Chapter 18. Eucaryotic Viruses and other acellular infectious agents

Transcription

1 Chapter 18 Eucaryotic Viruses and other acellular infectious agents

2 Taxonomy of Eucaryotic Viruses most of the ~5,000 known viruses infect eucaryotic organisms Virus classification by the ICTV Genome structure Replication strategy Morphology Genetic relatedness Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2

3 Viruses that Infect Vertebrates Figure 18.1 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 3

4 Reproduction of Animal Viruses adsorption penetration and uncoating replication of virus nucleic acids synthesis and assembly of virions virion release Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 4

5 Table 18.1 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 5

6 Penetration and Uncoating fusion of envelope with host cell membrane Fig 18.4 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 6

7 Endocytosis enveloped virus Figure 18.4 (b) Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7

8 Endocytosis naked virus Figure 18.4 (c) Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8

9 Replication and transcription in DNA Viruses - Herpes simplex virus I uses host RNA polymerase for synthesis of viral mrna uses virusencoded DNA polymerase for genome replication Figure 18.6 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 9

10 Poxviruses large, morphologically complex doublestranded DNA (dsdna) viruses virion carries DNA-dependent RNA polymerase that synthesizes early mrna encodes DNA polymerase and other enzymes needed for DNA replication Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 10

11 Hepadnaviruses- HBV circular, partial dsdna genome transcribed by host RNAP generates several mrna molecules one for pregenome RNA others encode polymerase with reverse transcriptase activity pregenome converted to dsdna by virus polymerase (+RNA -DNA 2S DNA) 11

12 Replication and Transcription in RNA Viruses very diverse reproductive strategies four general modes of replication and transcription 12

13 Pico-RNA Para- and ortho- Myxo- affinity to mucin Respiratory-enteric-orphan Figure 18.8 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 13

14 Assembly of Virus Capsids late genes direct capsid protein synthesis which spontaneously selfassemble to form the capsid during icosahedral virus assembly empty procapsids form first, nucleic acid are then inserted assembly of envelope viruses in most cases, similar to assembly of naked viruses Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 14 site of morphogenesis varies

15 Figure 18.2 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 15

16 Virion Release naked viruses usually by lysis of host cell envelope viruses formation of envelope and release usually occur concurrently (budding) virus-encoded proteins incorporated into host membrane nucleocapsid buds outward and is surrounded by modified host membrane Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 16

17 Release of influenza virus by budding Figure Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17

18 HIV release by budding Figure (a) Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 18

19 Mechanisms of host cell damage and cell death inhibition of host DNA, RNA, and protein synthesis lysosome damage causes release of hydrolytic enzymes alteration of plasma membrane lead to attack of host by immune system lead to cell fusion, forming syncytium Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 19

20 Other mechanisms toxicity from high concentrations of viral proteins formation of inclusion bodies can disrupt cell structure the Negri bodies in rabies infected neurons chromosomal disruptions transform host cell into malignancy Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 20

21 Types of viral infections (Fig. 18.3) acute infections rapid onset and relatively short duration persistent infections- last many years Chronic infection, e.g, HBV infection Latent infection, e.g., Herpes virus infection - 21

22 Types of persistent infections chronic virus infection virus almost always detectable clinical symptoms mild or absent for long periods latent virus infection virus stops reproducing and remains dormant for some time during latency, symptoms, antivirusantibodies, and viruses are not detectable Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22

23 Possible causes of persistent infections integration of viral genome into host genome decrease in antigenicity of virus mutation to less virulent and slower reproducing form defective interfering (DI) particle deletion mutant that cannot reproduce and slows reproduction of normal virus Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 23

24 Slow virus diseases Symptoms take years to emerge subacute sclerosing panencephalitis caused by measles virus HIV infections Prion Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 24

25 Prion A small proteinaceous infectious particle Passes through the filter (100 nm) and still transmits disease resistant to a wide range of chemical and physical treatment inactivated at 121 o C 1 h

26 Prion-caused degenerative diseases Scrapie bovine spongiform encephalopathy (BSE) or mad cow disease Creutzfeldt-Jakob disease (CJD) and variant CJD (vcjd) Kuru Scrapie- cause intense itching - The prototype of prion - A natural progressive brain disease Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 26

27 Kuru- shivering or trembling 1950, occurred in the Fore tribe of New Guinea highlands Related to the cannibalistic practices Blurred speech, silly smiles, and dementia lose the ability to walk, talk, and see

28 The 1 st Nobel Prize for prion study 1976, Carleton Gajdusek (1923~) retired as chief of the laboratory of CNS at NIH Demonstrated Kuru s etiology an infectious invisible slow (~ 30 y incubation period) virus as that of Scrapie? Never saw any inflammation!

