Lecture 8: Virology

Question 1

Describe Charles Chamberland’s contributions towards microbiology

Answer 1

1) Charles Chamberland (1851-1908) worked with Louis Pasteur, he developed Chamberland’s Porcelain Bacterial Filter which filtered out most microbes (bacteria, some viruses).
2) Marketed it as a water filter.

Question 2

List the properties of viruses (6)

Answer 2

1) Viruses are filterable agents; small size allows them to pass through filters designed to retain bacteria
2) Viruses are obligate intracellular parasites
3) Viruses cannot make energy or proteins independently of a host cell
4) Viral genomes may be RNA or DNA but not both
5) Viruses have a naked capsid or an envelope morphology
6) Viral components are assembled and do not replicate by division

Question 3

In order to be a successful pathogen, what 5 things must be true about the virus?

Answer 3

1) Viruses are not living
2) Viruses must be infectious to endure in nature
3) Viruses must be able to use host cell process to produce their components
4) Viruses must encode any required processes not provided by the host cell
5) Viral components must self-assemble

Question 4

1) How big are viruses?
2) Are viruses diverse?
3) What does a complete virus particle or virion consist of?

Answer 4

1) Viruses range in size from about 10 to 400 nm in diameter (big range)
2) Very diverse
3) A complete virus particle or virion consists of one or more molecules of DNA or RNA enclosed in a coat of protein. The virion is the entire viral particle

Question 5

Name 3 structures that can be found in viruses

Answer 5

1) Nucleocapsid core
2) Capsid
3) Envelope (some viruses)

Question 6

Define in terms of viruses:
1) Nucleocapsid core
2) Capsid

Answer 6

1) Viral nucleic acid (DNA or RNA) that is held within a protein coat called a capsid
2) The protein coat that surrounds the viral nucleic acid genome

Question 7

Define in terms of viruses:
1) Enveloped virus
2) Naked virus

Answer 7

1) Enveloped: The viral nucleocapsid is surrounded by an additional layer that can be very complex containing carbohydrates, lipids, and additional protein.
2) Naked virus: Viruses lacking an envelope

Question 8

The three types of viral capsid architecture are based upon what?

Answer 8

The symmetry of the capsid/ nucleocapsid

Question 9

Name and describe the three types of viral capsid architecture

Answer 9

1) Icosahedral: usually naked viruses, a few are enveloped
2) Helical: can be naked or enveloped
3) Complex: A complex structure that is neither of the above

Question 10

What are the 3 functions of the capsid?

Answer 10

1) Packages the genome/provides structural support
2) Protects the genome from nucleases (in serum) and adverse environmental conditions
3) Participates in attachment and entry of host cells

Question 11

1) Icosahedral capsids are made up of what?
2) What is the smallest repeating structural unit visible by electron microscopy that makes up the icosahedral nucleocapsid?

Answer 11

1) The capsids are constructed from ring or knob-shaped units called capsomers
2) A capsomer

Question 12

1) In terms of viruses, what are capsomers made up on?
2) What are capsomers made of?

Answer 12

1) Capsomers are made up on one or more viral structure (or capsid) proteins
2) Each capsomer is usually made of five or six protomers

Question 13

1) What groups of viruses have envelopes?
2) What do virus envelopes usually arise from?
3) What usually codes for viral envelope proteins?

Answer 13

1) Many animal viruses, some plant viruses, and at least one bacterial virus have an envelope.
2) Virus envelopes usually arise from host cell nuclear or plasma membranes;
their lipids and carbohydrates are normal host constituents
3) Viral envelope proteins are coded for by virus genes

Question 14

1) What are projected proteins in viruses and what are they called?
2) What do many projected proteins act as? What do the rest do?

Answer 14

1) Viral envelope proteins may project from the envelope surface
Projected proteins are called spikes. 2) Many act as VAPs: Viral Attachment Proteins. Some are enzymes (e.g. neuraminidase, polymerases).

Question 15

1) Name the 2 protein spikes found on the surface of the influenza virion
2) How many pieces of RNA or DNA does it have?
3) What species can be infected by influenza, and what changes about influenza when it changes species?

Answer 15

1) Hemagglutinin (HA) spike and neuraminidase spike
2) Very few genes; only 8 pieces of RNA that encode for all the proteins it needs.
3) Goes through pigs, birds, and humans.
Temperature changes and amino acid changes occur as the virus makes its way through different species.

