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Medical Virology Introduction

Medical Virology Introduction

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Medical Virology Introduction

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  1. Medical VirologyIntroduction to Basics Dr.T.V.Rao MD Dr.T.V.Rao MD

  2. History Virology • Smallpox was endemic in China by 1000BC. In response, the practice of variolation was developed. Recognizing that survivors of smallpox outbreaks were protected from subsequent infection, variolation involved inhalation of the dried crusts from smallpox lesions like snuff, or in later modifications, inoculation of the pus from a lesion into a scratch on the forearm of a child. Dr.T.V.Rao MD

  3. Virus infections are Universal …….

  4. Introduction to Virology • A virus is an obligate intracellular parasite containing genetic material surrounded by protein • Virus particles can only be observed by an electron microscope Dr.T.V.Rao MD

  5. Introduction to Virology • Recognizing the shape, size, and structure of different viruses is critical to the study of disease • Viruses have an inner core of nucleic acid surrounded by protein coat known as an envelope • Most viruses range in sizes from 20 – 250 nanometers Dr.T.V.Rao MD

  6. Viral Properties • Viruses are inert (nucleoprotein ) filterable Agents • Viruses are obligate intracellular parasites • Viruses cannot make energy or proteins independent of a host cell • Viral genome are RNA or DNA but not both. • Viruses have a naked capsid or envelope with attached proteins • Viruses do not have the genetic capability to multiply by division. • Viruses are non-living entities Dr.T.V.Rao MD

  7. Viruses are Ultramicroscopic Koneman et al. Color Atlas and Textbook of Microbiology 5th Ed. 1997 Dr.T.V.Rao MD

  8. The size of viruses Dr.T.V.Rao MD

  9. VIRAL STRUCTURE – SOME TERMINOLOGY • virus particle = virion • protein which coats the genome = capsid • capsid usually symmetrical • capsid + genome = nucleocapsid • may have an envelope Dr.T.V.Rao MD

  10. Virion • The complete infectious unit of virus particle • Structurally mature, extracellular virus particles. Dr.T.V.Rao MD

  11. Virion envelope Capsid Viral core Dr.T.V.Rao MD

  12. Lipid Envelope Nucleic Acid Protein Capsid Virion Associated Polymerase Spike Projections Virion Structure Dr.T.V.Rao MD

  13. Distinguishing characteristics of viruses • Obligate intracellular parasites • Extreme genetic simplicity • Contain DNA or RNA • Replication involves disassembly and reassembly • Replicate by "one-step growth” Dr.T.V.Rao MD

  14. How are viruses named? • Based on: - the disease they cause poliovirus, rabies virus - the type of disease murine leukemia virus - geographic locations Sendai virus, Coxsackie virus - their discovers Epstein-Barr virus - how they were originally thought to be contracted dengue virus (“evil spirit”), influenza virus (the “influence” of bad air) - combinations of the above Rous Sarcoma virus Dr.T.V.Rao MD

  15. Virus particle = virion White, DO and Fenner, FJ. Medical Virology, 4th Ed. 1994 Dr.T.V.Rao MD

  16. 5 BASIC TYPES OF VIRAL STRUCTURE nucleocapsid icosahedralnucleocapsid lipid bilayer ICOSAHEDRAL ENVELOPED ICOSAHEDRAL helicalnucleocapsid COMPLEX nucleocapsid lipid bilayer glycoprotein spikes = peplomers HELICAL ENVELOPED HELICAL Dr.T.V.Rao MD Adaptedfrom Schaechter et al., Mechanisms of Microbial Disease

  17. Dr.T.V.Rao MD

  18. Adeno-associated Virus (AAV)AdenovirusB19Coxsackievirus - ACoxsackievirus - BCytomegalovirus (CMV)Eastern Equine Encephalitis Virus (EEEV)EchovirusEpstein-Barr Virus (EBV)Hepatitis A Virus (HAV)Hepatitis B Virus (HBV)Hepatitis C Virus (HCV)Hepatitis Delta Virus (HDV)Hepatitis E Virus (HEV) Herpes Simplex Virus 1 (HHV1)Herpes Simplex Virus 2 (HHV2)Human Immunodeficiency Virus (HIV)Human T-lymphotrophic Virus (HTLV)Norwalk VirusPapilloma Virus (HPV)Polio virusRhinovirusRubella VirusSaint Louis Encephalitis VirusVaricella-Zoster Virus (HHV3)Western Equine Encephalitis Virus (WEEV)Yellow Fever Virus Icosahedral Dr.T.V.Rao MD

