General Virology- RNA viruses

virology - RNA viruses

1. General Virology and Overview of Viral Infections

2. GENERAL PROPERTIES OF VIRUSES 2

3. GENERAL PROPERTIES OF VIRUSES 3 Smallest unicellular organisms that are obligate intracellular. Viruses are the most primitive microorganisms infecting man.

4. Viruses differ from bacteria as: 4 Obligate intracellular Possess either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), but never both Smaller than bacteria, can be passed through the bacterial filters Cannot be grown on artificial cell free media (grow in animals, embryonated eggs or tissue culture)

5. Viruses differ from bacteria as (Cont..): 5 Multiply by a complex method (not by binary fission). Do not have a proper cellular organisation. Do not have cell wall or cell membrane or cellular organelles including ribosomes Lack the enzymes necessary for protein and nucleic acid synthesis. ­ Not susceptible to antibacterial antibiotics

6. MORPHOLOGY OF VIRUS 6

7. MORPHOLOGY OF VIRUS 7 The entire virus particle called as virion , comprises of a nucleic acid (DNA or RNA) surrounded by a protein coat called as capsid , together known as the nucleocapsid . Some viruses also have an outer envelope.

8. Nucleic Acid 8 Viruses have only one type of nucleic acid, either DNA or RNA. They are classified as DNA viruses and RNA viruses. Nucleic acid - single or double stranded, circular or linear, segmented or unsegmented.

9. Nucleic Acid (Cont..) 9 Most DNA viruses possess dsDNA, except parvoviruses, which have ssDNA. RNA viruses possess ssRNA , except: Reoviruses (e.g. rotaviurs )–possess dsRNA Retrovirsues –possess two copies of ssRNA

10. Capsid 10 Composed of a number of repeated protein subunits (polypeptides) called capsomeres . Functions: Protects the nucleic acid core from the external environment In non-enveloped viruses - initiates the first step of viral replication. Antigenic and specific for each virus.

11. Symmetry 11 Based on arrangement of capsomeres : Type of symmetry Explanation Examples Icosahedral (cubical) symmetry Capsomeres are arranged as if they lay on the faces of an icosahedron 20 triangular facets and 12 corners or vertices Rigid structure. All DNA viruses (except poxviruses) Most of the RNA viruses have icosahedral symmetry

12. Symmetry (Cont..) 12 Based on arrangement of capsomeres : Type of symmetry Explanation Examples Helical symmetry Capsomeres are coiled surrounding the nucleic acid in the form of a helix or spiral. Flexible structure. RNA viruses such as- myxoviruses , rhabdoviruses , filoviruses, bunyaviruses , etc.

13. Symmetry (Cont..) 13 Based on arrangement of capsomeres : Type of symmetry Explanation Examples Complex symmetry Do not have either of the above symmetry. Poxviruses

14. Envelope 14 Envelope surrounding the nucleocapsid . Lipoprotein in nature. Lipid part is derived from host cell membrane Protein part is virus coded, made up of subunits called peplomers . Peplomers - project as spikes on the surface of the envelope.

15. Envelope (Cont..) 15 Most Viruses are Enveloped Except: Non-enveloped DNA viruses - parvovirus, adenovirus and papovavirus Non-enveloped RNA viruses - picornavirus, reovirus , calicivirus , hepatitis A virus and hepatitis E virus.

16. Size of the Viruses 16 Size vary from 20-300nm in size. Smallest virus - parvovirus(20 nm) Largest - poxvirus (300nm). Because of the small size, viruses can pass through bacterial filters and they cannot be visualized under light microscope.

17. Size of the Viruses (Cont..) 17

18. Shapes of the Viruses 18 Most of the animal viruses are roughly spherical with some exceptions: Rabies virus: Bullet shaped Ebola virus: Filamentous Poxvirus: Brick shaped Adenovirus: Space vehicle shaped Rotavirus: wheel shaped Tobacco mosaic virus: Rod shaped

19. NOMENCLATURE AND CLASSIFICATION 19

20. NOMENCLATURE AND CLASSIFICATION 20 Family DNA type Envelope Symmetry Size (nm) Representative Viruses DNA viruses DNA Herpesviridae ds,linear Yes Icosahedron 150-200 Herpes simplex virus - 1 Herpes simplex virus- 2 Varicella-zoster virus Epstein-Barr virus Cytomegalovirus Human herpes virus 6,7 & 8 Hepadnaviridae ds, circular, incomplete Yes Icosahedron 40–48 Hepatitis B virus Parvoviridae ss, linear Absent Icosahedron 18–26 Parvovirus B19

