Virology Education Presentation

Virology What is a virus? It is a small infectious agent that replicates only inside the living cells of another organism. It can infect all types of life forms, from animals and plants to bacteria and archaea. The main purpose of a virus is to deliver its genome into the host cell to allow its expression (transcription and translation) by the host cell. Virus Properties Virus is defined as a nucleoprotein complex which infects cells and uses their metabolic processes to replicate Smallest known infective agents Metabolically inert - no metabolic activity outside host cell; must enter host cell to replicate Most are highly species specific Virus versus Virion Virus is a broad general term for any aspect of the infectious agent and includes: the infectious or inactivated virus particle viral nucleic acid and protein in the infected cell Virion is the physical particle in the extracellular phase which is able to spread to new host cells; complete intact virus particle Characteristics of Infectious Microorganisms Property Bacteria Viruses Fungi Protozoa Size (nm) 100 -10,000 30 - 300 4,000 - 40,000 4,000 - 40,000 Nuclear structure Prokaryotes ---- Eukaryotes Eukaryotes Obligate intracellular No Yes No No Nucleic acids DNA/RNA Haploid DNA or RNA DNA/RNA DNA/RNA Yes No Yes Yes Culture on Artificial media Relative Sizes of Microorganisms Limits of resolution 50,000-V electron microscope 0.003 m Light microscope 0.2 m Unaided human eye 40 m Microscopic protozoa & fungi 4 - 40 m Classes of organisms 0.001 Viruses 0.03 - 0.3 m 0.01 Bacteria 0.1 - 10 m 0.1 1 Size (m) 10 100 History of Virology   Virus discovery came about when the cause of an infectious disease could not be explained by the presence of bacteria  Observation of a virus under electron microscopy and the development of cell tissue culture started the golden era of virology  Eradication of smallpox following a worldwide vaccination program  History of Virology Era Protovirology Years 1796-1885 Descriptiona Before viruses were recognized Auroravirology (named for the 1892-1933 Roman goddess of dawn) Dawn of virology Meridiovirology (from Latin for 1934-1955 midday, sequel to dawn) From the demonstration that bacteriophages are composed of protein and nucleic acid and the crystallization of TMV to the in vitro assembly of infectious TMV from purified RNA and protein Janovirology (named for the Roman god of endings and beginnings) 1956-1975 Spans the interval between classic virology and the beginning of the era dominated by viral sequence information; encompasses the elucidation of essential features of gene structure, expression, and regulation and the development of essential techniques, including cloning and restriction sequence mapping Neovirology 1976-present Begins with the first complete sequencing of viral genomes and atomic resolution structures of intact viruses Era and year Protovirology 1798 1882 1885 Auroravirology 1892 1898 1901 1903 1908 1909 1911 1913 1915 1917 1931 1932 1933 Landmark (virus or scientist) Cowpox lesions used to vaccinate against smallpox (Jenner) Transmission of tobacco mosaic disease with cell-free extracts (Mayer) Development of rabies vaccine (Pasteur, Roux) Description of filterable infectious agent (TMV) (Ivanovsky) Development of concept of virus as contagious element (TMV) (Beijerinck) Discovery of first animal virus (FMDV) (Loeffler, Frosch) Discovery of first human virus (yellow fever virus) (Reed) Discovery of rabies virus (Remlinger, Riffat-Bay) Discovery of first leukemia-causing virus (Ellerman, Bang) Discovery of poliovirus (Landsteiner, Popper) Discovery of first solid tumor virus (RSV) (Rous) Discovery of measles virus (Goldberger, Anderson) Virus cultivation in tissue culture (VV) (Steinhardt, Lambert) Discovery of bacterial viruses (bacteriophages) (Twort, d'Hérelle) Development of the plaque assay and discovery of the particulate nature of viruses (bacteriophage) (d'Hérelle) Propagation of virus in embryonated chicken eggs (Woodruff, Goodpasture) Discovery of first mammalian tumor virus (MMTV) (Little, Bittner) Discovery of human influenza virus (Smith) Discovery of rabbit papillomavirus (Shope) First description of viral mutants (TMV) (Jensen) Era and year Meridiovirology 1934 1935 1938 Landmark (virus or scientist) Discovery that bacteriophages are composed of protein and nucleic acids (Schlesinger) Crystallization of TMV (Stanley) Development of yellow fever vaccine (Theiler) Use of electron microscopy for viruses (TMV) (von Borries, Ruska, Ruska) 1939 Description of one-step growth cycle (bacteriophage) (Ellis, Delbrück) 1941 Discovery of first virus-associated enzymes (influenza virus) (Hirst) 1943 Discovery of genetic origins of mutations (bacteriophage) (Luria, Delbruck) 1945 1946 Development of influenza vaccine (Francis) Discovery of genetic recombination by bacteriophage (Delbruck) Replication of poliovirus in nonneuronal cell cultures (Enders, Weller, Robbins Discovery of eclipse phase of virus infection (bacteriophage) (Doermann) 1951 Discovery of bacteriophage λ (E. Lederberg) Discovery that lysogenic phages produce diphtheria toxin (Freeman) 1952 Plaque assay of animal virus (poliovirus) (Dulbecco) Discovery that viral genome is nucleic acid (Hershey, Chase) Transduction of genetic information by bacteriophage (Zinder, J. Lederberg) 1953 Discovery of host-controlled restriction and modification (Luria, Bertani, Weigle) Development of polio vaccines (Salk, Sabin) 1954 Era and year Janovir ology 1956 Landmark (virus or scientist) Discovery of mRNA in bacteriophage infection (Volkin, Astrachan, Brenner, Jacob, Meselson) Discovery that virus particles are composed of identical subunits (Watson, Crick) Discovery that RNA can carry genetic information (TMV) (Schramm, Fraenkel-Conrat, Williams) 1957 1958 1960 Discovery of interferon (Isaacs, Lindemann) Discovery of respiratory syncytial virus (Chanock) Discovery of bacteriophage λ regulation paradigm (Pardee, Jacob, Monod, Lwoff) Discovery of SV40 (Sweet and Hilleman) Demonstration of the triplet nature of the genetic code (bacteriophage) (Crick) Elucidation of nonsense codons (bacteriophage) (Campbell, Epstein, Bernstein) Studies of virus structure (Klug, Caspar) 1962 1964 1965 1966 1967 Demonstration of the colinearity of gene with polypeptide chain (bacteriophage) (Brenner) Discovery of first human tumor virus (EBV) (Epstein, Barr, Burkitt) Autocatalytic in vitro synthesis of bacteriophage DNA (Spiegelman) Experimental transmission of spongiform encephalopathy to primates (kuru) (Gajdusek, Gibbs, Hadlow) Discovery of hepatitis B virus (Blumberg) Isolation of bacteriophage λ repressor (Ptashne) Era and year Landmark (virus or scientist) Neovirology 1976 First RNA virus genome sequenced (bacteriophage MS2) (Fiers) Demonstration that retroviral oncogenes are derived from cells (J. M. Bishop, Varmus) 1977 First DNA virus genomes sequenced (ΦX174, SV40) (Sanger, Fiers, Weissman) Discovery of RNA splicing (adenovirus) (Roberts, Sharp) Discovery of tumor suppressor p53 (SV40) (Levine, Crawford) Description of first virus crystal structure (TBSV) (Harrison) 1978 Development of the first infectious molecular clone of an RNA virus (Qbeta, Weissmann) 1979 Declaration of smallpox eradication by World Health Organization First in vitro replication of eukaryotic viral DNA (adenovirus, SV40) (Kelly, Hurwitz, Stillman) Development