29 Creutzfeldt-Jakob disease (CJD) The human form of mad cow disease BSE (Bovine Spongiform encephalopathy) Identified by Creutzfeldt and Jakob (1920) A progressive fatal neurodegenerative disease Usually aged between 50~75 Characterized by seizures, massive incoordination, dementia

30 Transmission of CJD Injection with contaminated growth hormone Transplantation of contaminated corneas Contact with contaminated medical devices brain electrodes- Iatrogenic Ingestion of infected tissue 1996 in UK, causes an unusual incidence of CJD in young people (<45 yr)- new variant of CJD/ vcjd Blood transfusion and spread of vcjd (Emerg Infect Dis 2007)

31 Inheritable CJD- prnp A Gerstmann-Straussier-Scheinker syndrome A Kuru like familial disease Inherited forms emerge earlier (~ 45 yr) familial CJD, GSS, fatal familial insomnia (FFI)- 10~15% specific mutation of the gene on chromosome 20- prnp

32 Current Model of Disease Production by Prions PrP C (prion protein): normal form PrP Sc : abnormal form entry of PrP Sc into animal brain causes PrP C to change its conformation to abnormal form the newly produced PrP Sc convert more to the abnormal form interactions between PrP Sc and PrP C crosslinking of PrP C neuron loss Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 32

33 The 2 nd Nobel prize- Prion pathogenesis PrP sc binds to the normal PrP c on the cell surface, causing it to be processed into PrP sc - a replicating protein, to be released from the cell, and to be aggregated as amyloid-like plaques in the brain Vacuolated neurons (loss of function and lack of an immune response) 1997, Stanley Prusiner (1942~) for showing that PrP sc is sufficient to cause disease Director of institute of neurodegenerative disease UCSF

34 Viruses and Cancer tumor growth or lump of tissue neoplasia abnormal new cell growth and reproduction due to loss of regulation anaplasia reversion to a more primitive or less differentiated state metastasis Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 34 spread of cancerous cells throughout body

35 Carcinogenesis complex, multistep process often involves oncogenes cancer-causing genes many involved in regulation of cell growth and differentiation some viruses contribute to carcinogenesis Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 35

36 Viruses implicated in human cancers Epstein-Barr virus Hepatitis B virus Hepatitis C virus Burkitt s lymphoma nasopharyngeal carcinoma liver cancer hepatoma liver cancer Human herpesvirus 8 HIV human papillomavirus HTLV-1 and HTLV-2 Kaposi s sarcoma cervical cancer Copyright The McGraw-Hill Companies, Inc. Permission required leukemia for reproduction or display 36

37 Possible mechanisms by which viruses cause cancer carry oncogene into cell and insert it into host genome altered cell regulation due to changes in kinase activity or production of regulatory proteins insertion of promoter or enhancer next to cellular oncogene Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display 37

38 Chapter 37 Human Diseases Caused by Viruses 38

39 Airborne Diseases when human is source, airborne viruses are propelled from respiratory tract by coughing, sneezing, or vocalizing 39

40 Chickenpox (Varicella) caused by varicella-zoster virus results from initial infection Attenuated vaccine 40 Figure 37.1

41 Shingles (herpes zoster) postherpetic neuralgia reactivated form of chickenpox Figure 37.2

42 Flu or common cold clinical manifestations chills, fever, headache, malaise, and general muscular aches and pains recovery usually within 3 to 7 days often leads to secondary infections by bacteria rhinitis, tonsillitis, laryngitis, bronchitis, and pneumonia treatment, prevention, and control symptomatic/supportive therapy inactivated virus vaccine 42

43 43 Influenza (Flu) by influenza virus Orthomyxovirus (segmented virus) Classified into A, B, and C groups 16 HA and 9 NA Influenza Pandemics 1918, HswN1 (Spanish flu) 50~ 100 million moratlity 1947, H1N1 1957, H2N2 (Asian flu) 1968, H3N2 (Hong Kong flu) 1977, H1N1 (Russian flu) Avian flu- H5N1(1997~)

44 Generation of a reassortant virus - broad host range and segmented genome Reassortant virus

45 Avian flu virus H9N2 (1998/1999) China and Hong Kong H7N7 (2003) Netherlands H5N1 in human (1997~2003~) Hong Kong, China, and worldwide. since 2003, > 300 infected and > 150 died Emerging Infectious Diseases (2007) October

46 SARS (Severe Acute Respiratory Syndrome) An emerging disease cause by coronavirus Flu-like syndrome Vaccine target? - Virus of the year ( ) Where is the SARS virus?? Box a mutation in spike protein 46

47 Classification of coronaviruses 3 groups coronaviruses: groups 1 and 2: mammalian viruses group 3 contains only avian viruses Classified into distinct species by host range, antigenic relationships, and genomic organization 47

