5 Basic Virology

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    PART III Basic Virology

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    Basic Concepts ofBasic Concepts ofVirusesViruses

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    Viruses : non-cellular organisms

    General Characteristics of Viruses :

    1. Smallest: 20300 nm, most were too small to beseen with the light microscope ;

    2. Simplest: non-cellular entity, contain DNA or RNA

    and protein. 3. Obligate intracellular parasites: growing only

    within the living cells.

    4. Self-replication :Once it has invaded a cell it is ableto direct the host cell machinery to synthesize newintact infectious virus particles.

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    Significance ofignificance of Studingtuding

    Virology for ife Science

    irology for ife Science

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    I. Viruses and infectious

    diseases

    New presented viruses and viral infectionstill harm peoples health

    AIDS

    HBV infection

    Influenza

    SARS

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    Virus and Cancer

    Infections Cause of Cancer

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    Size : 20 -- 300 nm( the most virus150 nm );

    Shape: The commonest sape ---- small spherical virusOthers ----- filamentous, brick, bullet

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    Size and Shape

    Virion: The basic infectious particle of avirus is known as the virion.

    Simple virion (naked virus):a nucleic acid and capsid

    Complex virion (enveloped virus):

    nucleic acid , capsid, and envelope

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    Structure

    Viruses contain: nucleic acid genome (RNA or DNA)

    protective protein coat (called thecapsid)

    viral envelope( enveloped virus)

    Non-structural protein

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    (I) Nucleic acid1. Single kind: consist of DNA or RNA

    ( never both).

    1) DNA :

    single-stranded DNA (ssDNA) :

    double-stranded DNA ( dsDNA ): --- thecommonest type of nucleic acid in viruses ofhuman.

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    2) RNA:

    double-stranded RNA (dsRNA) : single-stranded RNA (ssRNA):

    --- the commonest type of nucleic acidin viruses of human..

    ssRNA : is the same as the viral

    mRNA , can direct as viral mRNA -ssRNA : as a template transcribecomplementary mRNA

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    2. Function:

    1). viral genome

    : viralnucleic acid conteins all geneticinformation of the virus.

    2). possess infectiousness

    -- infectious nucleic acid

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    infectious nucleic acidinfectious nucleic acid : infectious nucleic acid is purified viral

    DNA or RNA(without any protein) that can

    carry out the entite viral growth cycle andresult in the production of complete virusparticles. such as the genomes of dsDNAviruses and +ssRNA viruses.

    such as: DNA virusdsDNA;

    RNA virus (+ssRNA) ;

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    (II) . Capsid

    protein coat ,1. capsid is composed of distinct

    morphologic units---- capsomeres

    --- icosahedral symmetry:

    --- helical symmetry:

    --- complex symmetry:

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    Capsomeres

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    IcosahedronIcosahedron and symmetryand symmetry

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    2. Function:

    1) protection --- protect viral nucleicacid from enzymic action.

    specific binding sites --- mediate theviral attachment

    antigenicity ---- important antigens

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    (III). Envelope ():

    1. Consists of lipid bilayer and glycoprotein:

    lipid --- derived from host cell membrane.

    Glycoprotein --- coded by the viral genome.

    Spikes() --- virus-encoded glycoproteinprotruding from lipid bilayer, which areimportant for adsorption and entry into thehost cell.

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    2. Functions: 1) as the binding sites -- the spikes of

    enveloped virus attach to host cell receptors

    2) have antigenicity ---- envelopeglycoproteins are also important antigens

    3) confers instability on the virus---enveloped viruses are more sensitive to heatand lipid solvents.

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    Spikes (

    )

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    (IV) . Non-structural protein:

    Code by virus; it is not the composition ofvirion. It can exist in virion and infected cell.

    (1) viral enzymes:

    such as RNA-dependent RNA polymerase ortranscriptase .

    (2) specific viral protein:

    such as : transformation protein of tumorvirus.

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    III. Viral Multiplication

    Replication: The process ofintracellular viral multiplication,consisting of the synthesis of

    PROTEINS; NUCLEIC ACIDS; andtheir assembly into a new

    infectious.

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    I. Replication cycle

    :

    adsorption

    penetration

    uncoating

    biosynthesisassembly and release

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    (I) Replication cycle

    :1. adsorption ():

    The proteins on the suface of the virion

    (called virion attachment proteins

    VAP) attach to specific receptors on the

    host cell surface.Such as: HIV(gp120) --- Helper Tlymphocytes(CD4 protein)

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    2. penetration

    :virus enter the cells.

