Iahi: 3.1 - Introduction To Virology

Front 1

What kind of parasites are viruses?

Back 1

Obligate intracellular parasites

Front 2

Why are viruses parasites?

Back 2

They rely on the metabolic machinery and protein biosynthetic machinery of the host cells

Front 3

How can the structure of a virus vary?

Back 3

- Naked vs. enveloped
- RNA vs. DNA genome

Front 4

What happens during the intracellular phase of a virus lifecycle?

Back 4

- Replication
- Transcription
- Synthesis of proteins
- Assembly of virions
(All within infected cells)

Front 5

What happens during the extracellular phase of a virus lifecycle?

Back 5

Particles must pass from cell to cell, throughout body, or between individuals

Front 6

What is the size range of viruses? Implications for type of microscope used?

Back 6

- Diameter from ~20 nM to ~300 nM
- Must be viewed with Electron Microscope

Front 7

What type of taxonomic method is used for virology? What does this mean?

Back 7

"Polythetic" - any given virus group is described using a collection of individual properties - a class whose members always have several properties in common although no single common attribute is present in all of its members

Front 8

Why is the taxonomic classification of viruses important?

Back 8

- Diagnosis
- Identification of new viruses
- Clarification of life cycle
- Drug design

Front 9

What are some possible properties that can be used for taxonomic classification of viruses?

Back 9

- Particle type
- Tissue tropism
- Disease etiology
- Serology
- Genome type

Front 10

How can viruses be classified based on particle type?

Back 10

- Icosahedral or Filamentous or Irregular
- Enveloped or Naked

Front 11

How can viruses be classified based on tissue tropism?

Back 11

- Skin
- Respiratory Tract
- Lymphoid Cells
- Etc.

Front 12

How can viruses be classified based on disease etiology?

Back 12

- Hepatitis
- Gastroenteritis
- Encephalitis
- Etc.

Front 13

How can viruses be classified based on serology?

Back 13

E.g., cross-reacting epitopes

Front 14

How can viruses be classified based on genome?

Back 14

- RNA: + sense vs. - sense, ds, segmented
- DNA: ss vs. ds, linear vs. circular

Front 15

What do +sense vs. -sense RNA viruses mean?

Back 15

+ sense --> same sense as mRNA
- sense --> needs to be copied to be inverse mRNA

Front 16

What forms the structure of a viral capsid?

Back 16

One or a few proteins that have repeating protein-protein contacts

Front 17

What kind of viruses can have capsids?

Back 17

- Naked viruses
- Enveloped viruses (matrix protein lies under envelope)

Front 18

What is the function of the capsid / envelope?

Back 18

- Packaging, protection, and delivery vehicle during transmission (designed to be stable until it contacts the next host)
- Exposed proteins are the targets of neutralizing antibodies

Front 19

What is the Baltimore classification scheme?

Back 19

- Classifies viruses based on genome type (DNA/RNA and ss/ds and +/- sense)
- I: ± ds DNA
- II: + ss DNA
- III: ± ds RNA
- IV: + ss RNA --> - ss RNA
- V: - ss RNA
- VI: + ss RNA --> - ss DNA

Front 20

What happens in Baltimore classification scheme I?

Back 20

- Start as ± ds DNA
- Transcribed to + mRNA
- Virus doesn't have to encode its own machinery because our cells have this transcription machinery (however viruses may also supply this for increased autonomy)

Front 21

What happens in Baltimore classification scheme II?

Back 21

- Start as + ss DNA
- Need to synthesize complement strand (- DNA) --> machinery is unique to / encoded by virus
- From there, - DNA is transcribed to + mRNA

Front 22

What happens in Baltimore classification scheme III?

Back 22

- Start as ± ds RNA
- Replicates using host machinery to + mRNA, but can also use some of its own machinery
- However there is never dsRNA in hosts, so the presence of it can activate interferon / immune system (need stealth mechanisms)

Front 23

What happens in Baltimore classification scheme IV?

Back 23

- Start as + ssRNA
- Converted to - ss RNA so that it is the correct sense for making + mRNA
- Also can be directly translated into proteins by host ribosomes

Front 24

What happens in Baltimore classification scheme V?

Back 24

- Start as - ssRNA
- Converted to + mRNA
- Also can be directly translated into proteins by host ribosomes

Front 25

What happens in Baltimore classification scheme VI?

