DOCSLIB.ORG

Mcewan, William (2010) Factors Affecting Replication and Cross-Species Transmission of Feline Immunodeficiency Virus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mcewan, William (2010) Factors Affecting Replication and Cross-Species Transmission of Feline Immunodeficiency Virus McEwan, William (2010) Factors affecting replication and cross-species transmission of feline immunodeficiency virus. PhD thesis. http://theses.gla.ac.uk/1388/ Copyright and moral rights for this thesis are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Glasgow Theses Service http://theses.gla.ac.uk/ [email protected] Factors affecting replication and cross-species transmission of feline immunodeficiency virus Submitted in fulfilment of the requirements of the degree of DOCTOR OF PHILOSOPHY by William McEwan, B.Sc., M.Res. Institute of Comparative Medicine Faculty of Veterinary Medicine University of Glasgow September 2009 Abstract In order to successfully invade a new species, lentiviruses must overcome restriction factors, dominant blocks to replication, and be able to make use of available host factors such as entry receptors for replication. Human immunodeficiency virus (HIV-1) infection is blocked at a post-entry stage by rhesus macaque TRIM5α, an effect that is enhanced by host factor cyclophilin A (CypA), but largely evades restriction by the human TRIM5α variant. HIV-1 replication is also inhibited by simian APOBEC3G but is able to evade restriction by human APOBEC3G by inducing its degradation through expression of accessory protein Vif. Viral entry and tissue tropism are determined by an interaction of the viral Env glycoprotein with a cell surface receptor and a seven transmembrane domain co-receptor. The feline immunodeficiency virus (FIV) infects diverse felid species including the African lion, where infection has likely been endemic since at least the late Pleistocene, and the domestic cat, a more recent host. For domestic cat strains of FIV (FIV-Fca), entry is mediated by host proteins CD134 and CXCR4, but the identity of receptors in non-domestic strains of FIV is unknown. This thesis demonstrates that two strains of FIV isolated from lions (FIV-Ple subtypes B and E) differ in their receptor tropism and that subtype E shares entry receptors with FIV-Fca. The findings suggest that alternative receptor usage is a strategy employed by FIV in this species and has implications for the disputed pathology and tissue tropism of infection in African lions. Next, we tested the hypothesis that species which have harboured lentiviral infection for a long time are better able to prevent viral replication than recent hosts. Whilst we found that TRIM5α is non-functional in all felid species tested, evidence of potent APOBEC3 activity was found and, in lion cells, potently restricts production of infectious FIV. Moreover, lion primary T-cells prevent 2 replication of diverse FIV strains and restrict primate lentiviruses at post-entry stages, suggesting that co-evolution with lentiviruses has driven the selection of broad-ranging restriction factors. Structural and biophysical analyses suggest that whilst FIV’s interaction with CypA appears to be conserved in affinity with HIV-1, the interaction does not appear to be crucial for replication and, in the absence of restriction by TRIM5α, the role of the capsid-CypA interaction is discussed. Overall the study explains the permissivity of domestic cat cells to retroviral infection and identifies FIV infection of lions as an example of host adaptation driven by current lentiviral infection. 3 4 Table of Contents Abstract ............................................................................... 2 Table of Contents .......................................................................... 5 List of Tables and Figures ................................................................ 10 List of Abbreviations ...................................................................... 13 Acknowledgements ........................................................................ 17 Chapter 1. Introduction ............................................................... 18 1.1 Preface ......................................................................... 18 1.2 Retroviruses .................................................................... 19 1.3 Cross-species transmission of lentiviruses in the primates and felids . 23 1.4 Lentiviral entry ................................................................ 26 1.4.1 Receptors for HIV-1 entry .................................................... 26 1.4.2 Molecular mechanism of HIV-1 entry ....................................... 