Lessons from Immune Responses and Vaccines Against Murine
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Identification of an Overprinting Gene in Merkel Cell Polyomavirus Provides Evolutionary Insight Into the Birth of Viral Genes
Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes Joseph J. Cartera,b,1,2, Matthew D. Daughertyc,1, Xiaojie Qia, Anjali Bheda-Malgea,3, Gregory C. Wipfa, Kristin Robinsona, Ann Romana, Harmit S. Malikc,d, and Denise A. Gallowaya,b,2 Divisions of aHuman Biology, bPublic Health Sciences, and cBasic Sciences and dHoward Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 Edited by Peter M. Howley, Harvard Medical School, Boston, MA, and approved June 17, 2013 (received for review February 24, 2013) Many viruses use overprinting (alternate reading frame utiliza- mammals and birds (7, 8). Polyomaviruses leverage alternative tion) as a means to increase protein diversity in genomes severely splicing of the early region (ER) of the genome to generate pro- constrained by size. However, the evolutionary steps that facili- tein diversity, including the large and small T antigens (LT and ST, tate the de novo generation of a novel protein within an ancestral respectively) and the middle T antigen (MT) of murine poly- ORF have remained poorly characterized. Here, we describe the omavirus (MPyV), which is generated by a novel splicing event and identification of an overprinting gene, expressed from an Alter- overprinting of the second exon of LT. Some polyomaviruses can nate frame of the Large T Open reading frame (ALTO) in the early drive tumorigenicity, and gene products from the ER, especially region of Merkel cell polyomavirus (MCPyV), the causative agent SV40 LT and MPyV MT, have been extraordinarily useful models of most Merkel cell carcinomas. -
The Polyomavirus Major Capsid Protein VP1 Interacts with the Nuclear Matrix Regulatory Protein
FEBS 23316 FEBS Letters 467 (2000) 359^364 View metadata, citation and similar papers at core.ac.uk brought to you by CORE The polyomavirus major capsid protein VP1 interacts with theprovided nuclearby Elsevier - Publisher Connector matrix regulatory protein YY1 Zdena Palkova¨a;b, Hana Sípanielova¨b, Vanesa Gottifredia;1, Dana Hollanderova¨b, Jitka Forstova¨b, Paolo Amatia;* aInstituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Universita© di Roma La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy bDepartment of Genetics and Microbiology, Faculty of Natural Sciences, Charles University, Vinie©na¨ 5, 12844 Prague 2, Czech Republic Received 17 December 1999 Edited by Hans-Dieter Klenk The external loops are likely to be the structures involved in Abstract Polyomavirus reaches the nucleus in a still encapsi- dated form, and the viral genome is readily found in association cell receptor recognition by virions [4] and, therefore, to be with the nuclear matrix. This association is thought to be the main antigenic determinants. The £exible C-terminal arms essential for viral replication. In order to identify the protein(s) form interpentameric contacts and the basic amino acids of involved in the virus-nuclear matrix interaction, we focused on the N terminal arm are responsible for the non-speci¢c DNA- the possible roles exerted by the multifunctional cellular nuclear binding activity of VP1 [6,7]. matrix protein Yin Yang 1 (YY1) and by the viral major capsid The necessity for viral genomes to associate to the nuclear protein VP1. In the present work we report on the in vivo matrix (NM) in order to be expressed, has been demonstrated association between YY1 and VP1. -
Cryptic Inoviruses Revealed As Pervasive in Bacteria and Archaea Across Earth’S Biomes
ARTICLES https://doi.org/10.1038/s41564-019-0510-x Corrected: Author Correction Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes Simon Roux 1*, Mart Krupovic 2, Rebecca A. Daly3, Adair L. Borges4, Stephen Nayfach1, Frederik Schulz 1, Allison Sharrar5, Paula B. Matheus Carnevali 5, Jan-Fang Cheng1, Natalia N. Ivanova 1, Joseph Bondy-Denomy4,6, Kelly C. Wrighton3, Tanja Woyke 1, Axel Visel 1, Nikos C. Kyrpides1 and Emiley A. Eloe-Fadrosh 1* Bacteriophages from the Inoviridae family (inoviruses) are characterized by their unique morphology, genome content and infection cycle. One of the most striking features of inoviruses is their ability to establish a chronic infection whereby the viral genome resides within the cell in either an exclusively episomal state or integrated into the host chromosome and virions are continuously released without killing the host. To date, a relatively small number of inovirus isolates have been extensively studied, either for biotechnological applications, such as phage display, or because of their effect on the toxicity of known bacterial pathogens including Vibrio cholerae and Neisseria meningitidis. Here, we show that the current 56 members of the Inoviridae family represent a minute fraction of a highly diverse group of inoviruses. Using a machine learning approach lever- aging a combination of marker gene and genome features, we identified 10,295 inovirus-like sequences from microbial genomes and metagenomes. Collectively, our results call for reclassification of the current Inoviridae family into a viral order including six distinct proposed families associated with nearly all bacterial phyla across virtually every ecosystem. -