Back 25

- Start as + ssRNA
- Reverse transcribed by proteins provided by the virus to - ssDNA
- -ssDNA is replicated to ± dsDNA
- Host machinery transcribes into + mRNA

Front 26

How does the size of RNA viruses compare to DNA viruses?

Back 26

- RNA viruses in general are smaller (7-27 kb)
- DNA viruses have a larger range and can be much larger (5-280 kb)
- Although the RNA viruses are usually smaller, the smallest virus is a DNA virus (parvo virus)

Front 27

What is the difference between a "virion" and a "virus"?

Back 27

- Virion is a viral particle (not all are infectious)
- Virus is an infectious particle

Front 28

What is MOI?

Back 28

Multiplicity of Infectino

Front 29

What is CPE?

Back 29

Cytopathic Effect

Front 30

What is Viremia?

Back 30

Spread of virus throughout the body via the bloodstream

Front 31

What are some ways to quantify an infectious virus?

Back 31

- Plaque Assay
- Focus Forming Assay
- Single-step Growth Curve

Front 32

What happens in a "Plaque Assay"?

Back 32

- Tissue culture assay for quantitating infectious virus
- Titration of the number of infectious progeny (unit = plaque forming unit, pfu)
- The plaque ("hole") reflects the zone of infection and spread initiated by a single infectious unit (pfu)

Front 33

What happens in a "Focus Assay"?

Back 33

For viruses that induce cell proliferation rather than cell death

Front 34

What happens in a "Single-Step Growth Curve"?

Back 34

Provides quantitation of "burst size"

Front 35

What do naked capsid virions contain?

Back 35

- DNA or RNA
- Structural proteins
- Enzymes and nucleic acid-binding proteins
(= Nucleocapsid)

Front 36

What is a Nucleocapsid?

Back 36

- DNA or RNA
- Structural proteins
- Enzymes and nucleic acid-binding proteins

Front 37

What do enveloped virions contain?

Back 37

- DNA or RNA
- Structural proteins (e.g., capsid), attachment and fusion proteins (for binding and entry), auxiliary proteins (aid in disassembly after entry)
- Enzymes and nucleic acid-binding proteins
(= Nucleocapsid)
+ Glycoproteins and membrane

Front 38

The membrane of a virion is derived from what?

Back 38

Nucleus, ER, Golgi, vesicles, plasma membranes

Front 39

How do viruses replicate?

Back 39

"Xeroxing" - make many copies at once

Front 40

What are the steps in a viral lifecycle?

Back 40

1. Attachment
2. Penetration
3. Uncoating
4. Synthesis of components (synthesis of viral mRNA, translation of viral proteins, genome replication)
5. Assembly of viral components
6. Exit/maturation

Front 41

How does a virus mediate attachment (step 1)?

Back 41

- For both naked and enveloped viruses, a viral surface protein recognizes a receptor on the target cell
- Cell surface receptors (proteins or carbohydrates) can often determine species or tissue tropism
- Antibodies that interfere with this interaction "neutralize" viral infectivity

Front 42

What is the virus recognition of its receptor important for?

Back 42

- Host range (human vs. other hosts)
- Cell tropism (location of infection in the body)

Front 43

What is the receptor for HIV?

Back 43

Human CD4 on T cells

Front 44

What is the receptor for Epstein-Barr Virus?

Back 44

Human Complement receptor CD21

Front 45

What is the receptor for Rhinovirus?

Back 45

Human ICAM-1

Front 46

What is the receptor for Influenza Virus?

Back 46

Sialic Acid

Front 47

How does a virus mediate entry (step 2)?

Back 47

- Naked virus enters the cell via endocytosis and is surrounded by endosomal membrane
- Some enveloped viruses use their glycoprotein to induce fusion of virus and cell membranes; fusion releases capsid into the cytoplasm, leaving traces of viral protein in the plasma membrane
- Some enveloped viruses are taken up by endocytsois and fusion of their membrane with the membrane of an acidic endosomal compartment releases the capsid into the cytoplasm

Front 48

How does a virus mediate genome replication and transcription (step 4)?

Back 48

- The replicative pathway a virus is reflected in, and depends upon, the enzymes it encodes
- Cells do not have enzymes that copy RNA --> RNA, or RNA --> DNA

Front 49

Where does viral replication and transcription take place?