27 1.4.3 Variable tropism of HIV-1 .................................................... 28 1.4.4 Receptors for FIV-Fca entry ................................................. 30 1.4.5 Receptor tropism of non-domestic cat FIV ................................ 33 1.5 Post-entry restriction ......................................................... 34 1.5.1 Murine Fv 1 system ............................................................ 35 1.5.2 TRIM5α restriction ............................................................ 36 1.5.3 Virus interaction maps to TRIM5 B30.2 or CypA domain ................ 37 1.5.4 Adaptive evolution of TRIM5α ............................................... 40 1.5.5 Contribution of RBCC domain to restriction .............................. 42 1.6 The role of Cyclophilin A in lentiviral replication ........................ 46 1.6.1 Cyclophilin A and its inhibitors.............................................. 46 1.6.2 CypA is a cofactor of HIV-1 replication .................................... 47 1.6.3 CypA can have alternative effects on lentiviral replication ............ 48 1.7 Induction of hypermutation by APOBEC3 .................................. 50 1.7.1 Discovery of human APOBEC3G ............................................. 50 5 1.7.2 Antiviral activity of human APOBEC3G ..................................... 51 1.7.3 Encapsidation of human APOBEC3G ........................................ 53 1.7.4 Antiviral activity of other human APOBEC3 genes ....................... 54 1.7.5 The role of Vif in overcoming APOBEC3G and 3F restriction ........... 55 1.7.6 Positive selection of APOBECs ............................................... 56 1.7.7 An expanded cluster of feline APOBEC3 genes ........................... 57 1.7.8 Vif of Feline Immunodeficiency Virus ...................................... 59 1.8 Scope of this thesis ........................................................... 59 Chapter 2. Materials and Methods ................................................... 61 2.1 Molecular cloning ............................................................. 61 2.1.1 Nucleic acid extraction and PCR ............................................ 61 2.1.2 Cloning techniques ............................................................ 62 2.1.3 Sequencing of DNA ............................................................ 63 2.1.4 FIV Envelopes .................................................................. 63 2.1.5 CD134 and CXCR4 ............................................................. 64 2.1.6 TRIM5 ........................................................................... 64 2.1.7 Capsid and cyclophilin A ..................................................... 65 2.1.8 APOBEC3 and vif .............................................................. 66 2.2 Cells and viruses .............................................................. 67 2.2.1 Adherent cells ................................................................. 67 2.2.2 Suspension cells ............................................................... 67 2.2.3 Primary T-cells ................................................................ 68 2.2.4 Replication-competent FIV .................................................. 69 2.2.5 Tissue culture infection with replication competent FIV ............... 70 2.2.6 Drugs and inhibitors .......................................................... 71 2.2.7 Stable transduction of cell lines ............................................ 72 2.2.8 Pseudotype production ....................................................... 73 2.2.9 Pseudotype assay ............................................................. 75 2.2.10 RNA interference ............................................................ 77 6 2.3 Quantitative techniques and immunoloblotting .......................... 78 2.3.1 p24 ELISA ....................................................................... 78 2.3.2 Quantification of reverse transcriptase activity .......................... 78 2.3.3 Real-time PCR ................................................................. 79 2.3.4 SDS-PAGE & Immunoblotting ................................................ 79 2.3.5 Far western blot .............................................................. 80 2.4 Biophysical and structural techniques ..................................... 81 2.4.1 Recombinant protein purification .......................................... 81 2.4.2 Isothermal Titration Calorimetry ........................................... 83 2.4.3 X-ray crystallography ......................................................... 84 2.5 In silico techniques ..........................................................
