Medical Virology Introduction

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Medical Virology Introduction

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Medical Virology Introduction

  1. 1. Medical Virology Introduction to Basics Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 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 2
  3. 3. Virus infections are Universal …….
  4. 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 4
  5. 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 5
  6. 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 6
  7. 7. Viruses are UltramicroscopicKoneman et al. Color Atlas and Textbook of Microbiology 5th Ed. 1997 Dr.T.V.Rao MD 7
  8. 8. The size of viruses Dr.T.V.Rao MD 8
  9. 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 9
  10. 10. Virion• The complete infectious unit of virus particle• Structurally mature, extracellular virus particles. Dr.T.V.Rao MD 10
  11. 11. Virion envelope Capsid Dr.T.V.Rao MD Viral core 11
  12. 12. Virion Structure Lipid Envelope Nucleic AcidProteinCapsidVirionAssociated SpikePolymerase Projections Dr.T.V.Rao MD 12
  13. 13. Distinguishing characteristics of viruses• Obligate intracellular parasites• Extreme genetic simplicity• Contain DNA or RNA• Replication involves disassemblyand reassembly• Replicate by "one-step growth” Dr.T.V.Rao MD 13
  14. 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 14
  15. 15. Virus particle = virion White, DO and Fenner, FJ. Medical Virology, 4th Ed. 1994 Dr.T.V.Rao MD 15
  16. 16. 5 BASIC TYPES OF VIRAL STRUCTURE icosahedral nucleocapsid nucleocapsid lipid bilayer ICOSAHEDRAL ENVELOPED ICOSAHEDRAL helical nucleocapsid COMPLEX nucleocapsid lipid bilayer glycoprotein spikes = peplomers HELICAL ENVELOPED HELICAL Dr.T.V.Rao MDAdapted from Schaechter et al., Mechanisms of Microbial Disease 16
  17. 17. Dr.T.V.Rao MD 18
  18. 18. Icosahedral• Adeno-associated Virus (AAV) • Herpes Simplex Virus 1 (HHV1) Adenovirus Herpes Simplex Virus 2 (HHV2) B19 Human Immunodeficiency Virus (HIV) Coxsackievirus - A Human T-lymphotrophic Virus (HTLV) Coxsackievirus - B Norwalk Virus Papilloma Virus (HPV) Cytomegalovirus (CMV) Polio virus Eastern Equine Encephalitis Rhinovirus Virus (EEEV) Rubella Virus Echovirus Saint Louis Encephalitis Virus Epstein-Barr Virus (EBV) Varicella-Zoster Virus (HHV3) Western Equine Encephalitis Virus Hepatitis A Virus (HAV) (WEEV) Hepatitis B Virus (HBV) Yellow Fever Virus Hepatitis C Virus (HCV) Hepatitis Delta Virus (HDV) Hepatitis E Virus (HEV) Dr.T.V.Rao MD 19
  19. 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
  20. 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 viruseswhere "ds" represents "double strand" and "ss" denotes "singlestrand". Dr.T.V.Rao MD 21
  21. 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
  22. 22. From Principles of Virology Flint et al ASM PressDr.T.V.Rao MD 23
  23. 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
  24. 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
  25. 25. Viral Structure - Overview Nucleic acid Nucleocapsid Capsid Envelope protein Viral envelope** Membrane protein Spike proteinFig 1. Schematic overview of the structure of animal viruses** does not exist in all viruses Dr.T.V.Rao MD 26