SV40 Large T Antigen Targets Multiple Cellular Pathways to Elicit Cellular Transformation
Oncogene (2005) 24, 7729–7745 & 2005 Nature Publishing Group All rights reserved 0950-9232/05 $30.00 www.nature.com/onc SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation Deepika Ahuja1,2, M Teresa Sa´ enz-Robles1,2 and James M Pipas*,1 1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA DNA tumor viruses such as simian virus 40 (SV40) three proteins that are structural components of the express dominant acting oncoproteins that exert their virion (VP1, VP2, VP3) and two nonstructural proteins effects by associating with key cellular targets and termed large T antigen (T antigen) and small T antigen altering the signaling pathways they govern. Thus, tumor (t antigen). In addition, some members of the Polyoma- viruses have proved to be invaluable aids in identifying viridae encode additional proteins that are virus specific proteins that participate in tumorigenesis, and in under- or are encoded by a subset of viruses in the family. For standing the molecular basis for the transformed pheno- example, SV40 encodes three such proteins: agnopro- type. The roles played by the SV40-encoded 708 amino- tein, 17K T, and small leader protein. The genomes of acid large T antigen (T antigen), and 174 amino acid small all polyomaviruses can be divided into three elements: T antigen (t antigen), in transformation have been an early coding unit, a late coding unit, and a regulatory examined extensively. These studies have firmly estab- region (Figure 1). In a productive infection, expression lished that large T antigen’s inhibition of the p53 and Rb- of the early coding unit is effected by the cellular family of tumor suppressors and small T antigen’s action transcription apparatus and results in expression of the on the pp2A phosphatase, are important for SV40-induced large, small and 17K T antigens. -
Newly Discovered KI, WU, and Merkel Cell Polyomaviruses
Sadeghi et al. Virology Journal 2010, 7:251 http://www.virologyj.com/content/7/1/251 RESEARCH Open Access Newly discovered KI, WU, and Merkel cell polyomaviruses: No evidence of mother-to-fetus transmission Mohammadreza Sadeghi1, Anita Riipinen2, Elina Väisänen1, Tingting Chen1, Kalle Kantola1, Heljä-Marja Surcel3, Riitta Karikoski4, Helena Taskinen2,5, Maria Söderlund-Venermo1, Klaus Hedman1,6* Abstract Background: Three* human polyomaviruses have been discovered recently, KIPyV, WUPyV and MCPyV. These viruses appear to circulate ubiquitously; however, their clinical significance beyond Merkel cell carcinoma is almost completely unknown. In particular, nothing is known about their preponderance in vertical transmission. The aim of this study was to investigate the frequency of fetal infections by these viruses. We sought the three by PCR, and MCPyV also by real-time quantitative PCR (qPCR), from 535 fetal autopsy samples (heart, liver, placenta) from intrauterine fetal deaths (IUFDs) (N = 169), miscarriages (120) or induced abortions (246). We also measured the MCPyV IgG antibodies in the corresponding maternal sera (N = 462) mostly from the first trimester. Results: No sample showed KIPyV or WUPyV DNA. Interestingly, one placenta was reproducibly PCR positive for MCPyV. Among the 462 corresponding pregnant women, 212 (45.9%) were MCPyV IgG seropositive. Conclusions: Our data suggest that none of the three emerging polyomaviruses often cause miscarriages or IUFDs, nor are they transmitted to fetuses. Yet, more than half the expectant mothers were susceptible to infection by the MCPyV. Background tumorigenic MCPyV [5], also found in the nasopharynx Among the five* human polymaviruses known, aside [13-15], the mode of transmission and, host cells, as from the BK virus (BKV) and JC virus (JCV) [1,2], well as latency characteristics are yet to be established. -
Opportunistic Intruders: How Viruses Orchestrate ER Functions to Infect Cells
REVIEWS Opportunistic intruders: how viruses orchestrate ER functions to infect cells Madhu Sudhan Ravindran*, Parikshit Bagchi*, Corey Nathaniel Cunningham and Billy Tsai Abstract | Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co‑opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus–ER interactions has become available, these insights may lead to the development of crucial therapeutic agents. Morphogenesis Viruses have evolved sophisticated strategies to establish The ER is a membranous system consisting of the The process by which a virus infection. Some viruses bind to cellular receptors and outer nuclear envelope that is contiguous with an intri‑ particle changes its shape and initiate entry, whereas others hijack cellular factors that cate network of tubules and sheets1, which are shaped by structure. disassemble the virus particle to facilitate entry. After resident factors in the ER2–4. The morphology of the ER SEC61 translocation delivering the viral genetic material into the host cell and is highly dynamic and experiences constant structural channel the translation of the viral genes, the resulting proteins rearrangements, enabling the ER to carry out a myriad An endoplasmic reticulum either become part of a new virus particle (or particles) of functions5. -