Load more

Recommended publications
  • Common Modular Structure of Lentivirus Ltrs
    VIROLOGY 224, 256–267 (1996) ARTICLE NO. 0527 Common Modular Structure of Lentivirus LTRs View metadata, citation and similar papers at core.ac.uk brought to you by CORE KORNELIE FRECH,* RUTH BRACK-WERNER,*,† and THOMAS WERNER*,1 provided by Elsevier - Publisher Connector *Institut fu¨rSa¨ugetiergenetik and †Institut fu¨r Molekulare Virologie, GSF-Forschungszentrum fu¨r Umwelt und Gesundheit GmbH, Ingolsta¨dter Landstrasse 1, D-85758 Oberschleißheim, Germany Received April 17, 1996; accepted August 5, 1996 Retroviruses are expressed under the control of viral control regions designated long terminal repeats (LTRs), which contain all signals for transcriptional initiation as well as transcriptional termination. However, retroviral LTRs from different species within a common genus, such as Lentivirus, do not show significant overall sequence homology. We compiled a model of the functional organization of 20 Lentivirus LTRs which we show to recognize all known Lentivirus LTRs. To this end we combined our previously published methods for identification of transcription elements with secondary structure element analysis in a novel modular approach. We deduced descriptions for three new Lentivirus-specific sequence elements present in most of the Lentivirus LTRs but absent in LTRs of other retrovirus families (B, C, D-type, BLV-HTLV, Spuma). Four of the 10 elements defined in our study were primate-specific. We were able to deduce a phylogeny based on our model which agrees in general with the phylogeny derived from the polymerase genes of these viruses. Our model indicated that more than 100 LTRs from the databases are of Lentivirus origin and can be clearly separated from all other LTR types (B, C, D, BLV-HTLV, Spuma).
    [Show full text]
  • Emerging Viruses in the Felidae: Shifting Paradigms
    Viruses 2012, 4, 236-257; doi:10.3390/v4020236 OPEN ACCESS viruses ISSN 1999-4915 www.mdpi.com/journal/viruses Review Emerging Viruses in the Felidae: Shifting Paradigms Stephen J. O’Brien 1,*,†, Jennifer L. Troyer 2, Meredith A. Brown 3, Warren E. Johnson 1, Agostinho Antunes 4, Melody E. Roelke 2 and Jill Pecon-Slattery 1 1 Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD 21702, USA; E-Mails: [email protected] (W.E.J.); [email protected] (J.P.-S.) 2 SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USA; E-Mails: [email protected] (J.L.T.); [email protected] (M.E.R.) 3 Banfield Pet Hospital, 800 NE Tillamook Street, Portland, OR 97213, USA; E-Mail: [email protected] 4 CIMAR/CIIMAR, University of Porto, Rua dos Bragas, 177, Porto 4050-123, Portugal; E-Mail: [email protected] † Present Address: Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg University, St. Petersburg, 190000, Russia. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-240-446-1021; Fax: +1-301-662-1413. Received: 1 December 2011; in revised form: 21 December 2011 / Accepted: 11 January 2012 / Published: 7 February 2012 Abstract: The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species.
    [Show full text]
  • Evolution of Puma Lentivirus in Bobcats (Lynx Rufus) and Mountain Lions (Puma Concolor) in North America Justin S
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln USDA National Wildlife Research Center - Staff U.S. Department of Agriculture: Animal and Plant Publications Health Inspection Service 2014 Evolution of Puma Lentivirus in Bobcats (Lynx rufus) and Mountain Lions (Puma concolor) in North America Justin S. Lee Colorado State University, [email protected] Sarah N. Bevins USDA National Wildlife Research Center, [email protected] Laurel E. K. Serleys University of California, Los Angeles, [email protected] Winston Vickers University of California, Davis, [email protected] Ken A. Logan Colorado Parks and Wildlife, [email protected] See next page for additional authors Follow this and additional works at: https://digitalcommons.unl.edu/icwdm_usdanwrc Part of the Life Sciences Commons Lee, Justin S.; Bevins, Sarah N.; Serleys, Laurel E. K.; Vickers, Winston; Logan, Ken A.; Aldredge, Mat; Boydston, Erin E.; Lyren, Lisa M.; McBride, Roy; Roelke-Parker, Melody; Pecon-Slattery, Jill; Troyer, Jennifer L.; Riley, Seth P.; Boyce, Walter M.; Crooks, Kevin R.; and VandeWoude, Sue, "Evolution of Puma Lentivirus in Bobcats (Lynx rufus) and Mountain Lions (Puma concolor) in North America" (2014). USDA National Wildlife Research Center - Staff Publications. 1534. https://digitalcommons.unl.edu/icwdm_usdanwrc/1534 This Article is brought to you for free and open access by the U.S. Department of Agriculture: Animal and Plant Health Inspection Service at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in USDA National Wildlife Research Center - Staff ubP lications by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Justin S. Lee, Sarah N.