  26. 26. Icosahedral capsidsa) Crystallographic structure of a b) The axes of symmetrysimple icosahedral virus. Dr.T.V.Rao MD 27
  27. 27. Cubic or icosahedral symmetry Dr.T.V.Rao MD 28
  28. 28. ICOSAHEDRAL SYMMETRY Dr.T.V.Rao MD 29
  29. 29. ICOSAHEDRAL SYMMETRY Dr.T.V.Rao MD 30
  30. 30. ICOSAHEDRAL SYMMETRY Dr.T.V.Rao MD 31
  31. 31. ICOSAHEDRAL SYMMETRY Dr.T.V.Rao MD 32
  32. 32. Adenovirus Dr.T.V.Rao MD 33
  33. 33. Adenovirus Dr.T.V.Rao MD 34
  34. 34. Helical symmetry Dr.T.V.Rao MD 35
  35. 35. Helical• California Encephalitis Virus Coronavirus Hantavirus Influenza Virus (Flu Virus) Measles Virus ( Rubeola) Mumps Virus Para influenza Virus Rabies Virus Respiratory Syncytial Virus(RSV) Dr.T.V.Rao MD 36
  36. 36. • Helical symmetry How to assemble Dr.T.V.Rao MD 37
  37. 37. Helical symmetryIn 1955, Fraenkel,Conrat, and Williamsdemonstrated thattobacco mosaic virus(TMV) spontaneouslyformed when mixturesof purified coatprotein and itsgenomic RNA were TMV, a filamentous virusincubated together. Dr.T.V.Rao MD 38
  38. 38. Enveloped helical virus Enveloped icosahedral virus Dr.T.V.Rao MD 39
  39. 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. 40. Naked viruses( Non Enveloped )• Adeno-associated Virus (AAV) Adenovirus B19 Coxsackievirus - A Coxsackievirus - B Echovirus Hepatitis A Virus (HAV) Hepatitis E Virus (HEV) Norwalk Virus
  41. 41. COMPLEX SYMMETRY surface view cross sectionWhite, DO and Fenner, FJ.Medical Virology, 4th Ed. 1994 POXVIRUS FAMILY Dr.T.V.Rao MD 42
  42. 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
  43. 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
  44. 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
  45. 45. DNA RNA double- double-stranded single-stranded single-stranded strandedline line circular circular linear linear (circular)* ar arsingl sing multip singl sing multip singl multipl (+)sense (-)sense e le le e le le e e sing multip sing multip le le le le Dr.T.V.Rao MD 46
  46. 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
  47. 47. DNA VIRUSES DOUBLE STRANDED SINGLE STRANDED COMPLEX NON-ENVELOPED ENVELOPED ENVELOPED NON-ENVELOPED PARVOVIRIDAE POXVIRIDAE HERPESVIRIDAEHEPADNAVIRIDAE CIRCULAR LINEAR PAPILLOMAVIRIDAE ADENOVIRIDAE All families shown are POLYOMAVIRIDAE icosahedral except for (formerly grouped together as the poxviruses PAPOVAVIRIDAE) Dr.T.V.Rao MD Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991 48
  48. 48. DNA viruses From Principles of Virology Flint et al ASM Press Dr.T.V.Rao MD 49
  49. 49. RNA VIRUSES SINGLE STRANDED SINGLE STRANDED DOUBLE STRANDED positive sense negative sense ENVELOPED NONENVELOPED ENVELOPED NONENVELOPED ICOSAHEDRAL HELICAL ICOSAHEDRAL HELICAL ICOSAHEDRAL FLAVIVIRIDAE CORONAVIRIDAE PICORNAVIRIDAE ORTHOMYXOVIRIDAE REOVIRIDAE TOGAVIRIDAE CALICIVIRIDAE PARAMYXOVIRIDAERETROVIRIDAE ASTROVIRIDAE RHABDOVIRIDAE FILOVIRIDAE BUNYAVIRIDAE ARENAVIRIDAE Dr.T.V.Rao MD Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991 50
  50. 50. RNA viruses From Principles of Virology Flint et al ASM Press Dr.T.V.Rao MD 51
  51. 51. BASIC STEPS IN VIRAL LIFE CYCLE• ADSORPTION• PENETRATION• UNCOATING AND ECLIPSE• SYNTHESIS OF VIRAL NUCLEIC ACID AND PROTEIN• ASSEMBLY (maturation)• RELEASE Dr.T.V.Rao MD 52