  19. Viral Structure • Varies in size, shape and symmetry • VIP for classification • 3 types of capsid symmetry: • Cubic (icosahedral) • Has 20 faces, each an equilateral triangle. Eg. adenovirus • Helical • Protein binds around DNA/RNA in a helical fashion eg. Coronavirus • Complex • Is neither cubic nor helical eg. poxvirus Dr.T.V.Rao MD

  20. The Baltimore classification system Based on genetic contents and replication strategies of viruses. According to the Baltimore classification, viruses are divided into the following seven classes: 1. dsDNA viruses 2. ssDNA viruses 3. dsRNA viruses 4. (+) sense ssRNA viruses (codes directly for protein) 5. (-) sense ssRNA viruses 6. RNA reverse transcribing viruses 7. DNA reverse transcribing viruses where "ds" represents "double strand" and "ss" denotes "single strand". Dr.T.V.Rao MD

  21. Virus Classification I- the Baltimore classification • All viruses must produce mRNA, or (+) sense RNA • A complementary strand of nucleic acid is (–) sense • The Baltimore classification has + RNA as its central point • Its principles are fundamental to an understanding of virus classification and genome replication, but it is rarely used as a classification system in its own right Dr.T.V.Rao MD

  22. From Principles of Virology Flint et al ASM Press Dr.T.V.Rao MD

  23. Virus classification II -the Classical system • This is a based on three principles - • 1) that we are classifying the virus itself, not the host • 2) the nucleic acid genome • 3) the shared physical properties of the infectious agent (e.g capsid symmetry, dimensions, lipid envelope) Dr.T.V.Rao MD

  24. Virus classification III -the genomic system • More recently a precise ordering of viruses within and between families is possible based on DNA/RNA sequence • By the year 2000 there were over 4000 viruses of plants, animals and bacteria - in 71 families, 9 subfamilies and 164 genera Dr.T.V.Rao MD

  25. Nucleic acid Capsid Envelope protein Membrane protein Viral envelope** Nucleocapsid Viral Structure - Overview Spike protein Fig 1. Schematic overview of the structure of animal viruses ** does not exist in all viruses Dr.T.V.Rao MD

  26. Icosahedral capsids a) Crystallographic structure of a simple icosahedral virus. b) The axes of symmetry Dr.T.V.Rao MD

  27. Cubic or icosahedral symmetry Dr.T.V.Rao MD

  28. 5-FOLD 3-FOLD 2-FOLD ICOSAHEDRAL SYMMETRY Dr.T.V.Rao MD

  29. ICOSAHEDRAL SYMMETRY Dr.T.V.Rao MD

  30. CAPSOMER ICOSAHEDRAL SYMMETRY = PENTON (pentamer) Dr.T.V.Rao MD

  31. CAPSOMER CAPSOMER = HEXON ICOSAHEDRAL SYMMETRY = PENTON Dr.T.V.Rao MD

  32. Adenovirus Dr.T.V.Rao MD

  33. 12 PENTONS 240 HEXONS Adenovirus Dr.T.V.Rao MD

  34. Helical symmetry Dr.T.V.Rao MD

  35. Helical • California Encephalitis VirusCoronavirusHantavirusInfluenza Virus (Flu Virus)Measles Virus ( Rubeola)Mumps VirusPara influenza VirusRabies VirusRespiratory Syncytial Virus(RSV) Dr.T.V.Rao MD

  36. Helical symmetry How to assemble Dr.T.V.Rao MD

  37. Helical symmetry In 1955, Fraenkel, Conrat, and Williams demonstrated that tobacco mosaic virus (TMV) spontaneously formed when mixtures of purified coat protein and its genomic RNA were incubated together. TMV, a filamentous virus Dr.T.V.Rao MD