21. NOMENCLATURE AND CLASSIFICATION (Cont..) 21 Family DNA type Envelope Symmetry Size (nm) Representative Viruses DNA viruses DNA Papovaviridae ds, circular Absent Icosahedron 45-55 Human papillomaviruses JC virus and BK virus Poxviridae ds, linear Yes Complex 230 x 400 Variola (smallpox) Molluscum contagiosum virus Adenoviridae ds, linear Absent Icosahedron 70–90 Human adenoviruses

22. NOMENCLATURE AND CLASSIFICATION (Cont..) 22 Family DNA type Envelope Symmetry Size (nm) Representative Viruses RNA viruses RNA Picornaviridae ss , + ve sense Absent Icosahedral 28–30 Poliovirus Coxsackievirus Echovirus Enterovirus Rhinovirus Hepatitis A virus Caliciviridae ss, +ve sense Absent Icosahedral 27-40 Norwalk agent Hepatitis E virus Togaviridae ss, +ve sense Yes Icosahedral 50-70 Rubella virus Eastern equine encephalitis virus Western equine encephalitis virus

23. NOMENCLATURE AND CLASSIFICATION (Cont..) 23 Family DNA type Envelope Symmetry Size (nm) Representative Viruses RNA viruses RNA Flaviviridae ss, +ve sense Yes Icosahedral (?) 40-60 Yellow fever virus Dengue virus St. Louis encephalitis virus West Nile virus Hepatitis C virus Coronaviridae ss, +ve sense Yes Helical 120-160 Coronaviruses Rhabdoviridae ss, -ve sense Yes Helical 75x180 Rabies virus Vesicular stomatitis virus Filoviridae ss, -ve sense Yes Helical 80 x 1000 Marburg virus Ebola virus

24. NOMENCLATURE AND CLASSIFICATION (Cont..) 24 Family DNA type Envelope Symmetry Size (nm) Representative Viruses RNA viruses RNA Paramyxoviridae ss, -ve sense Yes Helical 150–300 Parainfluenza virus Mumps virus Measles virus Respiratory syncytial virus Newcastle disease virus Metapneumovirus Orthomyxoviridae ss , - ve sense, 8 segments Yes Helical 80–120 Influenza viruses- A, B, and C Bunyaviridae ss , - ve sense, 3 circular segments Yes Helical 80–120 Hantavirus California encephalitis virus Sandfly fever virus

25. NOMENCLATURE AND CLASSIFICATION (Cont..) 25 Family DNA type Envelope Symmetry Size (nm) Representative Viruses RNA viruses RNA Arenaviridae ss , - ve sense, RNA,2 circular segments Yes Helical (?) 50-300 Lymphocytic choriomeningitis virus Lassa fever virus South American hemorrhagic fever virus Reoviridae ds, 10–12 segments Absent Icosahedral 60-80 Rotavirus Reovirus Colorado tick fever virus Retroviridae 2 identical copies of + ve sense ss RNA Yes Icosahedral (spherical) 80-110 HTLV (Human T Lymphotropic virus) HIV (Human immunodeficiency virus)

26. VIRAL REPLICATION 26

27. VIRAL REPLICATION 27 Viruses undergo a complex way of cell division. Replication of viruses passes through six sequential steps: Attachment →Penetration → Uncoating → Biosynthesis→ Maturation → Release

28. 28

29. PATHOGENESIS OF VIRAL INFECTIONS 29

30. PATHOGENESIS OF VIRAL INFECTIONS 30 Transmission (entry into the body) Primary site replication Spread to secondary site Manifestations of the disease

31. Transmission and spread of viruses 31 Mode of transmission Produce Local infection at the portal of entry Spread to distant sites from the portal of entry Respiratory route (probably the most common route) Produce Respiratory infection- Influenza virus Parainfluenzavirus Respiratory syncytial virus Rhinovirus Adenovirus Coronavirus such as SARS-COV2 Herpes simplex virus Measles virus Mumps virus Rubella virus Varicella-zoster virus Cytomegalovirus Parvovirus Small pox virus Oral route Produce gastroenteritis Rotavirus Adenovirus-40,41 Calicivirus Astrovirus Poliovirus Coxsackie virus Hepatitis Virus – A & E Cytomegalovirus Epstein-Barr virus (EBV)

