special emphasis given to BTV and EHDV.
    [Show full text]
  • Cell Communication and Signaling Biomed Central
    Cell Communication and Signaling BioMed Central Review Open Access Extravasation of leukocytes in comparison to tumor cells Carina Strell and Frank Entschladen* Address: Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany Email: Carina Strell - [email protected]; Frank Entschladen* - [email protected] * Corresponding author Published: 4 December 2008 Received: 18 November 2008 Accepted: 4 December 2008 Cell Communication and Signaling 2008, 6:10 doi:10.1186/1478-811X-6-10 This article is available from: http://www.biosignaling.com/content/6/1/10 © 2008 Strell and Entschladen; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The multi-step process of the emigration of cells from the blood stream through the vascular endothelium into the tissue has been termed extravasation. The extravasation of leukocytes is fairly well characterized down to the molecular level, and has been reviewed in several aspects. Comparatively little is known about the extravasation of tumor cells, which is part of the hematogenic metastasis formation. Although the steps of the process are basically the same in leukocytes and tumor cells, i.e. rolling, adhesion, transmigration (diapedesis), the molecules that are involved are different. A further important difference is that leukocyte interaction with the endothelium changes the endothelial integrity only temporarily, whereas tumor cell interaction leads to an irreversible damage of the endothelial architecture. Moreover, tumor cells utilize leukocytes for their extravasation as linkers to the endothelium.
    [Show full text]
  • Peruvian Horse Sickness Virus and Yunnan Orbivirus, Isolated from Vertebrates and Mosquitoes in Peru and Australia
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Virology 394 (2009) 298–310 Contents lists available at ScienceDirect Virology journal homepage: www.elsevier.com/locate/yviro Peruvian horse sickness virus and Yunnan orbivirus, isolated from vertebrates and mosquitoes in Peru and Australia Houssam Attoui a,⁎,1, Maria Rosario Mendez-lopez b,⁎,1, Shujing Rao c,1, Ana Hurtado-Alendes b,1, Frank Lizaraso-Caparo b, Fauziah Mohd Jaafar a, Alan R. Samuel a, Mourad Belhouchet a, Lindsay I. Pritchard d, Lorna Melville e, Richard P. Weir e, Alex D. Hyatt d, Steven S. Davis e, Ross Lunt d, Charles H. Calisher f, Robert B. Tesh g, Ricardo Fujita b, Peter P.C. Mertens a a Department of Vector Borne Diseases, Institute for Animal Health, Pirbright, Woking, Surrey, GU24 0NF, UK b Research Institute and Institute of Genetics and Molecular Biology, Universidad San Martín de Porres Medical School, Lima, Perú c Clemson University, 114 Long Hall, Clemson, SC 29634-0315, USA d Australian Animal Health Laboratory, CSIRO, Geelong, Victoria, Australia e Northern Territory Department of Primary Industries, Fisheries and Mines, Berrimah Veterinary Laboratories, Berrimah, Northern Territory 0801, Australia f Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA g Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, USA article info abstract Article history: During 1997, two new viruses were isolated from outbreaks of disease that occurred in horses, donkeys, Received 11 June 2009 cattle and sheep in Peru.
    [Show full text]
  • Lysosomal Membrane Glycoproteins Bind Cholesterol and Contribute to Lysosomal Cholesterol Export
    1 Lysosomal membrane glycoproteins bind cholesterol and 2 contribute to lysosomal cholesterol export 3 4 Jian Li and Suzanne R. Pfeffer* 5 Department of Biochemistry, Stanford University School of Medicine 6 Stanford, CA USA 94305-5307 7 8 *Correspondence to: [email protected]. 9 10 Abstract: LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins 11 that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. 12 LAMP2 deficiency causes Danon’s disease, an X-linked hypertrophic cardiomyopathy. LAMP2 13 is needed for chaperone-mediated autophagy, and its expression improves tissue function in 14 models of aging. We show here that LAMP1 and LAMP2 bind cholesterol in a manner that 15 buries the cholesterol 3β-hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that 16 export cholesterol from lysosomes. Quantitation of cellular LAMP2 and NPC1 protein levels 17 suggest that LAMP proteins represent a significant cholesterol binding site at the lysosome 18 limiting membrane, and may signal cholesterol availability. Functional rescue experiments show 19 that the ability of LAMP2 to facilitate cholesterol export from lysosomes relies on its ability to 20 bind cholesterol directly. 21 22 23 Introduction 24 Eukaryotic lysosomes are acidic, membrane-bound organelles that contain proteases, lipases and 25 nucleases and degrade cellular components to regenerate catabolic precursors for cellular use (1- 26 3). Lysosomes are crucial for the degradation of substrates from the cytoplasm, as well as 27 membrane bound compartments derived from the secretory, endocytic, autophagic and 28 phagocytic pathways. The limiting membrane of lysosomes is lined with so-called lysosomal 29 membrane glycoproteins (LAMPs) that are comprised of a short cytoplasmic domain, a single 30 transmembrane span, and a highly, N- and O-glycosylated lumenal domain (4-6).
