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Foundations of Disease > Exam 1: Intro to Virology > Flashcards

Exam 1: Intro to Virology Flashcards

1
Q

Viruses

Overview

A
  • Obligate intracellular existence
    • Dependent on host cells for energy, metabolism, protein synthesis, and replication
  • Not visible by LM ⇒ 20-300 nm diameter
  • Ultimate parasites
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2
Q

A single virus is called a…

A

virion

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3
Q

Nucleic Acid

Structure

A
  • Innermost virion component
  • DNA or RNA ⇒ not both
  • Linear or circular
  • Single or double stranded
  • Segmented or non-segmented
    • More segmented = more complex lifecycle
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4
Q

Capsid

A

Outermost covering of viruses

protomers ⇒ capsomers ⇒ capsid

Functions:

  • Protection
    • Against DNase and RNase
  • Attachment
    • For non-enveloped viruses
  • Antigenicity
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5
Q

Protomers

A

Structural unit of the capsid.

Viral proteins.

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6
Q

Capsomers

A

Morphological unit of the capsid.

Formed from one or more types of protomers.

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7
Q

Capsid Symmetry

A

Determines by the organization of capsomers.

Used for classification.

  • Helical
  • Icosahedral
    • Pentons ⇒ always surrounded by 5 other capsomers
    • Hexons ⇒ always surrounded by 6 other capsomers
  • Complex
    • Seen in POX viruses
    • Rare
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8
Q

Nucleocapsid

A

Nucleic acid + capsid

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9
Q

Naked viruses more stable to ___ than enveloped viruses.

A

environmental stress

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10
Q

Envelope

A
  • Derived from host lipid bilayer
    • Protects nucleocapsid
  • Contains peplomers (“spikes, glycoprotein spikes”)
    • Virus-encoded
    • Functions
      • Attachment
      • Entry
      • Antigenicity
      • Enzymatic activity
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11
Q

Viral Budding

A

How a virus become enveloped:

  1. Virus encoded proteins become associated with host plasma membrane
    • Can get membrane from organelles also
    • Exit through exocytosis
  2. Glycoprotein spikes incorporated into membrane
  3. Viral nucleocapsid assembled near the membrane
  4. Budding begins
  5. Viral spikes further inserted into membrane
  6. Buding completed releasing a free virion
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12
Q

Virus

Classification

A

Only 6 ways to classify:

  1. Nucleic acid type
    • DNA or RNA
  2. Nucleic acid structure
    • SS vs DS
    • Circular vs linear
    • Segmented or non-segmented
  3. RNA polarity ⇒ for RNA viruses only
    • Positive sense vs negative sense
  4. Enveloped or Naked
  5. Symmetry
    1. Helical, icosahedral, or complex
  6. Strategy for genome replication
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13
Q

Size & Morphology

A
  • Differ widely in shape and size
    • Picornavirus ⇒ 28 nm, size of a ribosome
    • Poxvirus ⇒ 250x300 nm, ⅓ size of mitochondrion
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14
Q

RNA Virus

Classification

A
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15
Q

RNA Viruses

Families

A
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16
Q

DNA Virus

Classification

A
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17
Q

DNA Viruses

Families

A
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18
Q

Viral Replication

Steps

A
  1. Recognition of target cell
  2. Attachment
  3. Penetration
  4. Uncoating
  5. Macromolecular synthesis
  6. Assembly of virus
  7. Budding of enveloped virus
  8. Release of virus
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19
Q

Recognition and Attachment

A

“Adsorption”

  • Recognition
    • Enveloped viruses ⇒ use peplomers aka viral glycoprotein or spikes
    • Nake viruses ⇒ use capsid proteins
  • Attach to cell surface via receptors or co-receptors
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20
Q

Tropism

A

Use of different receptors or co-receptors to attach and enter cells.

Ex. HIV is T-cell tropic

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21
Q

Penetration

A

Translocation of entire viron or portion of viron.

  • Enveloped viruses
    • Receptor mediated endocytosis
    • Fusion
  • Naked viruses
    • Receptor mediated endocytosis
    • Directly cross plasma membrane
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22
Q

Uncoating

A

Release of viral nucleic acid from capsid.

Makes genome accessible to cellular machinery.

  • Can occur simultaneously with penetration or with receptor induced conformational changes
  • Some naked viruses need host enzymes to remove capsid
  • Three strategies:
    1. At plasma membrane
    2. Within endosomes
    3. At nuclear membrane
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23
Q

Macromolecular Synthesis

A

Varies depending on type of viral genome.

Tightly regulated through expression of early and late gene products to regulate host cell cycle.

Generally:

  1. Early mRNA and non-structural protein synthesis
  2. Replication of viral genome
  3. Late mRNA and structural protein synthesis
  4. Post-translational modification of protein
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24
Q

Viruses can use their molecular machinery to help with ___ but cannot perform ___.