    [Show full text]
  • Assessment and Analysis of the Restriction of Retroviral Infection by the Murine APOBEC3 Protein
    Assessment and Analysis of the Restriction of Retroviral Infection by the Murine APOBEC3 Protein Halil Aydin Thesis submitted to the Faculty of Graduate and Postdoctoral Studies of the University of Ottawa in partial fulfillment of the requirements for the degree of Masters of Science Department of Biochemistry, Microbiology and Immunology Faculty of Medicine ©Halil Aydin, Ottawa, Ontario, Canada, 2011 Learning the rules is hard work and lengthy but playing the game is exciting and fun. John Polanyi Nobel Prize Winner in Chemistry ii ABSTRACT Human APOBEC3 proteins are host-encoded intrinsic restriction factors that can prevent the replication of a broad range of human and animal retroviruses such as HIV, SIV, FIV, MLVs and XMRV. The main pathway of the restriction is believed to occur as a result of the cytidine deaminase activity of these proteins that converts cytidines into uridines in single- stranded DNA retroviral replication intermediates. Uridines in these DNA intermediates disrupt the viral replication cycle and also alter retrovirus infectivity because of the C-to-T transition mutations generated as a result of the deaminase activity on the minus strand DNA. In addition, human APOBEC3 proteins also exhibit a deamination-independent pathway to restrict retroviruses that is not currently well understood. Although the restriction of retroviruses by human APOBEC3 proteins has been intensely studied in vitro, our understanding of how the murine APOBEC3 (mA3) protein restricts retroviruses and/or prevents zoonotic infections in vivo is very limited. In contrast to humans and primates that have 7 APOBEC3 genes, mice have but a single copy. My study of the function and structure of mA3 revealed that it has an inverted functional organization for cytidine deamination in comparison to the human A3G catalytic sites.
    [Show full text]
  • Endogenous Retroviruses and the Immune System
    Endogenous Retroviruses and the Immune System George Robert Young Submitted to University College London in part fulfilment of the requirements for the degree of Doctor of Philosophy 2012 Division of Infection and Immunity Division of Immunoregulation University College London National Institute for Medical Research Gower Street The Ridgeway London London WC1E 6BT NW7 1AA 2 I, George Robert Young, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 3 Abstract ABSTRACT 4 Initial sequencing of the human and mouse genomes revealed that substantial fractions were composed of retroelements (REs) and endogenous retroviruses (ERVs), the latter being relics of ancestral retroviral infection. Further study revealed ERVs constitute up to 10% of many mammalian genomes. Despite this abundance, comparatively little is known about their interactions, beneficial or detrimental, with the host. This thesis details two distinct sets of interactions with the immune system. Firstly, the presentation of ERV-derived peptides to developing lymphocytes was shown to exert a control on the immune response to infection with Friend Virus (FV). A self peptide encoded by an ERV negatively selected a significant fraction of polyclonal FV- specific CD4+ T cells and resulted in an impaired immune response. However, CD4+ T cell-mediated antiviral activity was fully preserved and repertoire analysis revealed a deletional bias according to peptide affinity, resulting in an effective enrichment of high-affinity CD4+ T cells. Thus, ERVs exerted a significant influence on the immune response, a mechanism that may partially contribute to the heterogeneity seen in human immune responses to retroviral infections.