48 Phylogenetic analyses of SARS-CoV sequences 48

49 Measles (Rubeola) caused by measles virus subacute sclerosing panencephalitis rare progressive degeneration of central nervous system caused by measles virus treatment, prevention, and control symptomatic/supportive therapy attenuated measles vaccine MMR vaccine (measles, mumps, rubella) Figure

50 Mumps caused by mumps virus pleomorphic, enveloped virus helical nucleocapsid negative strand RNA Figure

51 Rubella (German Measles) caused by rubella virus ssrna virus spread by respiratory droplets congenital rubella syndrome infection of pregnant women in first trimester fetal death, premature delivery, and/or congenital defects live attenuated vaccine: MMR- measles, mumps, rubella 51

52 Human immunodeficiency virus (HIV) 1983, HIV was correlated with AIDS (acquired immunodeficiency syndrome) A retrovirus (an RNA virus) believed to have evolved in Africa from a monkey virus 2006 CDC estimation: ~ 1 million HIV infections in USA Converging HIV and MDR-TB (multidrug resistance tuberculosis) Outbreaks Worsen

53 Figure 37.7 HIV

54 Transmission Acquired and passed from person to person when infected blood, semen or vaginal secretions come in contact with uninfected person s broken skin or mucous membranes Groups most at risk in descending order homosexuals intravenous drug users heterosexuals with drug users and prostitutes children of infected mothers and breast-fed infants transfusion patients and transplant recipients

55 HIV pathogenesis Once inside host, HIV gp120 envelope protein binds to host CD4+ glycoprotein plasma membrane receptor on CD4 + cells Figure 37.8

56 Acquired Immune Deficiency Syndrome (AIDS) caused by human immunodeficiency virus (HIV) occurs world wide, causing the great pandemic of the second half of the twentieth century retrovirus theories on origin of disease HIV-1 evolved from chimp virus SIVcpz use of human blood products in chimps infected animals with HIV-1 precursor that evolved into SIVcpz

57 Course of Disease some patients rapidly develop clinical AIDS; die within 2-3 years some patients remain relatively healthy for at least 10 years post infection in majority of patients HIV infection progresses to AIDS in 8-10 years

58 CDC classification for HIV-related stages AIDS- fourth and last stage immune system no longer able to defend against virus definition of AIDS all HIV-infected individuals who has fewer than 200 CD4 + T cells/microliter of blood or a CD4 + cell percentage of lymphocytes of less than 14

59 AIDS-related cancers Kaposi s sarcoma caused by human herpesvirus 8 carcinoma of mouth and rectum B-cell lymphomas

60 AIDS-related central nervous system disease headaches, fever, subtle cognitive changes, abnormal reflexes, and ataxia dementia and severe sensory and motor changes observed in advanced cases autoimmune neuropathies, cerebrovascular disease, and brain tumors are common

61 61 Viral Hepatitis hepatitis inflammation of liver caused by different viruses Epstein-Barr virus (EBV) cytomegalovirus (CMV) cause mild, self-resolving disease no permanent hepatic damage signs and symptoms include fatigue, nausea, and malaise hepatotropic viruses (HAV, HBV, HCV, HDV, HEV, HGV, and?)

62 Hepatotropic viruses Table 37.4

63 Acute viral Gastroenteritis Food-borne and waterborne diseases Inflammation of stomach or intestines important disease of infants and children, leading cause of childhood death in developing countries probably spread by fecal-oral route Figure Rotavirus

64 Enterovirus 71 (1998~ ) An RNA virus Typical cold symptoms mild enteric disease hand, foot, and mouth disease CNS (central nervous syndrome) diseases

65 Zoonotic (Animal-Borne) Diseases human viral infections in animal reservoirs before transmission to and between humans many are on Select Agents list as potential bioweapons Ebola and Marburg viruses hantaviruses Lassa fever virus Nipah virus bio-safety P4 level

66 Filoviridae- Marburg and Ebola virus Ebola hemorrhagic fever A severe and often fatal disease in human or nonhuman primates 1 st recognition subtypes: Humans- Ebola-Zaire, Ebola- Sudan, and Ebola-Ivory Coast Nonhuman Primates- Ebola- Reston An RNA virus -1967, Marburg -1976, Ebola/Zaire 66

67 Hantavirus Pulmonary Syndrome An outbreak occurred in May 1993 in the Four Corners (New Mexico, Arizona, Colorado, and Utah) The deer mouse- the principal carrier (climate changes) Navajo Indian No person to person spread cause hemorrhagic fever 67

68 Smallpox (Variola) smallpox virus A re-emerging disease: Biological weapon transmitted by aerosol or contact humans are only reservoir 30% fatality 68