    [Show full text]
  • Sensitization to the Lysosomal Cell Death Pathway by Oncogene- Induced Down-Regulation of Lysosome-Associated Membrane Proteins 1 and 2
    Research Article Sensitization to the Lysosomal Cell Death Pathway by Oncogene- Induced Down-regulation of Lysosome-Associated Membrane Proteins 1 and 2 Nicole Fehrenbacher,1 Lone Bastholm,2 Thomas Kirkegaard-Sørensen,1 Bo Rafn,1 Trine Bøttzauw,1 Christina Nielsen,1 Ekkehard Weber,3 Senji Shirasawa,4 Tuula Kallunki,1 and Marja Ja¨a¨ttela¨1 1Apoptosis Department and Centre for Genotoxic Stress Response, Institute for Cancer Biology, Danish Cancer Society; 2Institute of Molecular Pathology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 3Institute of Physiological Chemistry, Medical Faculty, Martin-Luther-University Halle-Wittenberg, Halle, Germany; and 4Department of Cell Biology, School of Medicine, Fukuoka University, Fukuoka, Japan Abstract molecules of the cell to breakdown products available for Expression and activity of lysosomal cysteine cathepsins metabolic reuse (3, 4). Cathepsin proteases are among the best- correlate with the metastatic capacity and aggressiveness of studied lysosomal hydrolases. They are maximally active at the tumors. Here, we show that transformation of murine acidic pH of lysosomes (pH 4–5). However, many of them can be Y527F embryonic fibroblasts with v-H-ras or c-src changes the active at the neutral pH outside lysosomes, albeit with a decreased distribution, density, and ultrastructure of the lysosomes, efficacy and/or altered specificity (5). For example, transformation and tumor environment enhance the expression of lysosomal decreases the levels of lysosome-associated membrane pro- teins (LAMP-1 and LAMP-2) in an extracellular signal- cysteine cathepsins and increase their secretion into the extracel- regulated kinase (ERK)- and cathepsin-dependent manner, lular space (6). Once outside the tumor cells, cathepsins stimulate and sensitizes the cells to lysosomal cell death pathways angiogenesis, tumor growth, and invasion in murine cancer induced by various anticancer drugs (i.e., cisplatin, etoposide, models, thereby enhancing cancer progression (7, 8).
    [Show full text]
  • Adenovirus Infections in Humans
    CHAPTER 11 Adenovirus Infections in Humans STEPHEN E. STRAUS I. INTRODUCTION Adenoviruses are ubiquitous agents that infect humans of all ages. The discovery of the first adenovirus types three decades ago paved the way for countless studies that continue to uncover additional viral strains and ever expand our comprehension of their significance to man. Whereas some human adenoviruses are being examined at the increasingly so­ phisticated molecular and cellular levels, the means by which they infect man, provoke illness, or are handled by the body's immune system remain very poorly understood. This chapter represents an attempt to catalogue the known human adenovirus agents, to summarize the data pertaining to their acquisition and transmission, to review the range of illness with which they are associated, and to highlight those aspects of adenovirus infection that are in need of further investigation. II. ADENOVIRUSES RECOVERED FROM HUMANS The 41 distinct adenovirus types that have been recovered from hu­ mans thus far are listed in Table I. Most of these agents were isolated during an extremely fruitful decade of studies that followed the initial discovery of adenoviruses. A wide range of illnesses has been associated with the better-defined, lower-numbered virus types, but the predilection STEPHEN E. STRAUS • Medical Virology Section, Laboratory of Clinical Investigation, National Institutes of Health, Bethesda, Maryland 20205. 451 H. S. Ginsberg (ed.), The Adenoviruses © Plenum Press, New York 1984 452 STEPHEN E. STRAUS TABLE I. Adenovirus ImmunotypesQ Major Prototype associated Type strain Source Patient diagnosis diseasesb Ad71 Adenoid Hypertrophied tonsils and Respiratory adenoids 2 Ad6 Adenoid Hypertrophied tonsils and Respiratory adenoids 3 G.B.