of first in vitro mRNA transcription system (adenovirus) (Roeder) Discovery of first highly active, template-specific, RNA-dependent RNA polymerase from a eukaryotic source (BMV) (Hall) 1980 1981 1982 1983 1984 1986 1988 1989 1990 1991 1995 Discovery of tyrosine kinases (Hunter, Erikson, Eckhart) Discovery of first human retrovirus (HTLV-1) (Gallo) Development of first infectious molecular clones of an animal RNA virus (poliovirus) (Baltimore) Discovery of transcriptional enhancers (Chambon, Khoury, Schaffner) Development of hepatitis B virus vaccine Identification of mammalian transcription factors (MMTV, SV40) (Yamamoto, Tjian) Discovery of insertional activation of cellular oncogenes by retroviruses (Hayward, Astrin) Identification of polyadenylation signal (Shenk) Discovery of the Cre/lox recombination system in phage P1 (Sternberg) Development of antiviral and other drugs (Elion, Hitchings) Definition of prions (Prusiner) High-risk human papillomaviruses identified and linked to cervical cancer (zur Hausen) Discovery of AIDS virus (HIV) (Montagnier, Barre-Sinoussi, Gallo) Discovery of nuclear localization signals (Smith, Butel) Production of first infectious, multicomponent virus from cloned DNA (BMV) (Ahlquist) Development of first recombinant viral vaccine (hepatitis B virus) Generation of transgenic virus-resistant plants (TMV) (Beachy) Discovery of hammerhead ribozymes (TRSV, ASV) (Bruening, Symons) Discovery that DNA virus oncogene products bind cellular tumor suppressor proteins (adenovirus, SV40, HPV) (Harlow, Weinberg, Livingston, Howley) Development of first ribozyme with engineered specificity (Haseloff) Discovery of internal ribosome entry sites (poliovirus) (Wimmer, Sonenberg) Discovery of hepatitis C virus (Houghton) Development of first human gene therapy with a retrovirus vector (Anderson, Blaese) Discovery of viral antiapoptotic proteins (baculovirus) (Miller) Development of HAART treatment for AIDS Viruses  General Structures CLASSIFICATION OF VIRUSES • (1) Nucleic acid type: RNA or DNA; single-stranded or doublestranded; strategy of replication. • (2) Size and morphology, including type of symmetry, number of capsomeres, and presence of membranes. • (3) Presence of specific enzymes, particularly RNA and DNA polymerases, and neuraminidase • (4) Susceptibility to physical and chemical agents, especially ether. • (5) Immunologic properties. • (6) Natural methods of transmission. • (7) Host, tissue, and cell tropisms. • (8) Pathology; inclusion body formation. • (9) Symptomatology. Classification Parameters  Several Parameters Are Used for Classification  Viral classification study is referred to as Taxonomy  73 families exist so far!!  Type of genomic nucleic acid  Size of virion and genome  Capsid structure  Host  Replication mechanism Viruses: Structures   Viral nucleic acid  Viral capsid  Viral envelope  Viral receptor  Viral Nucleic Acid   Polymeric macromolecules essential for all known forms of life  DNA: deoxyribonucleic acid  RNA: ribonucleic acid  Viral capsid   Protein shell of a virus  Protect the viral nucleic acid from detrimental chemical and physical conditions  Characterized by the shape of the capsid  Capsomere – basic unit of a capsid Viral Capsid   Icosahedral  Helical Icosahedral capsid   Constructed from 12 pentamers Prolate Capsid  A prolate capsid is an elongated, or "bacilliform" or "tubular" virus capsid, characterized by a cylinder with two quasiicosahedral caps at its ends, which increases the interior capacity to hold nucleic acid Bacteriophages (viruses that infect bacteria) are a common example of viruses with prolate capsids, including bacteriophage T4. Other examples include ascovirus, badnavirus, Alfalfa