    [Show full text]
  • Contents Part 1 DNA TUMOR VIRUSES
    Contents Part 1 DNA TUMOR VIRUSES Symposium Participants V Foreword xvii Viral Oncogenes H. M. Temin Synopses Transforming Genes of DNA Tumor Viruses L. V. Crawford 9 Transforming Genes of Retroviruses P.H. Duesberg 13 DNA Tumor Viruses: Early RNAs and Early Proteins Transcription of the SV40 Genome in Virus-transformed Cells and Early Lytic Infection P. K. Ghosh, M. Piatak, V. B. Reddy, J. Swinscoe, P. Lebowitz, and S. M. Weissman 31 Regulation of SV40 Gene Expression through RNA Splicing G. Khoury, J. C. Alwine, R. Dhar, P. Gruss, C-J. Lai, S. Segal, and I. Seif 41 A Third Splice Site in SV40 Early mRNA D.F. Mark and P. Berg 55 Comparison of Polyoma Virus Transcription in Productively Infected Mouse Cells and Transformed Rodent Cell Lines R. Kamen, J. Favalom, J. Parker, R. Treisman, L. Lania, M. Fried, and A. Mellor 63 Transcription of SV40 DNA in Transformed Rat Cells M. Grigoryan, P. Chumakov, and E. Lukanidin 77 Expression of Transforming Viral Genes in Semipermissive Cells Transformed by SV40 or Adenovirus Type 2 or Type 5 S. J. Flint and G. A. Beltz 89 Catalytic Properties of the SV40 Large T Antigen R. Tfian, A. Robbins, and R. Clark 103 Enzymatic Activities Associated with the SV40 Large T Antigen J.D. Griffin, G. Spangler, and D. M. Livingston 113 DNA Binding and Sedimentation Properties of SV40 T Antigens Synthesized In Vivo and In Vitro C. Prives, Y. Beck, D. Gidoni, M. Oren, and it. Shure 123 Organization of T Antigens in the Polyoma Virus Genome T. Hunter, M.
    [Show full text]
  • Presence and Expression of Friend Erythroleukemia Virus-Related Sequences in Normal and Leukemic Mouse Tissues
    Proc. Natl. Acad. Sci. USA Vol. 76, No. 9, pp. 4455-4459, September 1979 Cell Biology Presence and expression of Friend erythroleukemia virus-related sequences in normal and leukemic mouse tissues (RNA tumor viruses/Friend spleen focus-forming virus/mechanism of transformation/differentiation/gene expression) ALAN BERNSTEIN, CATHERINE GAMBLE, DONNA PENROSE, AND TAK W. MAK The Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, 500 Sherbourne Street, Toronto, Ontario, Canada M4X 1K9 Communicated by J. Tuzo Wilson, May 22, 1979 ABSTRACT The nature and distribution of sequences re- Although the origin and nature of sarcoma virus-specific lated to the murine erythroleukemia virus, Friend spleen sequences have been well characterized, no comparable studies focus-forming virus (SFFV), have been analyzed by using a ra- have been reported on the rapidly transforming mammalian dioactive cDNA probe specific for the SFFV genome (cDNAsff). From the proportion of high molecular weight viral [32PJRNA leukemia viruses. These viruses, which include the murine which hybridized to cDNAsff, it was estimated that these se- Abelson (9) and Friend (10-12) leukemia viruses, are replica- quences represent about 50% of the SFFV genome, indicating tion-defective and hence require helper virus to produce in- a genetic complexity of about 3300 nucleotides. cDNAff hy- fectious progeny. Immunological and molecular hybridization bridized extensively (80-95%) to SFFV virion RNA and to cel- analyses of cell clones nonproductively infected with the de- lular RNA from murine and rat cells productively or nonpro- fective Friend focus- ductively infected with SFFV. Only background homology was erythroleukemia-inducing virus, spleen detected between cDNAff and viral RNA from a number of forming virus (SFFV), have indicated that the SFFV genome murine [Friend murine leukemia virus (MuLV), Moloney-MuLV, contains some, but not all, of the sequences found on its helper and Kirsten sarcoma virus] and nonmurine (Rous sarcoma virus, lymphoid leukemia virus (13, 14).