    [Show full text]
  • Supporting Information
    Supporting Information Rosenberg et al. 10.1073/pnas.1307243110 SI Results and Discussion domestic ungulates (horses, cows, sheep, goats, camels, and pigs) Of the 83 arboviruses, nonhuman vertebrate hosts have been and rodents in both groups might be a consequence of spatial identified for 70 (84%); the remaining 13 are presumed to be proximity to humans. Sentinel monkeys were often used in pro- zoonoses because there is no indication they can be transmitted cedures to isolate arboviruses, which might account for their directly between humans by vectors (Table S1). Animal hosts have higher representation among arboviruses. In contrast, there are been identified for at least 57 (44%) of the 130 nonarboviruses; an few published records of bats being routinely sampled during additional 5 (8%) are presumed on epidemiological evidence to arbovirus studies, and only two arboviruses (3%) have been iso- have nonhuman reservoirs (Table S1). A number of viruses infect lated from bats. The reason a much larger number of arbovirus more than one nonhuman vertebrate host species and it is likely species (n = 16) have been isolated from birds than have that the variety of hosts is wider than has been recorded. The nonarbovirus species (n = 1) might, however, be characteristic of predominant host groups for arboviruses (n = 70) are nonhuman the pathogenicity of the togaviruses and flaviviruses, which are primates (31%), rodents (29%), ungulates (26%), and birds (23%); much more common among the arboviruses. The most prominent for the nonarboviruses (n = 57), they are rodents (30%), ungu- vectors of arboviruses were mosquitoes (67%), ticks (19%), and lates (26%), bats (23%), and primates (16%).
    [Show full text]
  • Dipeptidase Aminodipeptidase, Quiescent Cell Proline of a Novel
    Vesicular Localization and Characterization of a Novel Post-Proline-Cleaving Aminodipeptidase, Quiescent Cell Proline Dipeptidase This information is current as of September 26, 2021. Murali Chiravuri, Fernando Agarraberes, Suzanne L. Mathieu, Henry Lee and Brigitte T. Huber J Immunol 2000; 165:5695-5702; ; doi: 10.4049/jimmunol.165.10.5695 http://www.jimmunol.org/content/165/10/5695 Downloaded from References This article cites 28 articles, 18 of which you can access for free at: http://www.jimmunol.org/content/165/10/5695.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Vesicular Localization and Characterization of a Novel Post-Proline-Cleaving Aminodipeptidase, Quiescent Cell Proline Dipeptidase1 Murali Chiravuri,* Fernando Agarraberes,† Suzanne L. Mathieu,* Henry Lee,* and Brigitte T. Huber2* A large number of chemokines, cytokines, and signal peptides share a highly conserved X-Pro motif on the N-terminus.
    [Show full text]
  • Fluid Biomarkers in Frontotemporal Dementia: Past, Present and Future
    Neurodegeneration J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-323520 on 13 November 2020. Downloaded from Review Fluid biomarkers in frontotemporal dementia: past, present and future Imogen Joanna Swift ,1 Aitana Sogorb- Esteve,1,2 Carolin Heller ,1 Matthis Synofzik,3,4 Markus Otto ,5 Caroline Graff,6,7 Daniela Galimberti ,8,9 Emily Todd,2 Amanda J Heslegrave,1 Emma Louise van der Ende ,10 John Cornelis Van Swieten ,10 Henrik Zetterberg,1,11 Jonathan Daniel Rohrer 2 ► Additional material is ABSTRACT into a behavioural form (behavioural variant fron- published online only. To view, The frontotemporal dementia (FTD) spectrum of totemporal dementia (bvFTD)), a language variant please visit the journal online (primary progressive aphasia (PPA)) and a motor (http:// dx. doi. org/ 10. 1136/ neurodegenerative disorders includes a heterogeneous jnnp- 2020- 323520). group of conditions. However, following on from a series presentation (either FTD with amyotrophic lateral of important molecular studies in the early 2000s, major sclerosis (FTD- ALS) or an atypical parkinsonian For numbered affiliations see advances have now been made in the understanding disorder). Neuroanatomically, the FTD spectrum end of article. of the pathological and genetic underpinnings of the is characteristically associated with dysfunction and disease. In turn, alongside the development of novel neuronal loss in the frontal and temporal lobes, but Correspondence to more widespread cortical, subcortical, cerebellar Dr Jonathan Daniel Rohrer, methodologies for measuring proteins and other Dementia Research molecules in biological fluids, the last 10 years have and brainstem involvement is now recognised. Centre, Department of seen a huge increase in biomarker studies within FTD.
    [Show full text]