  38. Enveloped helical virus Enveloped icosahedral virus Dr.T.V.Rao MD

  39. Properties of naked viruses • Stable in hostile environment • Not damaged by drying, acid, detergent, and heat • Released by lysis of host cells • Can sustain in dry environment • Can infect the GI tract and survive the acid and bile • Can spread easily via hands, dust, fomites, etc • Can stay dry and still retain infectivity • Neutralizing mucosal and systemic antibodies are needed to control the establishment of infection

  40. Naked viruses( Non Enveloped ) • Adeno-associated Virus (AAV)AdenovirusB19Coxsackievirus - ACoxsackievirus - BEchovirusHepatitis A Virus (HAV)Hepatitis E Virus (HEV)Norwalk Virus

  41. COMPLEX SYMMETRY surface view cross section POXVIRUS FAMILY White, DO and Fenner, FJ. Medical Virology, 4th Ed. 1994 Dr.T.V.Rao MD

  42. ENVELOPE • OBTAINED BY BUDDING THROUGH A CELLULAR MEMBRANE (except poxviruses) • POSSIBILITY OF EXITING CELL WITHOUT KILLING IT • CONTAINS AT LEAST ONE VIRALLY CODED PROTEIN • ATTACHMENT PROTEIN • LOSS OF ENVELOPE RESULTS IN LOSS OF INFECTIVITY Dr.T.V.Rao MD

  43. CLASSIFICATION NUCLEIC ACID • RNA or DNA • segmented or non-segmented • linear or circular • single-stranded or double-stranded • if single-stranded RNA • is genome mRNA (+) sense or complementary to mRNA (-) sense Dr.T.V.Rao MD

  44. Genome • The genome of a virus can be either DNA or RNA • DNA-double stranded (ds): linear or circular Single stranded (ss) : linear or circular • RNA- ss:segmented or non-segmented ss:polarity+(sense) or polarity –(non-sense) ds: linear (only reovirus family) Dr.T.V.Rao MD

  45. DNA RNA double-stranded single-stranded double-stranded single-stranded linear circular linear circular linear linear (circular)* single single multiple single single multiple single multiple (+)sense (-)sense single multiple single multiple Dr.T.V.Rao MD

  46. Viral genome strategies • dsDNA (herpes, papova, adeno, pox) • •ssDNA (parvo) • •dsRNA (reo, rota) • •ssRNA (+) (picorna, toga, flavi, corona) • •ssRNA (-) (rhabdo, paramyxo, orthomyxo, • bunya, filo) • •ssRNA (+/-) (arena, bunya) • •ssRNA (+RTase) (retro, lenti) Dr.T.V.Rao MD

  47. DNA VIRUSES DOUBLE STRANDED SINGLE STRANDED COMPLEX NON-ENVELOPED ENVELOPED PARVOVIRIDAE POXVIRIDAE ENVELOPED NON-ENVELOPED HERPESVIRIDAE HEPADNAVIRIDAE CIRCULAR LINEAR All families shown are icosahedral except for poxviruses PAPILLOMAVIRIDAE POLYOMAVIRIDAE (formerly grouped together as the PAPOVAVIRIDAE) ADENOVIRIDAE Dr.T.V.Rao MD Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991

  48. DNA viruses From Principles of Virology Flint et al ASM Press Dr.T.V.Rao MD

  49. RNA VIRUSES SINGLE STRANDED SINGLE STRANDED DOUBLE STRANDED positive sense negative sense ENVELOPED NONENVELOPED ENVELOPED NONENVELOPED HELICAL ICOSAHEDRAL HELICAL ICOSAHEDRAL ICOSAHEDRAL ORTHOMYXOVIRIDAE FLAVIVIRIDAE CORONAVIRIDAE PICORNAVIRIDAE REOVIRIDAE PARAMYXOVIRIDAE CALICIVIRIDAE ASTROVIRIDAE TOGAVIRIDAE RHABDOVIRIDAE RETROVIRIDAE FILOVIRIDAE BUNYAVIRIDAE ARENAVIRIDAE Dr.T.V.Rao MD Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991

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