3.2 viruses as pathogens Flashcards

1
Q

what is tissue tropism? what influences it?

A

reflects the ability of a given pathogen to infect a specific organ or sets of organs

  • Tissue tropism is heavily influenced by the presence of cellular receptors permitting the entry of the virus
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2
Q

what explains species susceptibility to certain viruses?

A
  • Animal species express different receptors which explains species susceptibility to some viruses
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3
Q

what do viruses exploit to gain entry to a host cell?

A

-molecules on the surface of a host cell’s plasma membrane = receptors

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4
Q

what is the general molecular structure of a viral receptor?

A

can be proteins, glycoprotein, carbohydrate, or lipid

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5
Q

how does a virus attach to the membrane of a host cell? How does this work with influenza, for example?

A
  • Viral surface proteins/glycoproteins (ligands) interact with
    receptors/co-receptors on the surface of host cells
    *Viruses interact with the cellular receptor in a lock-and-key
    manner
  • Influenza hemagglutinin (LIGAND) interacts with sialic acid linked glycoproteins on host cells (RECEPTOR)
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6
Q

what determines the mechanism of virus entry into the host cell?

A

the nature of the receptor

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7
Q

what mechanisms of entry into the host cell might a virus use?

A

-Direct penetration where a viral protein forms a pore to release its genome

-Receptor mediated endocytosis of all non-enveloped viruses and some enveloped viruses

-Fusion between the viral protein of enveloped viruses and the cell membrane

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8
Q

what mediates virus-cell fusion? where does it occur and at what pH?

A
  • Virus-cell fusion is mediated by one or more surface glycoproteins of the mature virion envelope.
  • Fusion can occur at the cell surface at neutral pH or within an endosomal compartment at low pH.
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9
Q

how does a viral fusion protein normally exist? What happens when it gets triggered?

A
  • The fusion protein exist in a ‘native’ fusion-competent state, which is most often, but not always, metastable.
  • Following triggering (low pH, interaction with receptors, enzymatic cleavage by proteases), the fusion protein undergoes conformational changes allowing the fusion peptide (hydrophobic amino acids) to embed itself into the target membrane.
  • The viral fusion protein inserts into the host cell’s plasma membrane > pulls 2 membranes together
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10
Q

what does fusion create? Why is this important?

A
  • Fusion allows the creation of a fusion pore that allows viral nucleocapsids to be released into the cytoplasm
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11
Q

what property of the fusion protein is an important virulence factor?

A
  • Changes in the fusion protein that influence its cleavage is an important virulence factor (ability of the virus to cause disease)- e.g., influenza virus and new castle disease virus
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12
Q

Which of the following statements is CORRECT about virus entry into the cell?
a. Virus tropism is shaped by availability of cellular receptors for virus entry
b. Direct penetration can be used by some viruses to enter into the cell
c. Virus-cell fusion is commonly used by enveloped viruses
d. Cleavability of the fusion protein is an important virulence factor
e. All of the above

A

e. All of the above

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13
Q

what occurs in the uncoating stage of viral entry to a cell? Where does this occur for RNA and DNA viruses?

A

ØThe virus particle is metastable: stable enough to move from cell to cell but primed to undergo structural changes and disassemble.
ØUncoating occurs when viral genome and capsid proteins separate
ØNucleocapsid proteins are enzymatically digested or destabilized to release the nucleic acid/genome
ØRNA viruses uncoat in the cytoplasm with few exceptions ØDNA viruses uncoat in the nucleus with few exceptions

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14
Q

what does viral genome replication involve?

A

Genome replication involves transcription, translation of proteins and replication of the genome to produce progeny virus

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15
Q

where does a DNA virus replicate and what does it require?

A

DNA virus: replicates using the host cell DNA polymerase, and it is transcribed by the host cell RNA polymerase
-in the nucleus with few exceptions

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16
Q

where does an RNA virus replicate and what does it require to do so?

A
  • RNA virus: host cell does not have a mechanism to replicate the genomic RNA. Viruses encode RNA dependent RNA polymerase to replicate their RNA genome.
    -in the cytoplasm with few exceptions
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17
Q

what do viruses need to synthesize their proteins?

A

Viruses need cellular ribosomes to synthesize their proteins. Cellular ribosomes only read mRNA!

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18
Q

how do + and - sense RNA viruses differ in their requirements for protein synthesis?

A

Positive RNA viruses: their genome is ready to be processed by ribosomes, so it acts as its own mRNA

Negative RNA viruses: their genome is not readable by the ribosomes, so it must be first converted to positive sense RNA by RNA dependent RNA polymerase (RdRp) prior to translation. Negative sense RNA viruses must package RdRp within their virion so it can readily start replicating the genome.