Question 16

1) What can the viral factors of influenza do?
2) What are the host factors (vulnerability factors) for influenza infection?

Answer 16

1) Has viral factors (based on its genotype) that can block interferons from helping the immune system, aid in replication, and HA spike determines receptor binding.
2) Host factors: Underlying health issues, elderly age, etc.

Question 17

List the component, properties, and consequences (5) of the naked capsid viral structure

Answer 17

1) Component: Protein
2) Properties: Is environmentally stable to temperature, acid, proteases, detergents, and drying; is released from cells by lysis
3) Consequences:
1) Can be spread easily
2) Can dry out and still retain infectivity
3) Can survive the adverse conditions of the gut
4) Can be resistant to detergents and poor sewage treatment
5) Antibody many be sufficient for immunoprotection

Question 18

List the components (3), properties, and consequences (5) of the enveloped capsid viral structure

Answer 18

1) Components:
a) Membrane
b) Lipids
c) Proteins and glycoproteins
2) Properties: Is environmentally labile and is disrupted by acid, detergents, drying, and heat; modifies cell membrane during replication and is released by budding and cell lysis.
3) Consequences:
a) Must stay wet
b) Cannot survive the gastrointestinal tract
c) Spreads in large droplets, secretions, organ transplants and blood transfusions
d) Does not need to kill the cell to spread
e) May need antibody and cell-mediated immune response for protection and control

Question 19

Are naked or enveloped viruses more resistant to drying out?

Answer 19

Naked viruses

Question 20

1) What two types of genome can viruses contain?
2) What are the two types of DNA or RNA genome a virus can have?

Answer 20

1) Viruses can contain a DNA or RNA genome
2) The DNA or RNA genome can be single (ss) or double stranded (ds)

Question 21

1) How does the Baltimore classification system classify viruses? (what is it based on?)
2) What two things are true of all viruses?

Answer 21

1) Sorts viruses based on their genome
2) a) Eventually need to get to mRNA to create proteins.
b) Have the ability to replicate their genome

Question 22

List the 5 generalized steps of the viral life cycle

Answer 22

1) Adsorption: Host cell recognition and attachment of virus
2) Entry: of viral nucleocapsid or nucleic acid
3) Synthesis: of viral proteins and nucleic acids (eclipse phase)
4) Self-assembly: of virions
5) Release: of progeny virions

Question 23

Each cell can produce _______ particles (viruses) but only ______ of those are infectious due to the high mutation rate because of self-assembly.

Answer 23

100,000; 1-10%

Question 24

Describe the ‘attachment’ phase of the viral life cycle:
1) What is it mediated by?
2) What is usually its cell surface receptor?
3) What is it the determinant of?
4) What has the ability to block this interaction?
5) What do cell surface receptors normally do when not attached to a virus?

Answer 24

1) Mediated by viral envelope/capsid protein (called a viral attachment protein or VAP) that binds to a target cell receptor molecule.
2) Cell surface receptor is usually a specific cell surface glycoprotein or a carbohydrate moiety attached to a lipid.
3) Determinant of cell/tissue tropism (which cells it can infect).
4) Interaction can be blocked by a neutralizing antibody; the attachment step is major target for the immune system.
5) Cell surface viral receptors have important functions in normal host cellular metabolism.

Question 25

Give an example of attachment using influenza

Answer 25

Influenza’s hemaglutinin attachment protein recognizes target vertebrate cells and initiates fusion between host and viral membranes, determines how well it can infect.

Question 26

Describe the ‘entry’ phase of the viral ‘life’ cycle in enveloped viruses:
1) What two ways can they use to enter the host cell?
2) What mediates their fusion?
3) When is the viral envelope removed?
4) What is the fusion process dependent on?

Answer 26

1) Enveloped viruses can enter by fusion of viral envelope with a cellular membrane or by endocytosis
2) Fusion is mediated by a viral “fusion” protein
3) Viral envelope is removed when fusion occurs and the viral nucleocapsid is ‘ejected’ into the host cell’s cytoplasm
4) Fusion process is pH dependent; cell surface at neutral pH vs fusion occurs in an endosome at an acidic pH

Question 27

Describe the ‘entry’ phase of the viral ‘life’ cycle in naked viruses:
1) How do they enter the host cell?
2) What is released after entry? What is extruded?