mosaic virus (AMV), and Rice tungro bacilliform virus. Helical Capsid  Viral Envelope   Lipidic envelope that surrounds the viral capsid  Originates from the host cells  Added during the replication process or following excision of the viral progeny from the host cells  It fuses with the host membrane allowing the capsid and viral genome to enter and infect the host Viral Receptors   Structures protruding from the viral envelope  Glycoproteins and proteins CLASSIFICATION OF VIRUSES (1) Nucleic acid type: RNA or DNA; single-stranded or doublestranded; strategy of replication. (2) Size and morphology, including type of symmetry, number of capsomeres, and presence of membranes. (3) Presence of specific enzymes, particularly RNA and DNA polymerases, and neuraminidase (4) Susceptibility to physical and chemical agents, especially ether. (5) Immunologic properties. (6) Natural methods of transmission. (7) Host, tissue, and cell tropisms. (8) Pathology; inclusion body formation. (9) Symptomatology. Baltimore Classification System  Class 1: ds DNA Virus  Class 2: ss DNA Virus  Class 3: ds RNA Virus  Class4 and 5: ss RNA  Class 4: ss RNA Virus – Positive Sense  Class 5: ss RNA – Negative Sense  Class 6:Positive –sense – ss RNA  Class 7: ds DNA that replicate through a ss RNA intermediate Class 1: ds DNA Virus   Usually must enter the host nucleus before it is able to replicate  Replication of the viral genome is highly dependent on a cellular state permissive to DNA replication and thus on the cell cycle  Adenoviruses  Herpesviruses  Poxviruses Class 2: ss DNA Virus   They replicate within the nucleus and form a ds DNA intermediate during replication  Parvoviruses Class 3: ds RNA Virus   Do not rely on host polymerases for replication to the extent that viruses with DNA genomes do  Reoviruses  Birnaviruses Class4 and 5: ss RNA   Class 4: ss RNA Virus – Positive Sense  Class 5: ss RNA – Negative Sense Class 4: ss RNA Virus – Positive Sense   Positive sense – can be directly accessed by host ribosomes to immediately form proteins  Picornaviruses  Togaviruses Class 5: ss RNA – Negative Sense   Negative sense – viruses containing non-segmented genomes for which the genes cannot be directly accessed by host ribosomes  They must be transcribed by viral polymerases into readable complementary positive sense  Orthomyxoviruses  Rhabdoviruses Class 6:Positive –sense – ss RNA   Reverse transcriptase and integrase  Retroviruses Class 7: ds DNA that replicate through a ss RNA intermediate   Hepatitis B  form a ccc DNA (covalently closed circle DNA)  Hepadnaviruses DNA Viruses   Poxviruses  Adenoviruses  Herpesviruses  CMV  EBV  Hepadna  Papoviruses RNA Viruses             Myxovirus Paramyxoviruses Rhabdoviruses Reoviruses Picornaviruses Rhinoviruses Togaviruses Flaviviruses Filoviruses Retroviruses Hepatitis C Viruses Virus – Host Cell interaction  Viral Replication   Attachment  Penetration  Uncoating (Disassembly)  Transcription and Translation  Assembly and Release All viruses have to solve three different problems to persist in nature:   Replication inside the cell  Movement from one cell (and host) to another  Evasion of host antiviral defenses What is viral pathogenesis?   Viruses must infect cells to replicate.  Virally infected cells often, but not always, die as a result of the infection – a phenomenon usually described in tissue culture as “cytopathic effect” (CPE).  The “intention” of the host response is to destroy virally infected cells and rid the host of the virus.  Good news: many virally infected cells are destroyed as a result of the immune response.  Bad news: intense antiviral response often does collateral damage to noninfected cells within the organ bearing a viral infection and causes “immunopathology”.   