32. Transmission and spread of viruses (Cont..) 32 Mode of transmission Produce Local infection at the portal of entry Spread to distant sites from the portal of entry Cutaneous route Produce skin lesions Herpes simplex virus Human papilloma virus Molluscumcontagiosum virus Herpes simplex virus     Vector bite - Arboviruses such as- Dengue virus ( Aedes ) Chikungunya virus( Aedes ) Japanese encephalitis virus ( Culex ) Yellow fever and Zika virus( Aedes ) Kyasanur Forest disease virus (Tick) Animal bite - Rabies virus

33. Transmission and spread of viruses (Cont..) 33 Mode of transmission Produce Local infection at the portal of entry Spread to distant sites from the portal of entry Sexual route Produce genital lesions- Herpes simplex virus Human papilloma virus Hepatitis B, C& rarely D HIV   Blood transfusion - Hepatitis B, C & rarely D HIV Parvovirus Injection - Hepatitis B, C & rarely D HIV

34. Transmission and spread of viruses (Cont..) 34 Mode of transmission Produce Local infection at the portal of entry Spread to distant sites from the portal of entry Transplacental route Produce congenital manifestations in fetus Rubella virus Cytomegalovirus (CMV) Herpes simplex virus Varicella-zoster virus Parvovirus Transmitted through placenta to fetus, without congenital manifestations Measles virus Mumps virus Hepatitis B virus Hepatitis C virus Hepatitis D virus HIV Conjunctival route Adenovirus Enterovirus70 Coxsackie virus A-24 Herpes simplex virus  

35. Virus Shedding 35 Stages Explanation Examples Portal of entry For those viruses that produce local infection. Influenza virus is shed in respiratory secretions Blood Viruses that spread through vector bite or blood transfusion or needle pricks Arboviruses, h epatitis B Near the target tissue /organ Skin, salivary gland and kidney Varicella zoster , mumps, cytomegalovirus No shedding Humans are the dead end for certain viruses infecting CNS, such as Rabies.

36. Manifestations of Viral Infections (Cont..) 36 Clinical Manifestations (Cont..): Respiratory viruses such as influenza and coronaviruses produce upper and lower respiratory tract infections Gastroenteritis may be produced by viruses such as rotavirus and norovirus Hemorrhagic fever may be a manifestation of viruses such as dengue, Ebola virus etc Neurotropic viruses can produce meningitis (enteroviruses) or encephalitis (rabies, Japanese encephalitis)

37. Morphological Changes in the Host Cells 37 Certain viruses induce characteristic changes in the host cells (e.g. inclusion body ), which can be detected by histopathological staining.

38. Inclusion body 38 Aggregates of virions or viral proteins & other products of viral replication that confer altered staining property to the host cell. Characteristic of specific viral infections. They have distinct size, shape, location and staining properties by which they can be demonstrated in virus infected cells under the light microscope.

39. Inclusion body (Cont..) 39 Intracytoplasmic inclusion bodies Negri bodies – seen in Rabies virus Paschen body- seen in Variola virus Guarnieri bodies - seen in Vaccinia virus ­Bollinger bodies - seen in Fowl pox virus Molluscum bodies - seen in Molluscum contagiosum virus Perinuclear cytoplasmic body- seen in Reovirus

40. Inclusion body (Cont..) 40 Intranuclear inclusion bodies A) Cowdry type A inclusions Torres body- seen in Yellow fever Lipschultz body - seen in Herpes simplex B) Cowdry type B inclusions - seen in Poliovirus Adenovirus Intracytoplasmic & intranuclear inclusion bodies Owl’s eye appearance- seen in Cytomegalovirus Measles

41. LABORATORY DIAGNOSIS OF VIRAL DISEASES 41

42. LABORATORY DIAGNOSIS OF VIRAL DISEASES (Cont..) 42 Direct Demonstration of Virus Electron microscopy Immunoelectron microscopy Fluorescent microscopy Light microscopy Detection of Viral Antigens By various formats such as ELISA, direct IF, ICT, flow through assays.