Receptor-Binding and Oncogenic Properties of Polyoma Viruses Isolated from Feral Mice
Receptor-Binding and Oncogenic Properties of Polyoma Viruses Isolated from Feral Mice John Carroll1[, Dilip Dey1[, Lori Kreisman1[, Palanivel Velupillai1, Jean Dahl1, Samuel Telford2, Roderick Bronson1, Thomas Benjamin1* 1 Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts, United States of America Laboratory strains of the mouse polyoma virus differ markedly in their abilities to replicate and induce tumors in newborn mice. Major determinants of pathogenicity lie in the sialic binding pocket of the major capsid protein Vp1 and dictate receptor-binding properties of the virus. Substitutions at two sites in Vp1 define three prototype strains, which vary greatly in pathogenicity. These strains replicate in a limited fashion and induce few or no tumors, cause a disseminated infection leading to the development of multiple solid tumors, or replicate and spread acutely causing early death. This investigation was undertaken to determine the Vp1 type(s) of new virus isolates from naturally infected mice. Compared with laboratory strains, truly wild-type viruses are constrained with respect to their selectivity and avidity of binding to cell receptors. Fifteen of 15 new isolates carried the Vp1 type identical to that of highly tumorigenic laboratory strains. Upon injection into newborn laboratory mice, the new isolates induced a broad spectrum of tumors, including ones of epithelial as well as mesenchymal origin. Though invariant in their Vp1 coding sequences, these isolates showed considerable variation in their regulatory sequences. The common Vp1 type has two essential features: 1) failure to recognize ‘‘pseudoreceptors’’ with branched chain sialic acids binding to which would attenuate virus spread, and 2) maintenance of a hydrophobic contact with true receptors bearing a single sialic acid, which retards virus spread and avoids acute and potentially lethal infection of the host. -
REVIEW Hepatitis C Virus
DOI:http://dx.doi.org/10.7314/APJCP.2012.13.12.5917 Hepatitis C Virus -Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development REVIEW Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development Hossein Keyvani1, Mehdi Fazlalipour2*, Seyed Hamid Reza Monavari1, Hamid Reza Mollaie2 Abstract Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. -
Immunohistochemical Detection of KI Polyomavirus in Lung and Spleen
Virology 468-470 (2014) 178–184 Contents lists available at ScienceDirect Virology journal homepage: www.elsevier.com/locate/yviro Immunohistochemical detection of KI polyomavirus in lung and spleen Erica A. Siebrasse 1,a, Nang L. Nguyen a,1, Colin Smith b, Peter Simmonds c, David Wang a,n a Washington University School of Medicine, Campus Box 8230, 660 S. Euclid Ave., St. Louis, MO 63110, USA b Department of Pathology, University of Edinburgh, Scotland, UK c Roslin Institute, University of Edinburgh, Scotland, UK article info abstract Article history: Little is known about the tissue tropism of KI polyomavirus (KIPyV), and there are no studies to date Received 23 April 2014 describing any specific cell types it infects. The limited knowledge of KIPyV tropism has hindered study of Returned to author for revisions this virus and understanding of its potential pathogenesis in humans. We describe tissues from two 28 July 2014 immunocompromised patients that stained positive for KIPyV antigen using a newly developed immuno- Accepted 5 August 2014 histochemical assay targeting the KIPyV VP1 (KVP1) capsid protein. In the first patient, a pediatric bone Available online 3 September 2014 marrow transplant recipient, KVP1 was detected in lung tissue. Double immunohistochemical staining Keywords: demonstrated that approximately 50% of the KVP1-positive cells were CD68-positive cells of the macro- KI polyomavirus phage/monocyte lineage. In the second case, an HIV-positive patient, KVP1 was detected in spleen and lung Tissue tropism tissues. These results provide the first identification of a specific cell type in which KVP1 can be detected and Immunohistochemistry expand our understanding of basic properties and in vivo tropism of KIPyV. -
Chimeric Murine Polyomavirus Virus-Like Particles Induce Plasmodium Antigen-Specific CD8+ T Cell and Antibody Responses