  52. 52. RECEPTOR VIRUSICAM-1 polioCD4 HIVacetylcholine rabiesEGF vacciniaCR2/CD21 Epstein- BarrHVEM herpesSialic acid Influenza, reo, corona
  53. 53. Virus Replication 1 Virus attachment and entry1 2 Uncoating of virion 3 Migration of genome nucleic 5 acid to nucleus 4 Transcription 4 Genome replication2 5 6 Translation of virus 3 mRNAs 7 Virion assembly 7 Release of new 8 virus particles 6 8 Dr.T.V.Rao MD 54
  54. 54. ADSORPTION• TEMPERATURE INDEPENDENT• REQUIRES VIRAL ATTACHMENT PROTEIN• CELLULAR RECEPTORS Dr.T.V.Rao MD 55
  55. 55. PENETRATION - ENVELOPED VIRUSES•FUSION WITH PLASMA MEMBRANE•ENTRY VIA ENDOSOMES Dr.T.V.Rao MD 56
  56. 56. PENETRATIONherpesviruses, paramyxoviruses, HIV Dr.T.V.Rao MD 57
  57. 57. PENETRATION - ENVELOPED VIRUSES•FUSION WITH PLASMA MEMBRANE•ENTRY VIA ENDOSOMES, FUSION WITHACIDIC ENDOSOME MEMBRANE Dr.T.V.Rao MD 58
  58. 58. Dr.T.V.Rao MD 59
  59. 59. Dr.T.V.Rao MD 60
  60. 60. VIRUS UPTAKE VIA ENDOSOMES• CALLED –VIROPEXIS / ENDOCYTOSIS / PINOCYTOSIS Dr.T.V.Rao MD 61
  61. 61. PENETRATION NON-ENVELOPED VIRUSESentry directly acrossplasma membrane: Dr.T.V.Rao MD 62
  62. 62. Dr.T.V.Rao MD 63
  63. 63. Replicative cycle• As obligate intracellular parasites, Virus must enter and replicate in living cells in order to “reproduce” themselves. This “growth cycle” involves specific attachment of virus, penetration and uncoating, nucleic acid transcription, protein synthesis, maturation and assembly of the virions and their subsequent release from the cell by budding or lysis Dr.T.V.Rao MD 64
  64. 64. Dr.T.V.Rao MD 65
  65. 65. Dr.T.V.Rao MD 66
  66. 66. UNCOATING• NEED TO MAKE GENOME AVAILABLE• ONCE UNCOATING OCCURS, ENTER ECLIPSE PHASE• ECLIPSE PHASE LASTS UNTIL FIRST NEW VIRUS PARTICLE FORMED Dr.T.V.Rao MD 67
  67. 67. SYNTHESIS OF VIRAL NUCLEIC ACID AND PROTEIN• MANY STRATEGIES• NUCLEIC ACID MAY BE MADE IN NUCLEUS OR CYTOPLASM• PROTEIN SYNTHESIS IS ALWAYS IN THE CYTOPLASM Dr.T.V.Rao MD 68
  68. 68. ASSEMBLY AND MATURATION• NUCLEUS• CYTOPLASM• AT MEMBRANE Dr.T.V.Rao MD 69
  69. 69. RELEASE• LYSIS• BUDDING THROUGH PLASMA MEMBRANE• NOT EVERY RELEASED VIRION IS INFECTIOUS Dr.T.V.Rao MD 70
  70. 70. Transmission of Viruses • Respiratory transmission – Influenza A virus • Faecal-oral transmission – Enterovirus • Blood-borne transmission – Hepatitis B virus • Sexual Transmission – HIV • Animal or insect vectors – Rabies virus Dr.T.V.Rao MD 71
  71. 71. Viruses enter the body of the hostin a variety of ways, for example... Dr.T.V.Rao MD 72
  72. 72. The commonest forms of transmission are via... INHALED DROPLETS in sneezing of coughingfor example the COMMON COLD or INFLUENZA VIRUSES. Dr.T.V.Rao MD 73
  73. 73. or by ... drinking water oreating raw food, for example,HEPATITIS A and POLIOVIRUS. Dr.T.V.Rao MD 74
  74. 74. The commonest forms of transmission are also via...sexual intercourse for example HIV and HEPATITIS B and... Dr.T.V.Rao MD 75
  75. 75. also... vertical transmission -from mother to baby for example HIV, HEPATITIS B and RUBELLA... Dr.T.V.Rao MD 76
  76. 76. also... bites of vector arthropods such asmosquitoes for example YELLOW FEVER, RIFT VALLEY FEVER and DENGUE. Dr.T.V.Rao MD 77