    [Show full text]
  • Envelope Gene of the Friend Spleen Focus-Forming Virus
    Proc. NatL Acad. Sci. USA Vol. 80, pp. 4718-4722, August 1983 Biochemistry Envelope gene of the Friend spleen focus-forming virus: Deletion and insertions in 3' gp70/pl5E-encoding region have resulted in unique features in the primary structure of its protein product (retrovirus/nueleotide sequence/acute erythroleukemia/polycythemia/membrane glycoprotein) LINDA WOLFF*, EDWARD SCOLNICKt, AND SANDRA RUSCETTI* *Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20205; and tMerck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486 Communicated by Peter K. Vogt, May 19, 1983 ABSTRACT A nucleotide sequence was determined for the with endogenous sequences like those of xenotropic and MCF envelope (env) gene of the polycythemia-inducing strain of the acute viruses (11, 12). Our more recent experiments using mono- leukemia-inducing Friend spleen focus-forming virus (SFFV) and clonal antibody and peptide mapping indicate that the domain from this the amino acid sequence of its gene product, gp52, was of gp52 encoded by the endogenously acquired genetic region deduced. All major elements of the gene were found to be related begins at the amino terminus of the protein (13). to genes of other retroviruses that code for functional glycopro- We have determined the nucleotide sequence of the env gene teins. Although the carboxyl terminus of gp52 is encoded by se- of the molecularly cloned (14) polycythemia-inducing form of quences highly related to sequences in its putative parent, eco- SFFV (designated SFFVp) in order to obtain a better under- tropic Friend murine leukemia virus, the majority of the protein the genetic basis for some of the unusual properties (69%), including the amino terminus, is encoded by dualtropic vi- standing of rus-like sequences.
    [Show full text]
  • The Coming of Age of Tumor Virology: Presidential Address1
    [CANCER RESEARCH 37, 1255-1263, May 19771 The Coming of Age of Tumor Virology: Presidential Address1 Charlotte Friend The Center for Experimental Cell Biology, The Mollie B. Roth Laboratory, Mount Sinai School of Medicine, New York, New York mary carcinoma that bears his name. Nevertheless, investi gations along these lines were not completely abandoned. In 1908, the Danish scientists Ellerman and Bang (32) re ported that leukemia in chickens was caused by a filterable agent, but their findings received little attention since leu kemia was not then considered to be a neoplastic disease. Three years later, Rous described a malignant chicken sar coma caused by a virus (96). This paper, which was to become a classic, met with such “downrightdisbelief―(97) that 55 years were to pass before the author, then well over 90, was to be awarded the Nobel Prize for his work. After spending several discouraging years in a fruitless search for similar viruses in transplantable mouse tumors, Rous gave up his study of cancer for almost 20 years. He returned to this first love in 1934, when Richard Shope (105), who had discovered a virus that induced papillomas in rabbits, of fered it to him. He could not resist the study of a virus that caused neoplastic changes in the epithelial cells of a mam malian host. From then to the end of his long and produc tive life, he continued to explore the mechanisms involved in carcinogenesis, but he never again worked on the chicken sarcoma virus that he discovered (RSV).2 Although the climate did not improve much even after Bittner (13) found the virus that causes mammary tumors in mice, a small number of men and women persisted in inves tigating the role that viruses might play in causing a cancer cell to march to a different bugle.
