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Chapter 18Eucaryotic Viruses and other
acellular infectious agents11-25-200811-26-2008
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Taxonomy of Eucaryotic Viruses
most of the ~5,000 known viruses infect eucaryotic organisms Virus classification by the ICTV
Genome structureReplication strategyMorphologyGenetic relatedness
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Viruses that Infect Vertebrates
Figure 18.1
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Reproduction of Animal Viruses
adsorptionpenetration and uncoatingreplication of virus nucleic acidssynthesis and assembly of virionsvirion release
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Table 18.1
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Penetration and Uncoating
fusion of envelope with host cell membrane
Fig 18.4
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Endocytosis – enveloped virus
Figure 18.4 (b)
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Endocytosis – naked virus
Figure 18.4 (c)
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Replication and transcription in DNA Viruses- Herpes simplex virus I
uses host RNApolymerase forsynthesis of viralmRNA
uses virus-encoded DNApolymerase forgenome replication
Figure 18.6
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Poxviruses
large, morphologically complex double-stranded DNA (dsDNA) virusesvirion carries DNA-dependent RNA polymerase that synthesizes early mRNA
encodes DNA polymerase and other enzymes needed for DNA replication
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Hepadnaviruses- HBV
circular, partial dsDNA genometranscribed by host RNAP
generates several mRNA moleculesone for pregenome RNA others encode polymerase with reverse transcriptase activity
pregenome converted to dsDNA by virus polymerase (+RNA -DNA 2S DNA)
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Replication and Transcription in RNA Viruses
very diverse reproductive strategiesfour general modes of replication and transcription
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Pico-RNA
Para- and ortho-Myxo- affinity to mucin
Respiratory-enteric-orphan
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Assembly of Virus Capsids
late genes direct capsid protein synthesis which spontaneously self-assemble to form the capsidduring icosahedral virus assembly empty procapsids form first, nucleic acid are then insertedassembly of envelope viruses
in most cases, similar to assembly of naked viruses
site of morphogenesis varies
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Figure 18.2
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Virion Release
naked virusesusually by lysis of host cell
envelope virusesformation of envelope and release usually occur concurrently (budding)
virus-encoded proteins incorporated into host membranenucleocapsid buds outward and is surrounded by modified host membrane
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Release of influenza virus by budding
Figure 18.11
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HIV release by budding
Figure 18.12 (a)
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Mechanisms of host cell damage and cell death
inhibition of host DNA, RNA, and protein synthesislysosome damage
causes release of hydrolytic enzymes alteration of plasma membrane
lead to attack of host by immune systemlead to cell fusion, forming syncytium
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Other mechanisms…toxicity from high concentrations of viral proteinsformation of inclusion bodies
can disrupt cell structurethe Negri bodies in rabies infected neurons
chromosomal disruptionstransform host cell into malignancy
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Types of viral infections (Fig. 18.3)
acute infectionsrapid onset and relatively short duration
persistent infections- last many yearsChronic infection, e.g, HBV infectionLatent infection, e.g., Herpes virus infection-
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Types of persistent infections
chronic virus infectionvirus almost always detectableclinical symptoms mild or absent for long periods
latent virus infectionvirus stops reproducing and remains dormant for some timeduring latency, symptoms, antivirus-antibodies, and viruses are not detectable
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Possible causes of persistent infections
integration of viral genome into host genomedecrease in antigenicity of virusmutation to less virulent and slower reproducing form
defective interfering (DI) particle – deletion mutant that cannot reproduce and slows reproduction of normal virus
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Slow virus diseases
Symptoms take years to emergesubacute sclerosing panencephalitis caused by measles virusHIV infectionsPrion
Prion
A small proteinaceous infectiousparticlePasses through the filter (100 nm)and still transmits diseaseresistant to a wide range of chemical and physical treatment
inactivated at 121oC 1 h
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Prion-caused degenerative diseases
Scrapiebovine spongiform encephalopathy (BSE) or mad cow diseaseCreutzfeldt-Jakob disease (CJD) and variant CJD (vCJD)Kuru
Scrapie- cause intense itching- The prototype of prion- A natural progressive brain disease
Kuru- “shivering” or “ trembling”
1950, occurred in the Fore tribe of New Guinea highlands
Related to the cannibalistic practicesBlurred speech, silly smiles, and dementia
lose the ability to walk, talk, and see
The 1st 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!