Back 49

In the nucleus or in the cytoplasm, using cellular or viral enzymes

Front 50

What must all viruses synthesize to make proteins?

Back 50

+ sense mRNA

Front 51

What is used by viruses to synthesize viral proteins?

Back 51

All viruses use host ribosomes to synthesize viral proteins, although viral proteins may modify their translational specificity

Front 52

What is used by viruses to modify proteins?

Back 52

Host or viral machinery (e.g., phosphorylate)

Front 53

How do viruses affect the cellular membranes?

Back 53

Use, divert, or modify cellular membranes for replication and assembly

Front 54

How do viruses affect the host macromolecular synthesis?

Back 54

Many viruses "shut-off" host macromolecular synthesis; others manipulate the cell cycle of the host to provide the best replicative environment

Front 55

How does a virus mediate assembly (step 5)?

Back 55

- Proteins sorted to nuclear or cytoplasmic location
- Capsid proteins assemble
- Viral genome selectively encapsidated
- Viral membrane proteins synthesized (translation in ER), modified (glycosylated in Golgi), and trafficked to correct membrane (internal or plasma by vesicular transport)

Front 56

How does a virus mediate exit (step 6)?

Back 56

- Most enveloped viruses bud from the plasma membrane (also from nuclear membrane or into compartments of secretory pathway) and acquire the lipid envelope and viral membrane proteins
- Many naked viruses rely on cell lysis for release

Front 57

What kind of viruses can acquire a membrane in the cytoplasm?

Back 57

Poxvirus

Front 58

What are the possible outcome of infection at the cellular level?

Back 58

- Productive infection
- Latent infection
- Persistent infection
- Abortive infection

Front 59

What happens in a productive infection?

Back 59

Generally leads to cytopathic effect with a burst of virus production

Front 60

What happens in a latent infection?

Back 60

No production of infectious virus particles, but genetic information of the virus remains

Front 61

What happens in a persistent infection?

Back 61

Chronic virus production

Front 62

What happens in a abortive infection?

Back 62

Virus life cycle incomplete and virus lost

Front 63

How does a virus affect the host cell?

Back 63

Acute Cytopathic Effects:
- Membrane fusion of adjacent cells to form giant, multi-nucleate cells called syncytia
- Shuts off host metabolism
- Induces apoptosis
- Leads to cell death and necrosis
Cell transformation: loss of normal growth control, "oncogenic potential"
Or no apparent effect

Front 64

What factors influence the species/organ/tissue for disease by virus?

Back 64

- Tropism: receptor, tissue-specific cellular components required for infection, tissue-specific restriction factors that abort infection, temperature or pH or activating proteases
- Transmission: respiratory, fecal/oral, direct contact (sexually, or parenteral - blood), indirect (fomites or vectors)

Front 65

How do viruses cause disease?

Back 65

- Virus destruction of infected cells
- Viral modification of infected cell function
- Immune and inflammatory responses to viral infection (fever, rash, myalgia, immune-mediated damage or destruction of cells or tissues)
- Combination

Front 66

What are the components of the host defenses to viruses?

Back 66

- Innate response (soluble mediators and/or apoptosis)
- Adaptive response (humoral)
- Adaptive response (cell-mediated)
- Memory response (B and T cells)

Front 67

What soluble mediators (innate response) are part of the host defenses to viruses? How do they function?

Back 67

- Interferons (IFNs)
- Cytokines
- Chemokines
- Antiviral response within infected cell --> make surrounding cells resistant to infection --> recruit effector cells (NK cells and macrophages)

Front 68

How does apoptosis (innate response) play a part in the host defense to viruses?

Back 68

Programmed cell death to avoid release of infectious virus

Front 69

What are the components of the humoral adaptive response to viruses?

Back 69

- Neutralizing antibodies - block attachment or entry
- Complement fixing antibody - lyse virions or infected cells

Front 70

How does the cell-mediated adaptive response help the host defend against viruses?

Back 70

MHC presentation of viral peptides --> killing of virus-infected cells by cytotoxic T cells

Front 71

What are the targets for antiviral therapy?

Back 71

The basic steps in a viral life cycle
1. Attachment
2. Penetration
3. Uncoating
4. Synthesis of components
5. Assembly of viral compoennts
6. Exit / maturation