Answer 27

1) Naked viruses enter by receptor mediated endocytosis
2) After entry, the viral nucleocapsid is released into host cell cytoplasm and uncoated, or the viral genome is extruded into host cell cytoplasm through the endosome or plasma membrane (viropexis)

Question 28

Describe the ‘uncoating’ phase of the viral ‘life’ cycle:
1) What is stripped away from the viral nucleic acid?
2) Where does the viral genome travel after it’s uncoated?

Answer 28

1) Nucleocapsid proteins are partially or completely stripped away from the viral nucleic acid
2) Uncoated viral genome travels to site of genome replication

Question 29

1) Where do DNA viruses usually replicate?
2) Where do RNA viruses usually replicate?

Answer 29

1) DNA viruses usually replicate in the nucleus of a host cell
2) RNA viruses usually replicate in the cytoplasm of a host cell

Question 30

1) Define the ‘replication’ phase of the viral ‘life’ cycle
2) What 3 things occur during this phase?

Answer 30

1) Defined as the production of viral components
2)
a.Genome replication
b. Production of viral mRNAs
c. Production of viral proteins

Question 31

What two things are produced during the ‘replication’ phase of the viral ‘life’ cycle?

Answer 31

1) Viral mRNAs
2) Viral proteins

Question 32

1) Define the ‘assembly’ phase of the viral ‘life’ cycle
2) Where are DNA viruses usually assembled?
3) Where are RNA viruses usually assembled?
4) What directs the genome to new capsids?
5) How do the viral proteins assemble?

Answer 32

1) The assembly and maturation of new virions
2) DNA viruses are usually assembled in the host cell nucleus
3) RNA viruses are usually assembled in the host cell cytoplasm
4) The viral genome contains “packaging signals” that direct it to new capsids
5) The viral proteins “spontaneously” assemble at the correct site in the cell (along with the nucleic acid genome)

Question 33

1) Define the ‘release’ phase of the viral ‘life’ cycle
2) How are enveloped viruses released? When do they pick up their membrane?
3) How are non-enveloped viruses usually released?

Answer 33

1) The release of new virions
2) Enveloped viruses are released by budding through the appropriate cell membrane
Viruses pick up their membrane during the process of budding
3) Non-enveloped viruses are usually released by lysis of the host cell

Question 34

1) Where are DNA viruses replicated? Where are they assembled?
2) Where are RNA viruses replicated? Where are they assembled?

Answer 34

1) DNA viruses are usually both replicated and assembled in the host nucleus
2) RNA viruses are usually both replicated and assembled in the host cytoplasm

Question 35

Describe replication in the Herpes Simplex Virus Type I

Answer 35

Rolling circle replication creates a byproduct called concentric DNA, which is where multiple copies of that DNA are readily available in the nucleus

Question 36

There are 3 possible outcomes of a viral infection of a cell (viral pathogenesis); what are they?

Answer 36

1) Abortive infection: Failed infection; virus was unsuccessful.
2) Lytic infection: Ends in cell death
3) Persistent infection: Infection without cell death

Question 36

What are the 3 types of persistent infections? Describe them

Answer 36

1) Senescence: Viruses are produced and the cell stops dividing but is still alive. A type of persistent infection.
2) Latent: Virus production may stop and start, has no effect on the cell. A type of persistent infection.
3) Transforming (of a host cell; the integration of viral DNA in the cell): DNA viruses are not produced, RNA viruses are produced. Causes immortalization (cancer). A type of persistent infection.

Question 37

What type of viral infection results in a cell becoming cancerous?

Answer 37

Transforming infections (a type of persistent infection)

Question 38

Define cytocidal infection and cytopathic effects

Answer 38

1) Cytocidal infection: an infection that results in cell death
2) Cytopathic effects: microscopic or macroscopic degenerative changes or abnormalities in host cells and tissues

Question 39

List the 8 possible mechanisms for host cell damage (by viral pathogens)

Answer 39

1) Inhibition of host DNA, RNA, and protein synthesis
2) Damage of cell endosomes; results in release of hydrolytic enzymes
3) Alteration of plasma membranes by insertion of viral proteins; infected cells are attacked by host immune system
4) High concentrentration of viral proteins can have direct toxic effect on cells and organisms
5) Formation of large intracellular structures called inclusion bodies (often composed of subunits of viral proteins or host cell components) which disrupt cell structure
6) Chromosomal disruptions
7) Host cell is not destroyed, but is transformed into a malignant cell
8) Cell fusion: expression of viral envelope/ fusion proteins on the surface of an infected cell. Can cause it to fuse with nearby, uninfected cells. Fused cells usually die and are called syncytia or multinucleated giant cells.