A

DNA/RNA replication

protein synthesis

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25
Q

Most RNA viruses replicate in the ___ except for ___ and ____.

A

cytoplasm

Exceptions:

  • Influenza ⇒ replicates in the nucleus
  • Retroviruses ⇒ integrates DNA copy into host chromosome
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26
Q

RNA-dependent RNA-Polymerases

(RdRp)

A
  • Not present in eukaryotic cells
  • Viral encoded
    • Can be produced within host cells for SS ⊕-sense RNA viruses
    • Must be brought along within capsid for SS ⊖-sense RNA viruses
  • Other viral proteins may be required as accessory factors for RNA synthesis
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27
Q

RNA Processing

A

Addition of 5’ cap and 3’ poly-A tail required.

Neccessary for recognition by host translation machinery.

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28
Q

Examples of SS ⊕-sense RNA viruses are…

A

Poliovirus & West Nile Virus

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29
Q

SS ⊕-sense RNA viruses

Protein Synthesis

A
  • Functions directly as mRNA
  • Translated by cellular ribosomes into viral proteins
    • Can be translated as one large polyprotein
    • Cleaved by viral proteases to make individual proteins
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30
Q

SS ⊕-sense RNA viruses

RNA Production

A
  • Parental ⊕ ssRNA replicated by viral RNA-dependent RNA-polymerase (RdRp)
  • Makes ⊖ ssRNA
    • Used by RdRp to make more ⊕ ssRNA
      • Serves as additional mRNA for protein synthesis by cellular ribosomes
      • Packaged into new virions
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31
Q

Examples of SS ⊖-sense RNA viruses includes…

A

Influenza & Measles virus

32
Q

SS ⊖-sense RNA Viruses

Protein Synthesis

A
  • ⊖ ssRNA ⇒ ⊕ mRNA by viral RdRp
  • Translated into proteins by cellular machinery
33
Q

SS ⊖-sense RNA Viruses

RNA Production

A
  • ⊖ ssRNA acts as a template to make ⊕ ssRNA
    • Virus must carry RdRp within capsid
    • Eukaryotes cannot recognize ⊖ ssRNA
  • ⊕ ssRNA used as template by RdRp
    • Makes more ⊖ ssRNA for new virions
34
Q

Examples of DS RNA viruses are…

A

Reoviruses & Rotaviruses

35
Q

DS RNA Virus

Protein Synthesis

A
  • Cannot function directly as mRNA
  • Viral RdRp transcribes a ⊕ mRNA using ⊖ strand of RNA as template
    • Genome always segmented
    • Each segments transcribed to produce a unique mRNA
  • ⊕ mRNA used by host machinery for protein synthesis
36
Q

DS RNA Virus

RNA Production

A
  • Viral RdRp transcribes a ⊕ ssRNA using ⊖ strand of parental dsRNA as template
  • ⊕ ssRNA used by RdRp to produce complementary ⊖ strand
  • Makes new copies of parental dsRNA
37
Q

DNA Virus Replication

Overview

A
  • Cellular + viral proteins needed for viral DNA replication
    • Except poxviruses ⇒ do not use cellular components
  • Some use celluar DNA polymerase
    • Parvoviruses & Papovaviruses
  • Some encode their own viral DNA polymerase
    • Adenovirus & Herpes viruses
  • Some induce cells to enter into S phase
    • Papovacirus & Adenovirus
  • Some inhibit cellular DNA synthesis
    • Herpes viruses
38
Q

Example of SS DNA virus is…

A

Parvoviruses

39
Q

Single-stranded DNA Virus

Protein Synthesis & DNA Replication

A
  • Replication occurs in host cell nucleus
    • Uses host enzymes
  • Viral DNA serves as template for:
    • mRNA
      • Translated into proteins by host machinery
    • Intermediate dsDNA
      • Used as template to make more ssDNA for new virions
40
Q

Examples of DS DNA viruses are…

A
  • Adenoviruses
  • Herpes viruses
  • Papillomavirus
  • Poxviruses
41
Q

dsDNA virus genome can be…

A

circular or linear

42
Q

Double-stranded DNA Virus

Protein Synthesis

A
  • dsDNA used by host RNA polymerase to make mRNA
  • mRNA produced contains exons and introns
  • mRNA synthesized using multiple overlapping reading frames
    • Reduces amount of DNA needed to encode viral proteins
43
Q

Double-stranded DNA Virus

DNA Replication

A
  • Typically occurs in host nucleus
  • Uses either host or viral DNA polymerase
    • Smaller viruses use host machinery
      • Not enough room in the capsid
      • Ex. Parvociruses & Papovaviruses
    • Larger viruses code for their own DNA pol
      • Ex. Adenovirus & Herpes viruses
  • Cellular + viral proteins needed for viral DNA replication
44
Q