43. LABORATORY DIAGNOSIS OF VIRAL DISEASES (Cont..) 43 Detection of Specific Antibodies Conventional techniques such as HAI, neutralization test and CFT Newer diagnostic formats such as ELISA, ICT, flow through assays. Molecular Methods to Detect Viral Genes Nucleic acid probe—for detection of DNA or RNA by hybridization PCR—for DNA detection by amplification Reverse transcriptase-PCR—for RNA detection Real time PCR—for DNA quantification Real time RT-PCR—for RNA quantification.

44. LABORATORY DIAGNOSIS OF VIRAL DISEASES (Cont..) 44 Isolation of Virus by Animal inoculation Embryonated egg inoculation Tissue cultures: Organ culture, explant culture, cell line culture (primary, secondary and continuous cell lines).

45. TREATMENT OF VIRAL DISEASES 45

46. TREATMENT OF VIRAL DISEASES 46 Anti-Viral drugs Mechanism of action Active against Anti-herpesvirus drugs Acyclovir , Valacyclovir , Penciclovir Inhibit Viral DNA polymerase HSV1>HSV2>VZV&EBV Famciclovir Inhibit Viral DNA polymerase HSV,VZV,HBV Ganciclovir Inhibit Viral DNA polymerase CMV,EBV, HSV, VZV Cidofovir Inhibit Viral DNA polymerase HSV,CMV Foscarnet Inhibit Viral DNA polymerase HSV& CMV Fomivirsen Inhibit mRNA of CMV CMV(including resistant strains) Docosanol (topical) Inhibit the fusion of the human host cell with envelope of herpes virus HSV (recurrent herpes labialis ) Trifluridine (topical) Inhibits viral DNA polymerase Herpes keratitis (eye drops)

47. TREATMENT OF VIRAL DISEASES (Cont..) 47 Anti-Viral drugs Mechanism of action Active against Anti- Influenza virus drugs Oseltamivir, Zanamivir Neuraminidase Inhibitor H1N1flu Avian flu Seasonal flu Amantadine, Rimantadine Matrix protein inhibitor Seasonal flu

48. TREATMENT OF VIRAL DISEASES (Cont..) 48 Anti-Viral drugs Mechanism of action Active against Anti-Hepatitis drugs Telbivudine , tenofovir , lamivudine, adefovir , entecavir Nucleoside analogues Primarily for Hepatitis B Interferon alfa Indirectly inhibits viral protein synthesis For hepatitis B and C infection Grazoprevir Paritaprevir , Simeprevir NS3/4A inhibitors (proteases) For hepatitis C infection Dasabuvir , Sofosbuvir NS5B inhibitors (polymerases) For hepatitis C infection Daclatasvir , Ledipasvir , Velpatasvir NS5A inhibitors For hepatitis C infection Ribavirin Nucleoside inhibitor For For hepatitis C infection

49. IMMUNOPROPHYLAXIS FOR VIRAL DISEASES 49

50. Viral Vaccines (Active Immunization) 50 Since viral antigens are potent immunogens, viral vaccines confer prolonged and effective immunity. Vaccines for viral infections may be available either in live, killed or in subunit forms.

51. Killed Viral Vaccines 51 Preparation: By inactivating viruses with heat, phenol, formalin or beta propiolactone . Ultraviolet irradiation is not recommended because of the risk of multiplicity reactivation. E.g., Rabies vaccine . Advantages- They are more stable and are safely when given in immunodeficiency or in pregnancy. Disadvantages- Killed vaccines are associated with more adverse side effects due to reactogenicity , which can be reduced to some extent by purification of viruses.