  77. 77. Most viral infections... do not lead to such seriouscomplications and the host... Dr.T.V.Rao MD 78
  78. 78. get well after a period of sicknessto be immune for the rest of their lives. Examples are MEASLES INFECTION, RUBELLADr.T.V.Rao MD or German measles, 79 MUMPS and many others...
  79. 79. A bacteriophage• A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid. The genetic material can be ssRNA, dsRNA, ssDNA, or dsDNA (ss- or ds- prefix denotes single- strand or double-strand) along with either circular or linear arrangement. Dr.T.V.Rao MD 80
  80. 80. Structure of Bacteriophage Dr.T.V.Rao MD 81
  81. 81. Classification of Bacteriophages• The dsDNA tailed phages, or Caudovirales, account for 95% of all the phages reported in the scientific literature, and possibly make up the majority of phages on the planet. However, other phages occur abundantly in the biosphere, with different virions, genomes and lifestyles. Phages are classified by the International Committee on Taxonomy of Viruses (ICTV) according to morphology and nucleic acid. Dr.T.V.Rao MD 82
  82. 82. Sub-viral agents• Satellites – Contain nucleic acid – Depend on co-infection with a helper virus – May be encapsidated (satellite virus) – Mostly in plants, can be human e.g. hepatitis delta virus – If nucleic acid only = virusoid• Viroids – Unencapsidated, small circular ssRNA molecules that replicate autonomously – Only in plants, e.g. potato spindle tuber viroid – Depend on host cell polII for replication, no protein or mRNA• Prions – No nucleic acid – Infectious protein e.g. BSE Dr.T.V.Rao MD 83
  83. 83. Viroids & Prions• Viroids – ss RNA genome and the smallest known pathogens. – Affects plants• Prions – Infectious particles that are entirely protein. – No nucleic acid – Highly heat resistant – Animal disease that affects nervous tissue – Affects nervous tissue and results in • Bovine spongiform encepahltits (BSE) “mad cow disease”, • scrapie in sheep • kuru & Creutzfeld-Jakob Disease (CJD) in humans Dr.T.V.Rao MD 84
  84. 84. Viroids• Viroids are small (200-400nt), circular RNA molecules with a rod- like secondary structure which possess no capsid or envelope which are associated with certain plant diseases. Their replication strategy like that of viruses - they are obligate intracellular parasites.
  85. 85. Dependovirus /Virusoids• Viroids are small (200-400nt), circular RNA molecules with a rod-like secondary structure which possess no capsid or envelope which are associated with certain plant diseases. Their replication strategy like that of viruses - they are obligate intracellular parasites.
  86. 86. (Prions)• Prions are rather ill-defined infectious agents believed to consist of a single type of protein molecule with no nucleic acid component. Confusion arises from the fact that the prion protein & the gene which encodes it are also found in normal uninfected cells. These agents are associated with diseases such as Creutzfeldt-Jakob disease in humans, scrapie in sheep & bovine spongiform encephalopathy (BSE) in cattle.
  87. 87. • Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 88

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