Question 40

What are the 8 steps of the viral disease process (viral pathogenesis)?

Answer 40

1) Transmission
2) Entry into host
3) Primary viral replication
4) Viral local/ systemic spread
5) Secondary viral replication/ cell tropism
6) Cell damage/ disease production
7) Shedding of virus
8) Host death/ recovery

Question 41

What are the 3 primary modes of transmission of viruses?

Answer 41

1) Direct transmission (horizontal and vertical transmission)
2) Animal to human transmission
3) Transmission by arthropod vector

Question 42

Define horizontal and vertical transmission of viruses

Answer 42

1) Horizontal transmission: from person to person
2) Vertical transmission: from mother to child (perinatal and natal)

Question 43

What are the most common ways viruses are transmitted?

Answer 43

Inhalation and inoculation of virus into mucosa on contaminated hands/ objects are the most common ways viruses are transmitted

Question 44

1) Where do viruses enter their host cell?
2) What are the two main barriers for entry of viruses?

Answer 44

1) Portal of entry
2) Mechanical/ physical barriers and adaptive barriers (the immune response)

Question 45

Differentiate between:
1) Primary replication
2) Primary replication + secondary infection

Answer 45

1)The production of disease at a virus’s portal of entry (short incubation times)
2) Cells at the portal are infected, virions are produced, and systemically spread to a second site. Requires longer incubation times.

Question 46

What mechanisms of spread can be used by viruses in secondary infection? (3)

Answer 46

1) Bloodstream (viremia)
2) Lymphatics
3) Neuronal spread: uses neurons as conduits.

Question 47

What are the 3 types of tissue tropism?

Answer 47

Specific tissue, cell tropism, specific cell type

Question 48

What two barriers in the human body are highly effective in keeping viruses out?

Answer 48

1) Blood-brain barrier
2) Placental barrier

Question 49

Define direct and indirect tissue damage

Answer 49

1) Direct tissue damage: damage that occurs by replicating in, and killing or transforming host cells
2) Indirect tissue damage: the immune response to viral infection causes cell/ tissue damage (symptoms)

Question 50

1) Where are viruses typically shed?
2) When are those infected with a virus most contagious?

Answer 50

1) Usually the virus is shed from the same body surfaces at which it enters
2) During active shedding

Question 51

What influences whether or not a host lives or dies from a viral infection?

Answer 51

Just like with bacteria, all of the following play a role:
1) Strains
2) Type of virus
3) Host genetics and immune system

Question 52

Differentiate between apparent and inapparent viral infections. Which is more common?

Answer 52

1) Inapparent infections: subclinical or asymptomatic infection
a) Virus replicates in the host, but no clinical symptoms develop
Most common type of infection
2) Apparent infection: symptomatic infections; can either be acute or persistent

Question 53

1) What are the two types of apparent viral infection?
2) What are the two types of persistent viral infection?

Answer 53

1) Acute and persistent
2) Chronic and latent

Question 54

Differentiate between acute and persistent viral infections

Answer 54

1) Acute infections:
Overall rapid onset and last for a short period of time (days to weeks; ex: influenza)
2. Persistent infections: Lasting many years; can be chronic or latent

Question 55

Differentiate between chronic and latent viral infections. Give examples of each.

Answer 55

1) Chronic virus infections; virus is almost always detectable, but clinical symptoms may be either mild or absent for long periods
a) Examples: Hepatitis B virus and HIV
2) Latent virus infections; virus stops reproducing and remains dormant for a period before activating again.
During latency there are no symptoms (viruses are hidden or less potent)
a) Examples: Herpes simplex virus, Varicella-zoster virus, Epstein-Barr virus

Question 56

What causes latency in viral infections? (4 steps)

Answer 56

1) Viral genome was incorporated into the chromosome (provirus or phage).
2) Virus becomes less antigenic (less susceptible to immune attack).
3) The virus hides in an area that can’t be reached by the immune system (ex: nervous system).
4) Then the virus mutates to the less virulent form, which slows production.

Question 57

List the 8 different ways viruses evade host antiviral immune defenses

Answer 57

1) Overwhelming the host quickly
2) Production of large quantities of virus and/or viral antigens
3) Shedding of virus from site of primary infection
4) Infection of cells of the immune system
5) Production of “Anti-Immune” Substances (Molecular Bombs)
6) By replication in immune privileged sites (ex: eye or CNS)
7) Establishment of latent infection.
8) By undergoing antigenic variation (alteration of viral antigens); the emergence of new variants.