The combinations of virus-induced cell dysfunction and CPE and host response-induced cell destruction are the basic processes involved in viral pathogenesis. Examples of organ-specific effects of viral pathogenesis:   Viral infection of the central nervous system usually results in meningitis, encephalitis or meningoencephalitis.  Viral infections of the respiratory tract are among the most common infections of man.  No matter what the organ system, the basis of viral pathogenesis is the same -- viruses targeting a certain population of human cells in a given organ system , causing a combination of direct cell destruction & an elicited host response that contributes to cell and organ dysfunction (immunopathogenesis). Cultivation of human viruses  Virus Cultivation Systems  1. Biological System 2. Embryonated Eggs 3. Tissue Culture System In-Vivo / In-Vitro? 1. Biological System a) Natural host  b) Experimental animals c) Transgenic animals In - vivo 2. Embryonated Eggs – In - vivo & In - vitro 3. Tissue Culture System – In - Vitro ANIMAL INOCULATIONDISADVANTAGES  Cost Maintenance Interference of immune system Individual variations Difficulty in choosing of animals for particular virus EMBRYONATED EGGS  ADVANTAGES Isolation and cultivation of many avian and few mammalian viruses Ideal receptacle for virus to grow Sterile & wide range of tissues and fluids  Cost- much less Maintenance-easier Less laborious  Readily available   Free from bacteria and many latent viruses.  Free from specific and non specific factors of defense.  Sensitive to viruses which do not produce infection in adult birds. METHODS OF CULTIVATION Routes of inoculation  Yolk sac Allantoic sac Chorioallantoic membrane Amniotic cavity Intravenous VIROLOGY No unauthorized reproduction/sharing/use. Items contain copyright/s. Permission is required from the author/s. GENERALITIES • Smallest infectious agents • Contain only 1 kind of nucleic acid as genome • Acellular Classification • Basis: • Nucleic acid type • Size and morphology • Susceptibility to physical and chemical agents • Enzymes • Immunologic properties • Natural methods of transmission • Host, tissue and cell tropisms • Pathology: inclusion body formation • Symptomatology Classification General Steps in Viral Replication I. • Attachment • Penetration • Uncoating II. • Synthesis of viral components III. • Assembly • Release VIRAL DETECTION TECHNIQUES SPECIMEN COLLECTION: • Obtain specimen during the acute phase • Keep specimen cool and moist • Use of Viral transport media (VTM = buffered isotonic saline + protein + antibiotics) • Container must withstand freezing and thawing • Snap Freezing (-70oC) if processing will be delayed >5 days VIRAL DETECTION TECHNIQUES DETECTION METHODS: 1. Direct Detection 2. Serology 3. Viral Isolation a. use of embryonated eggs b. animal inoculation c. tissue / cell cultures CELL CULTURES 3 BASIC TYPES • Primary cell cultures - short lived • Secondary / Diploid cell lines - up to 50 passages • Continuous / Heteroploid cell lines - immortal cells CELL CULTURES • Cells are propagated in T-shaped plastic flasks • Distributed into new vessels Shell vial Technique - Contains a monolayer on a round glass coverslip on the bottom of the flat-bottom vial - Centrifuged to speed up infection CELL CULTURES DETECTION OF VIRUS INFECTED CELLS: • • • • Development of cytopathic effects (CPEs) Appearance of virus encoded protein Hemadsorption Nucleic acid detection DNA-containing Viruses Family Genus Important Parvoviridae Erythrovirus Parvovirus B19 Papillomaviridae Papillomavirus HPV Polyomaviridae Polyomavirus BK virus, JC virus Adenoviridae Mastadenovirus Adenovirus