    [Show full text]
  • Animal Models for HIV AIDS: a Comparative Review
    Comparative Medicine Vol 57, No 1 Copyright 2007 February 2007 by the American Association for Laboratory Animal Science Pages 33-43 Animal Models for HIV AIDS: A Comparative Review Debora S Stump and Sue VandeWoude* Human immunodeficiency virus (HIV), the causative agent for acquired immune deficiency syndrome, was described over 25 y ago. Since that time, much progress has been made in characterizing the pathogenesis, etiology, transmission, and disease syndromes resulting from this devastating pathogen. However, despite decades of study by many investigators, basic questions about HIV biology still remain, and an effective prophylactic vaccine has not been developed. This review provides an overview of the viruses related to HIV that have been used in experimental animal models to improve our knowledge of lentiviral disease. Viruses discussed are grouped as causing (1) nonlentiviral immunodeficiency-inducing diseases, (2) naturally occurring pathogenic infections, (3) experimentally induced lentiviral infections, and (4) nonpathogenic lentiviral infections. Each of these model types has provided unique contributions to our understanding of HIV disease; further, a comparative overview of these models both reinforces the unique attributes of each agent and provides a basis for describing elements of lentiviral disease that are similar across mammalian species. Abbreviations: AIDS, acquired immune deficiency syndrome; BIV, bovine immunodeficiency virus; CAEV, caprine arthritis-encephalitis virus; CRPRC, California Regional Primate Research
    [Show full text]
  • Prior Puma Lentivirus Infection Modifies Early Immune
    viruses Article Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats Wendy S. Sprague 1,2,*, Ryan M. Troyer 1,3, Xin Zheng 1, Britta A. Wood 1,4, Martha Macmillian 1, Scott Carver 1,5 ID and Susan VandeWoude 1 1 Department of Molecular Biology, Immunology and Pathology, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins, CO 80523, USA; [email protected] (R.M.T.); [email protected] (X.Z.); [email protected] (B.A.W.); [email protected] (M.M.); [email protected] (S.C.); [email protected] (S.V.) 2 Sprague Medical and Scientific Communications, LLC, Fort Collins, CO 80528, USA 3 Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A5C1, Canada 4 The Pirbright Institute, Pirbright, Surrey GU24 0NF, UK 5 School of Natural Sciences, University of Tasmania, Hobart, Tasmania 7001, Australia * Correspondence: [email protected]; Tel.: +1-970-223-0333 Received: 22 March 2018; Accepted: 12 April 2018; Published: 20 April 2018 Abstract: We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV) and then infected with pathogenic feline immunodeficiency virus (FIV) (co-infection with the host adapted/pathogenic virus) had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4+ T cell preservation, greater interferon gamma (IFN-γ) mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection.
    [Show full text]
  • Co-Infection with the Friend Retrovirus and Mouse Scrapie Does Not Alter Prion Disease Pathogenesis in Susceptible Mice
    Co-Infection with the Friend Retrovirus and Mouse Scrapie Does Not Alter Prion Disease Pathogenesis in Susceptible Mice Pascal Leblanc1,2,3,4, Kim Hasenkrug5, Anne Ward5, Lara Myers5, Ronald J. Messer5, Sandrine Alais1,2,4, Andrew Timmes5, Sue Priola5* 1 Universite´ de Lyon, Lyon, France, 2 Laboratoire de Virologie Humaine, INSERM U758, Lyon, France, 3 Laboratoire de Biologie Mole´culaire de la Cellule, UMR5239, Lyon, France, 4 Ecole Normale Supe´rieure de Lyon, Lyon, France, 5 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America Abstract Prion diseases are fatal, transmissible neurodegenerative diseases of the central nervous system. An abnormally protease- resistant and insoluble form (PrPSc) of the normally soluble protease-sensitive host prion protein (PrPC) is the major component of the infectious prion. During the course of prion disease, PrPSc accumulates primarily in the lymphoreticular and central nervous systems. Recent studies have shown that co-infection of prion-infected fibroblast cells with the Moloney murine leukemia virus (Mo-MuLV) strongly enhanced the release and spread of scrapie infectivity in cell culture, suggesting that retroviral coinfection might significantly influence prion spread and disease incubation times in vivo. We now show that another retrovirus, the murine leukemia virus Friend (F-MuLV), also enhanced the release and spread of scrapie infectivity in cell culture. However, peripheral co-infection of mice with both Friend virus and the mouse scrapie strain 22L did not alter scrapie disease incubation times, the levels of PrPSc in the brain or spleen, or the distribution of pathological lesions in the brain.
    [Show full text]