___ replicate in the cytoplasm using their own enzymes for nucleic acid replication.

A

Poxviruses

45
Q

RNA Viruses

with

DNA Intermediates

A

Ex. retroviruses:

  • SS ⊕-sense RNA acts as template to make viral DNA
    • By viral RNA-dependent DNA polymerase (reverse transcriptase)
  • DNA integrated into host genome
  • Transcribed to mRNA by host machinery
    • Translated into viral proteins
    • Used as ssRNA for new virions
46
Q

Asssembly, Budding, and Release

A
  • Final steps in viral replication cycle
  • Assembly often occurs spontaneously
  • Release
    • Naked viruses usually released with cell lysis
      • Can be released through exocytosis
    • Enveloped viruses usually released by budding
  • Some require further virion maturation before they acquire infectious potential
    • Ex. HIV-1 needs proteolytic processing of virion proteins in released particles
47
Q

Viral

Growth Curve

A

Eclipse period ⇒ intracellular growth period

Exponential growth period ⇒ detectable # of viruses significantly increase through cell lysis, exocytosis, or budding

Yield per cell ⇒ difference between infectious load and viral count after one round of division

48
Q

Viral Disease

Basic Progression

A
  1. Acquisition ⇒ entry of the virus into the body of the host
  2. Initiation of Infection ⇒ binding and entry of the virus into primary host cell
  3. Activation of innate protections
  4. Incubation period ⇒ period when the virus is amplified and may spread to a secondary site
    • Asymptomatic
    • Prodrome ⇒ non-specific early symptoms
    • Symptoms ⇒ caused by tissue damage and systemic effects
  5. Replication ⇒ causes characteristic disease symptoms
  6. Immune response
    • Limits infection and clears the virus
    • May contribute to disease ⇒ immunopathogenesis
  7. Contagion ⇒ virus production in tissues that facilitates spread of the virus to other people
  8. Resolution
    • Clearance of infecting virus
    • Or persistent infection/chronic disease ⇒ viral latency
49
Q

Host

Viral Entry Routes

A
  1. Inhalation
  2. Skin breaks
  3. Mucous membranes
    • Eyes, respiratory tract, mouth, etc
    • Tears, mucus, ciliated epithelium, stomach acid, bile, sIgA protects
50
Q

Respiratory Tract

Entry

A
  • Enter via inhalation
  • Most important entry site for viruses
  • Some remain localized
    • Influenza, rhinovirus, coronaviruses
  • Some spread systemically
    • Mumps, measles, rubella
51
Q

GI Tract

Entry

A
  • Enter via ingestion
  • Infections only caused by non-enveloped viruses
    • Resistant to degradation by low pH of stomach
    • Ex. rotaviruses
  • Some can disseminate beyond the GI tract
    • Neurovirulent poliovirus
    • Some other enteroviruses
      • Coxsackie
      • ECHO
52
Q

Skin Entry

A
  • Enter via skin abrasions, animal bite, arthropod vector, injection
  • Only localized viral skin infection are warts caused by papillomavirus
  • Disseminated infections caused by:
    • Herpesvirus
    • Rabies virus
    • Hepatitis B, C, D
    • HIV-1 and 2
53
Q

Genital Tract

Entry

A
  • Causes local lesions on genitalia and perineum
    • Herpes simplex
    • Papillomaviruses
  • No local lesions but disseminate to target organs
    • Hepatitis B
    • HIV
54
Q

Cellular Susceptibility

Factors

A
  • Plasma membrane receptors
    • The more ubiquitous the receptor, the wider the host range
    • Examples:
      • Epstein-Barr virus ⇒ CR2 on B cells
      • HIV ⇒ CD4 on T cells
      • Rabies ⇒ ACh receptors
  • Intracellular proteins
    • Use cellular transactivator proteins and enzymes for replication
55
Q

Host Susceptibility

Factors

A
  • Age
    • Most are more virulent in young or old
  • Nutrition
    • Malnourishment increases susceptibility
  • Pregnancy
    • Many infections more severe during pregnancy
    • Likely due to mild immunosuppression
  • Genetics
    • ∆ host-virus interactions
    • Certain MHC molecules do not present some viral Ag
56
Q

Incubation Period

A

Time difference between infection and first manifestation of disease.

  • Short if viral infection localized
  • Much longer if systemic spread required to reach target organ
  • Varies enormously due to:
    • Viral characteristics
    • Size of inoculum
  • Types:
    • Asymptomatic
    • Prodrome ⇒ nonspecific early sx
    • Symptomatic ⇒ caused by tissue damage and systemic effects
57
Q

Viral Dissemination

A
  • Local spread on epithelial surfaces
  • Subepithelial invasion / Lymphatic spread
  • Blood transport ⇒ viremia
58
Q

Local Spread

A
  • Local spread on epithelial surfaces
    • Replicate in epithelial cells @ site of entry
    • Spread to neighboring cells
      • Fluids transport virus along epithelial surface
    • Shed into the environment
59
Q

Subepithelial invasion / Lymphatic spread

A
  • Gains access through:
    • Tissue damage
    • Phagocytosis
    • Transport past mucoepithelial layers of MM
  • Picked up by macrophages
    • Brought to the local lymphatics
60
Q

Viremia

A

Viremia ⇒ the first time the virus enters the blood.