Creutzfeldt-Jakob disease (CJD)
The human form of mad cow diseaseBSE (Bovine Spongiform encephalopathy)
Identified by Creutzfeldt and Jakob (1920)A progressive fatal neurodegenerative disease Usually aged between 50~75Characterized by seizures, massive in-coordination, dementia
Transmission of CJDInjection with contaminated growth hormoneTransplantation of contaminated corneasContact 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)
Inheritable CJD- prnpA Gerstmann-Straussier-Scheinker syndromeA 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
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Current Modelof Disease Production by Prions
PrPC (prion protein): “normal” form PrPSc : abnormal form
entry of PrPSc into animal brain causes PrPC to change its conformation to abnormal formthe newly produced PrPSc convert more to the abnormal forminteractions between PrPSc and PrPC
crosslinking of PrPC neuron loss
The 2nd Nobel prize-Prion pathogenesis
PrPsc binds to the normal PrPc
on the cell surface, causing it to be processed into PrPsc - a replicating protein, to be released from the cell, and to be aggregated as amyloid-like plaques in the brainVacuolated neurons (loss of function and lack of an immune response)
1997, Stanley Prusiner(1942~) for showing that PrPsc is sufficient to cause disease
Director of institute of neurodegenerative disease UCSF
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Viruses and Cancer
tumorgrowth or lump of tissue
neoplasiaabnormal new cell growth and reproduction due to loss of regulation
anaplasiareversion to a more primitive or less differentiated state
metastasisspread of cancerous cells throughout body
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Carcinogenesis
complex, multistep processoften involves oncogenes
cancer-causing genesmany involved in regulation of cell growth and differentiation
some viruses contribute to carcinogenesis
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Viruses implicated in human cancers
Epstein-Barr virus Burkitt’s lymphomanasopharyngeal carcinoma
Hepatitis B virus liver cancer
Hepatitis C virus liver cancer
Human herpesvirus 8 HIV
Kaposi’s sarcoma
human papillomavirus cervical cancer
HTLV-1 and HTLV-2 leukemia
hepatoma
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Possible mechanisms by which viruses cause cancer
carry oncogene into cell and insert it into host genomealtered cell regulation due to changes in kinase activity or production of regulatory proteinsinsertion of promoter or enhancer next to cellular oncogene
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Chapter 37
Human Diseases Caused by Viruses
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Airborne Diseases
when human is source, airborne viruses are propelled from respiratory tract by coughing, sneezing, or vocalizing
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Chickenpox (Varicella)
caused by varicella-zoster virusresults from initial infectionAttenuated vaccine
Figure 37.1
Shingles (herpes zoster)
postherpetic neuralgiareactivated form of chickenpox
Figure 37.2
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Flu or common cold
clinical manifestationschills, fever, headache, malaise, and general muscular aches and painsrecovery usually within 3 to 7 daysoften leads to secondary infections by bacteriarhinitis, tonsillitis, laryngitis, bronchitis, and pneumonia
treatment, prevention, and controlsymptomatic/supportive therapyinactivated virus vaccine
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Influenza (Flu) by influenza virusOrthomyxovirus (segmented virus)
Classified into A, B, and C groups16 HA and 9 NA
Influenza Pandemics1918, HswN1 (Spanish flu)
50~ 100 million moratlity1947, H1N1 1957, H2N2 (Asian flu)1968, H3N2 (Hong Kong flu)1977, H1N1 (Russian flu)Avian flu- H5N1(1997~)
Generation of a reassortant virus - broad host range and segmented genome
Reassortant virus
Avian flu virusH9N2 (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
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SARS (Severe Acute Respiratory Syndrome)
An emerging disease cause by coronavirusFlu-like syndromeVaccine target?- Virus of the year (2002-2003)
Where is the SARS virus?? Box18.1- a mutation in spike protein
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3 groups coronaviruses: groups 1 and 2: mammalian virusesgroup 3 contains only avian viruses