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by ResearchOnline at James Cook University ORIGINAL RESEARCH published: 19 June 2019 doi: 10.3389/fcimb.2019.00215 Chimeric Murine Polyomavirus Virus-Like Particles Induce Plasmodium Antigen-Specific CD8+ T Cell and Antibody Responses David J. Pattinson 1,2*, Simon H. Apte 1, Nani Wibowo 3, Yap P. Chuan 3, Tania Rivera-Hernandez 3, Penny L. Groves 1, Linda H. Lua 4, Anton P. J. Middelberg 3 and Denise L. Doolan 1,2* 1 Infectious Diseases Programme, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia, 2 Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia, 3 Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, Australia, 4 Protein Expression Facility, University of Queensland, Brisbane, QLD, Australia Edited by: An effective vaccine against the Plasmodium parasite is likely to require the induction Alberto Moreno, Emory University School of Medicine, of robust antibody and T cell responses. Chimeric virus-like particles are an effective United States vaccine platform for induction of antibody responses, but their capacity to induce Reviewed by: robust cellular responses and cell-mediated protection against pathogen challenge has Giampietro Corradin, Université de Lausanne, Switzerland not been established. To evaluate this, we produced chimeric constructs using the + + Kai Huang, murine polyomavirus structural protein with surface-exposed CD8 or CD4 T cell or University of Texas Medical Branch at B cell repeat epitopes derived from the Plasmodium yoelii circumsporozoite protein, and Galveston, United States + Sean C. -
Gene Regulation and Quality Control in Murine Polyomavirus Infection
viruses Review Gene Regulation and Quality Control in Murine Polyomavirus Infection Gordon G. Carmichael Department of Genetics and Genome Sciences, UCONN Health, Farmington, CT 06030, USA; [email protected]; Tel.: +1-860-679-2259 Academic Editors: J. Robert Hogg and Karen L. Beemon Received: 19 September 2016; Accepted: 11 October 2016; Published: 17 October 2016 Abstract: Murine polyomavirus (MPyV) infects mouse cells and is highly oncogenic in immunocompromised hosts and in other rodents. Its genome is a small, circular DNA molecule of just over 5000 base pairs and it encodes only seven polypeptides. While seemingly simply organized, this virus has adopted an unusual genome structure and some unusual uses of cellular quality control pathways that, together, allow an amazingly complex and varied pattern of gene regulation. In this review we discuss how MPyV leverages these various pathways to control its life cycle. Keywords: quality control; transcription; RNA decay; RNA editing; nuclear retention 1. The Virus Murine polyomavirus (MPyV) is highly oncogenic in rodents and has a small circular double-stranded DNA (dsDNA) genome of about 5300 base pairs. The genome is divided into “early” and “late” regions, which are expressed and regulated differently as infection proceeds (Figure1)[ 1–4]. The early and late transcription units extend in opposite directions around the circular genome from start sites near the bidirectional origin of DNA replication [2,5]. Primary RNA products from the early transcription unit are alternatively spliced to yield four early mRNAs which encode the large T antigen (100 kDa), the middle T antigen (56 kDa), the small T antigen (22 kDa) and the tiny T antigen (10 kDa) [6]. -
The Mirna World of Polyomaviruses Ole Lagatie1*, Luc Tritsmans2 and Lieven J Stuyver1
Lagatie et al. Virology Journal 2013, 10:268 http://www.virologyj.com/content/10/1/268 REVIEW Open Access The miRNA world of polyomaviruses Ole Lagatie1*, Luc Tritsmans2 and Lieven J Stuyver1 Abstract Polyomaviruses are a family of non-enveloped DNA viruses infecting several species, including humans, primates, birds, rodents, bats, horse, cattle, raccoon and sea lion. They typically cause asymptomatic infection and establish latency but can be reactivated under certain conditions causing severe diseases. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in several cellular processes by binding to and inhibiting the translation of specific mRNA transcripts. In this review, we summarize the current knowledge of microRNAs involved in polyomavirus infection. We review in detail the different viral miRNAs that have been discovered and the role they play in controlling both host and viral protein expression. We also give an overview of the current understanding on how host miRNAs may function in controlling polyomavirus replication, immune evasion and pathogenesis. Keywords: Polyomaviruses, microRNAs, Virus-host interaction, Immune evasion Review for BKPyV, Merkel cell carcinoma (MCC) for Merkel General overview of polyomaviruses Cell Virus (MCPyV) and trichodysplasia spinulosa for Polyomaviruses comprise a family of DNA tumor vi- Trichodysplasia spinulosa-associated Polyomavirus (TSPyV) ruses. They are non-enveloped and have a circular, [4,10,11,14-20]. One of the most striking observations is the double stranded DNA genome of around 5,100 bp [1]. fact that asymptomatic infection occurs during childhood The virion consists of 72 pentamers of the capsid pro- which is followed ordinarily by life-long asymptomatic tein VP1 with a single copy of VP2 and VP3 associated persistence [21].