    Entry of Naked viruses:endocytosis

    Entry of enveloped virus :

    simple fusion of membranes

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    3. uncoating

    Rapid change from stable structure to

    release of genome

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    4. Biosynthesis: Geneexpression & Genome Replication

    Synthsis of viral proteins

    Synthsis of viral nucleic acid

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    4.1 dsDNA viruses:

    Replicate in the nucleus, use the host cell DNA

    dependent RNA polymerase to synthesize theirmRNA

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    4.1 dsDNA viruses: replicate in the nucleus use the host cell DNA dependent RNA polymerase to

    synthesize their mRNA

    (1) early transcription and translation: early mRNA ( use cell RNA polymerase ) early proteins ( non-structural proteins): --- enzyme which is necessary for viral

    replication. --- specific viral proteins: regulation protein

    ()transformation protein.

    .

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    (2) viral DNA replication : (3) late transcription and translation :

    late proteins (structural proteins ): ---- capsid protein and

    envelope protein

    dsDNA

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    dsDNA

    + -

    RNA

    mRNA

    (enzymes)DNA

    mRNA

    (structure proteins )

    dsDNA

    DNA

    + - + -

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    4.2 RNA viruses ( three kinds) :

    (1)+ssRNA viruses:

    The +ssRNA itself can direct as viralmRNA .

    (+)ssRNA

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    (+)ssRNA

    mRNA

    + ( RI )

    RNA

    RNA

    -

    -

    +ssRNA

    mRNA ,

    +ssRNA

    RNA

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    (2) -ssRNA viruses:

    Use the virion RNA polymerase to

    synthesize viral mRNA.

    ( )ssRNA

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    ()ssRNA

    RNA

    -

    -+

    mRNA

    ssRNA

    RNA

    + ( RI )

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    (3) Retroviruses:

    use the virion reverse transcriptase tosynthesize a DNA cope of the viral RNA

    genome; use the host cell RNA polymerase to

    synthesize the viral mRNA

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    (3) Retroviruses:

    +ssRNAReverse transcriptase

    cDNA

    Proviral DNA (dsDNA)

    Integrated into host chromosome

    Viral mRNA transcription Viral RNA replication

    +ssRNA

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    RNADNA

    dsDNA

    DNA(provirus)

    DNA

    ++

    mRNA

    + ssRNA

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    RNA Virus:

    The mRNA is translated into a singlepolypeptide (polyprotein), which iscleaved.

    Be cleaved by a virus-coded proteaseinto various proteins.

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    5. assembly and release

    Assembly: --- Assembly of DNA virus occurs in the

    nucleus

    --- Assembly of RNA virus occurs in thecytoplasm

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    Virus budding

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    (II ) Unnormal multiplication:

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    (II.) Unnormal multiplication:

    3. Interference

    The infection of cell by a virus results inthat cell becoming resistant to infection by

    other viruses.

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    Section

    Viral heredity and variation

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    Viral genomeViral genome

    hereditary substance:

    DNA ; or RNA

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    EXAMPLES of Mutant

    Mutant( )

    --- temperature sensitive mutant, ts

    --- drug-resistant mutant

    Temperature-sensitive mutant (ts):

    permissive temperature: 28

    ~35

    non permissive temperature: 36

    ~40

    ts mutant -- attenuated mutant ( vaccine mutant )

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    RecombinationRecombination &&ReassortmentReassortment

    Recombination:

    the exchange of genes between two related

    viruses which infected the same cell. ( active virus-active virus; active virus-inactive virus).

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    Reassortmentexchange of genetic material between

    two segmented viruses which infected the

    same cell.

    Gene integrationGene integration

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    Gene integrationGene integration

    Viral genome insert into host cell genome

    e.g. tumor viruses

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    Interaction of viral genetic ProductsInteraction of viral genetic Products

    --------nnongeneticComplementation()genetic production

    reactivation between two viruses ( one or both of which

    may be defective)

    Phenotypic mixing(): If two different

    viruses infect a cell, progeny viruses may contain coatcomponents derived from both parents and so they willhave coat properties of both

    parents.

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    Section 4Effects of Physical and Chemical Agents

    on Viruses

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    Resistance:

    low temperature - 196pH 59

    antibioticSensitivity

    high temperature: >50

    radiation and UV

    lipo-solvent : enveloped virus

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    Section 5Section 5

    Classification of AnimalClassification of AnimalVirusesViruses

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    UNCONVENTIONAL AGENTS

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    UNCONVENTIONAL AGENTS

    Subvirus : refer to the kind of infectiousfactor which is smaller than virus.

    1. viroid(

    ) and virusoid(

    )

    --To contain RNA only

    --To have only been shown to beassociated with plant disease.

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    2. prion (

    )

    prions are infectious particles encoded bygene of normal host cells , they arecomposed solely of protein; they areimplicated as the cause of certain slow virus

    disease called transmisslble apongiformencephalopathies(TSEs) in animals andhuman.

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    cellular PrP, PrPc

    ()---- normal

    scrapie prion protine,

    PrPsc ()---- pathogenic