Question 58

Overwhelming the host quickly is characteristic of what viruses?

Answer 58

Characteristic of acutely lethal viruses (e.g. Ebola)

Question 59

1) Why does producing large quantities of the virus or viral antigens work against the host immune system?
2) Why does shedding the virus from the primary site of infection work against the host immune system?

Answer 59

1) The immune system can’t keep up
2) The immune response has not developed

Question 60

What are the 4 types of anti-immune substances (molecular bombs) that can be made by viruses?

Answer 60

1. Virokines: virally encoded cytokine analogues
2. Viroreceptors: virally encoded cytokine receptor analogues
3. Inhibitors of MHC class I antigen presentation
4. Inhibitors of the Interferon response

Question 61

Differentiate between virokines and viroreceptors

Answer 61

1. Virokines: virally encoded cytokine analogues
2. Viroreceptors: virally encoded cytokine receptor analogues

Question 62

What are the two types of viral antigenic variaiton? Describe them.

Answer 62

1) Antigenic drift: accumulation of point mutation in viral gene(s) changes their antigenicity.
2) Antigenic shift: exchange of genome segments between two different serotypes of virus infecting the same cells results in production of viral progeny which contain genes/antigens from both parental virus strains. Can result in the emergence of new pathogens.

Question 63

Differentiate between antigenic drift and antigenic shift

Answer 63

1) Antigenic drift: accumulation of point mutation in viral gene(s) changes their antigenicity.
2) Antigenic shift: exchange of genome segments between two different serotypes of virus infecting the same cells results in production of viral progeny which contain genes/antigens from both parental virus strains. Can result in the emergence of new pathogens.

Question 64

What mediates the innate immune response to viral infection?

Answer 64

Interferons

Question 65

Describe how DAIs (double-stranded RNA-activated inhibitor) work (3 steps)

Answer 65

1) A part of our innate immune system that’s normally inactive, until it sees a virus with double-stranded RNA.
2 )Then DAI phosphorylates and becomes active, and recruits initiation factor II and activates it.
3) Then it deactivates initiation factor II by phosphorylating it, which slows down synthesis of viral proteins and gives the cell more time to kill the virus (or kill itself).

Question 66

How do viruses combat DAIs of the innate immune system?

Answer 66

Some viruses have extra genetic material called ‘small RNAs’ that they bring with them in their capsules; these small RNAs have the ability to bind to and lock DAI in an inactive state (so it can’t phosphorylate to activate)

Question 67

List the 3 primary bacterial evasion strategies and how viruses respond to them

Answer 67

1) Receptor issues: The bacteria changes the receptor to prevent the virus from binding. The virus in turn learns how to bind to the new receptor.
2) Running interference: Bacteria put tons of sugars on their surface, preventing the virus from reaching the host cell surface. Viruses then begin to carry enzymes that break down sugars.
3) New coat: The bacteria modify their sugars and create variations in them so the viruses can no longer interact with the sugar coat.

Question 68

How do you cultivate viruses?

Answer 68

1) Create a lawn of bacteria on a plate
2) Add virus to the bacterial lawn
3) The virus begins to form plaques and lyse bacterial cells

Question 69

1) Define viroids.
2) How do viroids replicate?
3) What do viroids infect?
4) What are the two families of viroids?

Answer 69

1) Viroids are unencapsulated nucleic acids that consist of only RNA
2) Despite their small size and limited genetic info, they replicate autonomously (rolling circle replication)
3) Cause diseases in higher plants
4) One replicates in nucleus, other in chloroplasts

Question 70

1) How do viroids move?
2) How old are viroids?
3) How do viroids act as pathogens?

Answer 70

1) Move intracellularly, accessing neighboring cells through plasmodesmata
2) They’re ‘molecular fossils’ and predate the current world of DNA and protein (supports RNA World Hypothesis).
3) They don’t encode proteins, they act through a method called RNA silencing (binds and stops things from happening in host cell)

Question 71

1) Define prions
2) What are the two forms prions exist in?
3) What happens if the two prion types interact?
4) How do prions act as pathogens?

Answer 71

1) Proteinaceous infectious particles that cause neurodegenerative disease
2) Abnormally folded form and normal cellular form
3) Interaction between the two prion types usually causes the normal form to turn into the abnormal form.
4) Crosslinking of normal protein > triggers apoptosis > neuron loss