52. Subunit Vaccines 52 Only a particular antigen of the virus is incorporated in the subunit vaccine. Preparation - DNA recombinant technology. The gene coding for the desired antigen is integrated into bacteria or yeast chromosome. Replication of the bacteria or yeast yields a large quantity of desired antigens, e.g. Hepatitis B vaccine Unlike killed vaccines, there is no local side effects associated with subunit vaccines

53. Live Vaccines 53 Preparation- Most of the live vaccines are prepared by attenuation by serial passages. (Exception is small pox vaccinewhere the naturally occurring vaccinia viruses were used for vaccination). Advantage- Live vaccines provide a stronger and long lasting immunity, mimickingimmunity produced after natural infection. They are administered as a single dose (except OPV). Disadvantages - Live vaccines are risky in immunodeficiency or pregnancy. They are less stable than killed vaccines

54. Passive Immunization (Immunoglobulin) 54 Passive immunization is indicated when an individual is immunodeficient or when an early protection is needed (i.e. for post-exposure prophylaxis). However, as there is no Passive immunization has no role in prevention of subsequent infections. Human immunoglobulins are available for many viral infections such as mumps, measles, hepatitis B, rabies and varicella-zoster.

55. Combined Immunization 55 Simultaneous administration of vaccine and immunoglobulin in post exposure prophylaxis is extremely useful. It is recommended for- Hepatitis B (neonates born to HBsAg positive mothers or for unvaccinated people following exposure ) Rabies (for exposures to severe class III bites)

56. MYXOVIRUSES 56 Group of viruses that bind to mucin receptors on the surface of RBCs. They are divided into two families: Orthomyxoviridae - They possess segmented RNA; e.g. influenza virus Paramyxoviridae - They possess non-segmented RNA; e.g. parainfluenza virus, mumps, measles, nipah , and respiratory syncytial virus.

57. Influenza Virus 57 Major cause of morbidity and mortality. Responsible for several epidemics and pandemics of respiratory diseases in the last two centuries, caused by various serotypes; of which the latest pandemic was caused by H1N1 serotype in 2009.

58. Influenza Virus (Cont..) 58 Types: Based on hemagglutinin (HA) and neuraminidase (NA) antigen, Influenza comprises of four types (A to D). Influenza type A is further divided into various subtypes.

59. Influenza Virus (Cont..) 59 Seasonal flu: Currently circulating strains causing seasonal flu are influenza A/H1N1, A/H3N2 and influenza B. Clinical manifestations: Majority of individuals develop mild flu-like symptoms such as chills, headache, and dry cough, followed by high-grade fever, myalgia and anorexia.

60. Influenza Virus (Cont..) 60 Laboratory diagnosis - detection of viral RNA in nasopharyngeal swabs by real-time reverse transcriptase PCR. Treatment: Neuraminidase inhibitors (e.g. oseltamivir) or matrix protein M2 inhibitor (e.g. amantadine). Vaccine: Both live attenuated and injectable vaccines are available for influenza.

61. Parainfluenza Viruses 61 Major cause of respiratory tract disease in young children; producing various infections such as mild common cold syndrome, croup ( laryngotracheobronchitis ), pneumonia or bronchiolitis.

62. Mumps Virus 62 Most common cause of parotid gland enlargement in children. In severe cases, it can also cause orchitis and aseptic meningitis. Transmitted through the respiratory route via droplets, saliva, and fomites. Live attenuated vaccine is available for the prevention of mumps.

63. Measles Virus 63 Acute, highly contagious childhood disease, characterized by fever and respiratory symptoms, followed by, appearance of Koplik’s spots on buccal mucosa and maculopapular rash. Rarely, post measles complications may occur such as giant cell pneumonitis, subacute sclerosing panencephalitis (SSPE). Prevented by administration of a live attenuated vaccine, given at nine months of birth.

64. Nipah and Hendra Viruses 64 Cause an emerging viral infection (encephalitis). Transmitted to humans after direct contact with infected bats, pigs, or persons. Latest outbreak of Nipah encephalitis occurred in Kerala, India in 2018.

65. Respiratory Syncytial Virus 65 Major respiratory pathogen of young children and is the most common cause of bronchiolitis in infants.

66. RUBELLA VIRUS 66

67. RUBELLA VIRUS 67 Rubella - important agent of childhood exanthema. In addition, it is highly teratogenic and can cause congenital malformations affecting organs such as eye, ear and heart in fetus (congenital rubella syndrome). Live attenuated vaccine - available for rubella; recommended for children and young women.

68. PICORNAVIRUSES 68

69. PICORNAVIRUSES 69 Include two major groups of human pathogens: enteroviruses and rhinoviruses. Enteroviruses are transmitted by feco -oral route - include polioviruses, coxsackieviruses and others. Rhinoviruses are transmitted by respiratory route and cause common cold.