Classified into distinct species by host range, antigenic relationships, and genomic organization
Classification of coronaviruses
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Phylogenetic analyses of SARS-CoV sequences
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Measles (Rubeola)
caused by measles virussubacute sclerosingpanencephalitis
rare progressive degeneration of central nervous system caused by measles virus
treatment, prevention, and control
symptomatic/supportive therapyattenuated measles vaccine
MMR vaccine (measles, mumps, rubella)
Figure 37.3
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Mumps
caused by mumps viruspleomorphic, enveloped virushelical nucleocapsidnegative strand RNA
Figure 37.4
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Rubella (German Measles)
caused by rubella virusssRNA virus
spread by respiratory dropletscongenital rubella syndrome
infection of pregnant women in first trimesterfetal death, premature delivery, and/or congenital defectslive attenuated vaccine: MMR- measles, mumps, rubella
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 virus2006 CDC estimation:
~ 1 million HIV infections in USAConverging HIV and MDR-TB (multi-drug resistance tuberculosis) Outbreaks Worsen
HIV
Figure 37.7
TransmissionAcquired 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 orderhomosexualsintravenous drug usersheterosexuals with drug users and prostituteschildren of infected mothers and breast-fed infantstransfusion patients and transplant recipients
• Once inside host, HIV gp120 envelope protein binds to host CD4+glycoprotein plasma membrane receptor on CD4 + cells
HIV pathogenesis
Figure 37.8
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 centuryretrovirustheories on origin of disease
HIV-1 evolved from chimp virus SIVcpzuse of human blood products in chimps infected animals with HIV-1 precursor that evolved into SIVcpz
Course of Disease
some patients rapidly develop clinical AIDS; die within 2-3 yearssome patients remain relatively healthy for at least 10 years post infectionin majority of patients HIV infection progresses to AIDS in 8-10 years
CDC classification for HIV-related stages
AIDS- fourth and last stageimmune system no longer able to defend against virus
definition of AIDSall 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
AIDS-related cancers
Kaposi’s sarcomacaused by human herpesvirus 8
carcinoma of mouth and rectumB-cell lymphomas
AIDS-related central nervous system disease
headaches, fever, subtle cognitive changes, abnormal reflexes, and ataxiadementia and severe sensory and motor changes observed in advanced casesautoimmune neuropathies, cerebrovasculardisease, and brain tumors are common
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Viral Hepatitishepatitis
inflammation of livercaused by different viruses
Epstein-Barr virus (EBV)cytomegalovirus (CMV)
cause mild, self-resolving diseaseno permanent hepatic damagesigns and symptoms include fatigue, nausea, and malaise
hepatotropic viruses (HAV, HBV, HCV, HDV, HEV, HGV, and ?)
Hepatotropic viruses
Table 37.4
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 countriesprobably spread by fecal-oral route
Figure 37.21 Rotavirus
Enterovirus 71 (1998~ )
An RNA virusTypical cold symptoms
mild enteric diseasehand, foot, and mouth disease
CNS (central nervous syndrome) diseases
Zoonotic (Animal-Borne) Diseases
human viral infections in animal reservoirs before transmission to and between humansmany are on Select Agents list as potential bioweapons
Ebola and Marburg viruseshantavirusesLassa fever virusNipah virus
bio-safety P4 level
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Filoviridae- Marburg and Ebola virus
Ebola hemorrhagic fever A severe and often fatal disease in human or nonhuman primates1st recognition- 19764 subtypes:
Humans- Ebola-Zaire, Ebola-Sudan, and Ebola-Ivory CoastNonhuman Primates- Ebola-Reston
An RNA virus-1967, Marburg
-1976, Ebola/Zaire
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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 IndianNo person to person spread
cause hemorrhagic fever
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Smallpox (Variola)smallpox virusA re-emerging disease: “Biological weapon”
transmitted by aerosol or contact
humans are only reservoir30% fatality