Often procedes delivery of virus to target tissues.

  • Gains access through:
    • Tissue damage
    • Phagocytosis
    • Transport past mucoepithelial layers of MM
  • Transported free in plasma or in WBCs
    • Phagocytosed viruses inactivated, replicate, or delivered to other tissues
61
Q

Secondary Viremia

A

Amplification of infection by viral replication in macrophages, endothelium, or liver.

The second time the virus enters the blood after already reaching target tissues.

62
Q

Viral Pathogenesis

Mechanisms

A

Viruses cause disease by:

  • Breaching the body’s natural defensive barriers
  • Evading the host’s immune response
  • Directly killing infected cells
  • Triggering destructive immune and inflammatory processes
63
Q

Cytolysis Mechanisms

A
  1. ∆ cellular macromolecular synthesis
  2. Disruption of lysosomes
  3. ∆ cell membrane permeability
  4. Toxic effects of viral products
  5. Chromosomal aberrations
  6. Enhanced necrosis
  7. Apoptosis
  8. Cell fusion ⇒ syncytia
64
Q

Viral Pathogenesis

Determinants

A
  1. Interaction of the virus with target tissue
  2. Cytopathic activity of the virus
  3. Host protective responses
  4. Immunopathogenesis
65
Q

Host : Virus

Interactions

A
  1. Access of virus in the body
  2. Viral stability
    • Temp & pH
  3. Ability to cross skin or mucous epithelial cells
  4. Ability to establish viremia
  5. Target tissue type
    • Specificity of viral attachment proteins
    • Tissue-specific expression of viral receptors
66
Q

Cytopathic Activities

A
  1. Efficiency of viral replication & gene expression
    • Optimum temp for replication
    • Permissiveness of cell for replication
  2. Cytotoxic viral factors
  3. Inhibition of cellular processes
  4. Accumulation of vial proteins and structures (inclusion bodies)
  5. Transformation
67
Q

Host Protective Response

A
  1. Innate immunity
    • IFN, NK cells, Mφ
  2. Adaptive immunity
    • T-cells, Ab
  3. Viral evasion of host immune response
68
Q

Immunopathology

A
  • Interferon ⇒ flu-like systemic symptoms
  • T-cell responses
  • Antibodies
  • Inflammatory responses
69
Q

Shedding / Release

A
  • Necessary to maintain viral infection in populations
  • Occurs at different stages depending on viral infection
    • Localized infections ⇒ same body openings for entry and exit
    • Generalized infections ⇒ greater variety of shedding mechanisms
      • Nasopharyngeal secretions
      • Blood
      • Fecal matter
      • SKin
    • Persistent infections ⇒ more common with latent infections, virus continuously made
      • Urine
      • Blood
      • Saliva
      • Genital secretions
  • Does not occur when humans are dead-end hosts
    • Rabies
    • Eastern and western equine encephalitis
70
Q

Epidemiology

A

The study of the spread of disease through a population

71
Q

Viral Transmission

Mechanisms

A
  1. Aerosols
  2. Food/water
  3. Fomites ⇒ contaminated objects
  4. Direct contact with secretions ⇒ saliva, semen
  5. Sexual contact / birth
  6. Blood transfusions / organ transplant
  7. Zoonoses ⇒ viral disease shared by animals and insects
72
Q

Viral Transmission

Factors

A
  • Stability of virus in the environment
  • Replication and secretion of virus into transmissible aerosols
  • Asymptomatic transmission
  • Transient or ineffective immune response to control reinfection or recurrence
73
Q

Risk Factors

A
  • Age
  • Health
  • Immune status
  • Occupation
  • Travel history
  • Lifestyle
  • Children in daycare
  • Sexual activity
74
Q

Critical Community Size

A

The minimum size of a closed population within which a human-to-human, non-zoonotic pathogen can persist indefinitely.

Depends on the # of seronegative, susceptible people.

75
Q

Geography and Season

Effects

A
  • Presence of cofactors / vectors
  • Habitat and season for arthropod vectors
  • School session
    • Close proximity and crowding
  • Home-heating season
    • Limited fresh air circulation
76
Q

Modes of Control

A
  • Quarantine
  • Elimination of the vector
  • Immunization
    • Natural infection
    • Vaccination
  • Treatment

Foundations of Disease (46 decks)

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