70. Poliovirus 70 Causative agent of polio (also known as poliomyelitis). Pathogenesis - transmitted by feco -oral route and then spreads to CNS/spinal cord by hematogenous route. Clinical manifestation - Majority of infections are asymptomatic; rarely progresses to aseptic meningitis and paralytic poliomyelitis.

71. Poliovirus (Cont..) 71 Vaccine - Killed injectable and live oral polio vaccines are available. Eradication - Poliomyelitis is now at the verge of eradication. This is attributed to the extensive immunization program being conducted globally.

72. Coxsackievirus 72 Produce a variety of clinical illnesses in humans, such as Aseptic meningitis, Hand-foot-and mouth disease, Conjunctivitis, Myocarditis, Pericarditis and Pancreatitis.

73. ARBOVIRUSES 73

74. ARBOVIRUSES 74 Arboviruses (arthropod-borne viruses) are diverse group of RNA viruses that are transmitted by blood sucking arthropods (insect vectors) from one vertebrate host to another.

75. ARBOVIRUSES (Cont..) 75 India: The following are the important arboviruses prevalent in India. Dengue virus Chikungunya virus Kyasunar forest disease (KFD) virus Japanese B encephalitis

76. RABIES VIRUS 76

77. RABIES VIRUS 77 Causes a rapidly progressive, acute infectious disease of the central nervous system in humans and animals. Transmission - transmitted from another infected animal bite (most common being dog). Clinical manifestation - From the site of bite, it spreads to CNS via neuronal route - produces an acute neurologic phase, which may be either encephalitic or paralytic type.

78. RABIES VIRUS (Cont..) 78 Laboratory diagnosis : Detection of rabies viral antigen from hair follicles at nape of the neck by direct IF test. Antibody detection Viral RNA detection by RT PCR. Postmortem diagnosis - detection of characteristic inclusion bodies ( Negri bodies) in histopathological staining of brain tissue.

79. RABIES VIRUS (Cont..) 79 Management : Post-exposure prophylaxis can be provided by local wound care and administration of antirabies immunoglobulin and vaccine.

80. HUMAN IMMUNODEFICIENCY VIRUS (HIV) 80

81. HUMAN IMMUNODEFICIENCY VIRUS (HIV) 81 Etiologic agent of acquired immunodeficiency syndrome (AIDS); the biggest threat to mankind in last three decades. Transmission: Sexual route (most commonly) vertical (mother to fetus), parenteral (blood transfusion) percutaneous (needle prick injury).

82. HUMAN IMMUNODEFICIENCY VIRUS (HIV) (Cont..) 82 Pathogenesis: Following transmission, HIV infects CD4 T cells and where the unique viral enzyme ‘reverse transcriptase’ converts viral RNA to DNA, which then integrates with host DNA and undergoes latency.

83. HUMAN IMMUNODEFICIENCY VIRUS (HIV) (Cont..) 83 Clinical manifestations: Typical course of HIV infection includes following stages - Acute retroviral syndrome, followed by asymptomatic stage (clinical latency), then progresses into persistent generalized lymphadenopathy, and symptomatic HIV infection. Finally, the patients move towards the advanced end stage called AIDS.

84. HUMAN IMMUNODEFICIENCY VIRUS (HIV) (Cont..) 84 Laboratory diagnosis: Detection of antibodies (by rapid tests or ELISA or western blot), p24 antigen (by ELISA), or viral RNA (by RT-PCR). In India, the strategy recommended by national AIDS control organization (NACO) is used for HIV diagnosis.

85. HUMAN IMMUNODEFICIENCY VIRUS (HIV) (Cont..) 85 Treatment : Antiretroviral Therapy (ART) is advocated for treatment of HIV infected patients. The NACO recommended first-line ART regimen in adults includes combination of tenofovir , lamivudine and efavirenz (TLE regimen).

86. CORONAVIRUSES 86

87. CORONAVIRUSES 87 Widespread and produce mild upper respiratory tract infection. Two exceptions are SARS- CoV (severe acute respiratory syndrome coronavirus), and MERS- CoV (Middle East respiratory syndrome coronavirus); which are geographically restricted - transmitted from man to man and have produced outbreaks of severe respiratory disease with higher mortality.