Hepadnavirus Ortho-hepadnavirus Hepatitis B virus Herpesviridae Simplex virus HSV Varicellovirus Varicella-zoster virus CMV CMV Roseolovirus Human herpesvirus 6 Lymphocryptovirus EBV Orthopox Variola virus, vaccinia virus Parapox Orf virus Poxviridae Parvoviridae • Parvovirus B19 • Tropic for human erythroid cells • Clinical Infections: - erythema infectiosum (5th disease) - transient aplastic anemia - pure red cell aplasia - hydrops fetalis Papovaviridae • Clinical infections (latent and chronic) • Warts (HPV) • Progressive multifocal leukoencephalopathy (JC virus) • Urine of immunosuppressed renal transplant recipients (BK virus) • Can induce tumors Adenoviridae • Clinical Infections: - Respiratory infections - Eye infections (epidemic keratoconjunctivitis) - Gastroenteritis - Mucous membranes / lymphoid tissue Hepatitis Viruses • Produce acute and chronic infections • • • • • • HAV (Hepatitis A Virus) HBV–(Hepatitis B Virus)—the only DNA Hepatitis virus HCV (Hepatitis C Virus) HDV (Hepatitis D Virus) HEV (Hepatitis E Virus) HFV (Hepatitis F Virus) • HGV (Hepatitis G Virus) Herpesviridae • Produce latent infections (ganglial, lymphoblastoid) • Some are cancer causing • CPEs: syncytial cells / multinucleated giant cells - HSV 1 and 2 (alpha) - Varicella-Zoster (alpha) - CMV (beta) - EBV (gamma) - HHV 6 Herpes Simplex Virus • Infections: - Oropharyngeal dse - Keratoconjunctivitis - Genital Herpes - Skin Infections - Encephalitis - Neonatal Herpes - HSV-1: lips, skin, eye - HSV-2: genitals, lips - HSV 6 and 7: T lymphotropic • Virus become latent in nerve cells • Infection is permanent • Detection using Tzanck smear Varicella-Zoster Virus • Chicken Pox - primary infection • Shingles - recurrence of latent infection - lesions are unilateral (corresponds to infected nerve) Diagnosis: - Direct examination reveal syncytial cells Cytomegalovirus • Heterophil negative mononucleosis • IM-like syndrome • Viruses are carried in WBCs • Cultivated in vitro only in human fibroblasts Epstein-Barr Virus • Infects B lymphocytes • Infected cells become immortalized • Only 10% produce infectious progeny • Pathology A. infectious mononucleosis B. Burkitt’s lymphoma C. Nasopharyngeal CA D. Hodgkin’s disease E. Lymphoproliferative Disease in the Immunocompromised • lymphocytic interstitial pneumonitis • hairy oral leukoplakia of the tongue (wart-like lesion) Poxviridae • largest and most complex viruses - multiple membranes - core and lateral bodies • • • • • Variola Vaccinia Orf Molluscum Contagiosum Zoonotic: monkeypox, cowpox RNA-containing Viruses Family Genus Species Picornaviridae Enterovirus Poliovirus, echovirus, coxsackie viruses Hepatovirus Hepatitis A virus Rhinovirus Rhinovirus 1-117 Astroviridae Astrovirus Astroviruses Caliciviridae Calicivirus Hepatitis E virus Reoviridae Coltivirus Colorado Tick fever virus Orthoreovirus Reovirus 1-3 Rotavirus Rotaviruses RNA-containing Viruses Family Genus Species Togaviridae Alphavirus Sindbis virus Rubivirus Rubella virus Flavivirus Yellow fever virus Hepacivirus Hepatitis C virus Coronaviridae Coronavirus SARS virus Orthomyxoviridae Influenzavirus Influenza A, B, C virus Paramyxoviridae Pneumovirus Human RSV Paramyxovirus Human parainfluenza virus 1 and 3 Rubulavirus Mumps virus Morbilivirus Measles virus Flaviviridae RNA-containing Viruses Rhabdoviridae Lyssavirus Rabies virus Filoviridae Filovirus Marburg virus, Ebola virus Bunyaviridae Bunyavirus Bunyamwera virus Nairovirus Crimean-Congo hemorrhagic fever virus Phlebovirus Phlebotomus fever virus Hanta virus Hantaan virus Arenaviridae Arenavirus LCMV, Lassa virus Retroviridae HTLV-retrovirus HTLV I and II Spumavirus Spumavirus Lentivirus HIV 1 and 2 Picornaviridae • Smallest viruses Genera: - Enterovirus (includes echovirus and coxsackie viruses) - Hepatovirus - Parechovirus - Rhinovirus - Apthovirus Poliovirus Clinical Manifestations: • Abortive • Non-Paralytic • Paralytic • Progressive Post Poliomyelitis Muscle Atrophy Coxsackievirus A&B • Wide range of infections • • • • • • • • Aseptic meningitis Herpangina Hand-foot-and-mouth Disease Pleurodynia / epidemic myalgia / Bornholm disease Myocarditis Acute hemorrhagic conjunctivitis Common colds Diarrhea Rhinovirus • Common cold viruses • more than 100 serotypes • Cultured at 33oC Caliciviridae • Norwalk and Norwalk-like viruses • Important cause of gastroenteritis • Associated with food, water, shell-fish • Hepatitis E virus Astroviridae • Gastroenteritis Reoviridae • form pseudoenvelopes • Rotavirus - major cause of diarrheal illness in infants • Coltivirus - causes Colorado tick fever Togaviruses • Rubivirus - Causes German measles/ 3 day measles - Mildest form of exanthem Flaviviridae • Flavivirus • Hepatitis C virus Coronaviridae • Envelope contains petal-shaped peplomers Clinical Infections: - Common colds - Pneumonia (ex. SARS) - Wheezing attacks in asthmatic children Orthomyxoviridae • Influenza viruses • Divided into 3 types (A,B,C) • Frequent antigenic shifts (HA & NA antigens) - seasonal flu vaccine Viral Isolation: - embryonated eggs - kidney cells - infected cells demonstrate hemagglutinins Paramyxoviridae Rubulavirus (mumps) - Parotitis is not an obligatory manifestation - May also infect the pancreas, testes, ovaries, and the CNS Morbillivirus (Rubeola or measles) - Koplick’s spots - Rash – head, chest, trunk, limbs Complications: - secondary bacterial infections - pneumonia - encephalitis - subacute sclerosing panencephalitis Paramyxoviridae • Envelope contains viral hemagglutinin (HN) • Antigenically stable Paramyxovirus (Parainfluenza) A. common colds B. croup (laryngotracheobronchitis) C. pneumonia D. bronchiolitis Pneumovirus (Human Respiratory Syncytial Virus (RSV) - most important pathogen of lower respiratory tract in infants under 1yr of age Rhabdoviridae - Lyssa virus /Rabies virus - bullet-shaped • Acute fulminant encephalitis - IP: 1-2 months (one week - several years) - almost always fatal (2 – 7 days after onset of S/S) - may infect all warm-blooded animals Filoviridae - Filamentous / thread-like - Patients die of hemorrhage and shock Filoviruses: • Marburg - exposure to green monkeys • Ebola - 4 subtypes a. Zaire b. Sudan c. Reston d. Ivory Coast Bunyaviridae • Hanta Virus - via inhalation of aerosols of rodent excreta • La Crosse Virus • California virus: encephalitis Arenaviridae - in EM, host cell ribosomes are visible inside the virus - ribosomes are trapped during assembly • Lassa Fever Retroviridae • Replication involves the enzyme reverse transcriptase HTLV-1 - T-cell lymphomas - tropical spastic paraperesis HTLV-2 - not conclusively associated w/ disease HIV - AIDS Arboviruses • Arthropod-borne viruses • Not a taxonomic group • Most have mosquitoes for vectors Venezuelan Equine Encephalitis Yellow Fever Virus Dengue Japanese Encephalitis West Nile St. Louis encephalitis Arbo- and Robo- viruses Prion Diseases • Transmissible Spongiform Encephalopathy • PrPSc – misfolded protein similar to normal host protein - causes adjacent proteins to convert/misfold • Confined to the nervous system • Always fatal • No host immune response Prion Diseases Animal Diseases: 1. scrapie – sheep 2. transmissible encephalopathy – mink 3. bovine spongiform encephalopathy (BSE) – mad cow disease in cattle Human Diseases: 1. Kuru 2. Creutzfeldt – Jakob Disease • familial forms : A. Gerstmann-Sträussler-Scheinker Syndrome B. Fatal Familial Insomnia mycology