88. COVID-19 88 SARS-CoV-2 has emerged in 2019-2020 in China and then rapidly spread to other part of the World causing a catastrophic global pandemic known as COVID-19 (coronavirus disease-2019). Epidemiology: Till June 2020, 1 crore cases have been reported worldwide with 5 Lakh deaths. Although >200 countries were effected, the worst affected are USA, Brazil, Russia and India.

89. COVID-19 (Cont..) 89 Diagnosis: real time RT-PCR in throat swab or nasopharyngeal swab Treatment: No effective drug or vaccine has been developed yet, although intense research is ongoing. Control measures : control measures such as social distancing, lockdown, hand hygiene and use of mask.

90. HEPATITIS VIRUSES 90

91. HEPATITIS VIRUSES 91 Heterogeneous group of viruses that are taxonomically diverse (belong to different families) but all are hepatotropic ; and produce similar clinical illness such as fever, nausea, vomiting, and jaundice. There are five important hepatitis viruses (A to E). All are RNA viruses except HBV which is a DNA virus. They can be divided into two groups based on the route of transmission.

92. HEPATITIS VIRUSES (Cont..) 92 Hepatitis A and E viruses: Transmitted by feco -oral route. The clinical course has an abrupt onset. Disease is self-limiting with good prognosis. They do not have carrier stage, or chronicity or oncogenic potential. .

93. HEPATITIS VIRUSES (Cont..) 93 Hepatitis B, C and D viruses: Transmitted by percutaneous, sexual or vertical routes. The clinical course has an insidious onset and variable prognosis. The disease may progress to carrier stage, chronic hepatitis, cirrhosis or hepatocellular carcinoma.

94. HEPATITIS VIRUSES (Cont..) 94 Laboratory diagnosis of viral hepatitis includes detection of various viral markers such as: Detection of viral antigens (e.g. HBsAg for HBV) or Detection of antibodies [anti-HAV, anti- HBc and anti-HBs (for HBV), anti-HCV and anti-HEV] or Detection of viral nucleic acid (by PCR).

95. HEPATITIS VIRUSES (Cont..) 95 Treatment : HAV and HEV infections are self-limiting, do not require specific treatment. Antiviral drugs are available for HBV and HCV infections; for example, Tenofovir and telbivudine - for HBV Interferon, ribavirin for - HCV Vaccine: Vaccines - available for HAV and HBV.

96. MISCELLANEOUS RNA VIRUSES 96

97. Rodent-borne Viruses 97 Transmitted from rodents to man by contact with infected body fluids or excretions. Major rodent-borne viruses include: Hantaviruses - cause two categories of manifestations - hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Arenaviruses - cause various diseases such as South American hemorrhagic fever.

98. Filoviruses 98 Long filamentous viruses; example include Ebola virus and Marburg virus. They cause hemorrhagic fever, associated with very high mortality. Transmitted by close contact with blood or other body fluids or secretions of infected animals or man.

99. Slow Viruses and Prions 99 Group of neurodegenerative conditions affecting both humans and animals. Characterized by: long incubation period, predilection for CNS and a strong genetic predisposition.

100. Slow Viruses and Prions (Cont..) 100 Conventional slow viruses: Examples include - subacute sclerosing pan encephalitis, progressive multifocal leukoencephalopathy. Unconventional transmissible slow viruses - termed as ‘ prion disease ’, characterized by spongiform encephalopathies due to deposition of abnormal prion proteins in neural tissues.

101. Questions: 101 Q1. Which of the following virus is enveloped : Poliovirus Adenovirus Herpesvirus Parvovirus B19

102. Questions: 102 Q2. All of the following viruses are transmitted by respiratory route, except : Influenza virus Rotavirus RSV Rhinovirus

103. Questions: 103 Q3. Which of the following vaccine is a killed vaccine : Mumps vaccine Measles vaccine Rubella vaccine IPV

104. Questions: 104 Q4. The largest virus in size is : Herpes simplex virus Hepatitis B virus Poxvirus Adenovirus

105. Questions: 105 Q5. Which of the following DNA virus is single stranded : Parvovirus Hepatitis B virus Poxvirus Adenovirus

106. Questions: 106 Q6. Human fibroblast cell line is used for cultivation of : Measles CMV Poliovirus Adenovirus