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19
Q

Which of the following statements is NOT CORRECT about genome replication?
a. The viral genome is used for two purposes (1) synthesis of protein after making mRNA, and (2) a template to replicate a genome for the progeny virus
b. DNA viruses use cellular polymerases to replicate their genome
c. Viruses with positive sense RNA genome use cellular RNA polymerases to synthesize new genomes for packaging into the progeny virus
d. None of the above
e. All of the above

A

c. Viruses with positive sense RNA genome use cellular RNA polymerases to synthesize new genomes for packaging into the progeny virus

20
Q

Which of the following statements is CORRECT about synthesis of viral proteins?
a. RNA viruses synthesize their proteins in the cytoplasm
b. Viruses with negative sense RNA genome need to package their own RNA dependent RNA polymerase for immediate transcription of mRNA for protein synthesis
c. Most DNA viruses replicate in the nucleus and do not require ribosomes in the cytoplasm for protein synthesis
d. Negative sense RNA genome can be directly used by ribosomes to synthesize protein
e. A and B are correct

A

e. A and B are correct

21
Q

how does the assembly of new viral particles in the cell occur? When does it occur?

A
  • Newly synthesized proteins and genomic molecules are assembled into new virus particles.
  • Assembly takes place through protein-protein and protein- genome interactions
  • Assembly varies significantly between viruses
  • Assembly takes place as separate or concurrent step to release of progeny virus
22
Q

how are viral particles released from the cell? What is important to determine the mechanism?

A

Two ways:
1. Lysis of the cell: non-enveloped viruses
2. Budding off the cell surface – enveloped viruses

23
Q

The envelope of a virus is usually derived from what part of the infected cell?
A. nucleic acids
B. membrane structures
C. ribosomes
D. genome

A

B. membrane structures

24
Q

what are inclusion bodies? What do the represent?

A
  • Are nuclear or cytoplasmic aggregates of viral replication
    intermediates such as capsid proteins and nucleic acids
  • They typically represent sites of viral multiplication in a cell
  • Visible by light microscopy
25
Q

3 ways that virus genomes can change overtime

A

1.Mutations are changes (insertions or deletions) in the viral
genome that arise due to errors made by polymerases.
-RNA viruses generally have higher mutational rates than DNA viruses, because viral RNA polymerases lack the proofreading ability of DNA polymerases
e.g. Antigenic drift of Influenza virus

  1. Recombination is rearrangement of the genome within or
    between viruses
  2. Reassortments takes place when RNA viruses exchange
    their segmented genomes when co-infecting a cell
    - Leads to major antigenic variations
    e.g. Antigenic shift of Influenza virus
26
Q

what major effects can changes in the viral genome have, practically?

A

Changes in the virus genome contribute to pathogenicity and can affect disease control and prevention strategies

  • Increased or decreased virulence (ability of the virus to cause disease)
  • Changes in the viral genome can shift the antigen determinants on viral surfaces
  • Development of vaccine and antiviral drug escaping variants (mutations)
27
Q

what is the definition of viral pathogenesis?

A

Viral pathogenesis is defined as the mechanisms by which viruses cause disease

28
Q

what are the stages in the viral process?

A
  1. entry
  2. primary replication
  3. spread
  4. secondary replication
  5. secondary viremia
  6. reach target organs
29
Q

what are commonly sites of secondary viral replication? what are some common target organs?

A

secondary rep.-bone marrow, liver, spleen, vascular endothelium
target organs-resp tract, mucus membranes, skin, brain, salivary gland, kidney

30
Q

what are some different viral routes of infectoin?

A

-food and water
-arthropod
-dog biting
-anus
-urogenital
-sexual contact
-alimentary
respiratory

31
Q

what is the incubation period?

A

Asymptomatic period after infection and
before the appearance of clinical disease

32
Q

what are the diffferent types of virus infection, based on timeframes?

A

-acute, self-limited
-latent; acute infection becomes latent with recrudescence and shedding
-chronic; can have chronically high viral load in tissue that eventually leads to death, or have an acute infection that becomes chronic with recurrent shedding
-slow

33
Q

what is horizontal virus transmission? how can it occur?

A

horizontal transmission: direct contact, indirect contact, vectors
(air, water, fomites, mosquitos)
excretion of viruses: respiratory, oral, fecal, milk, skin, uro-genital tract

34
Q

what is vertical virus transmission?

A

vertical transmission: gametes, placenta, milk, egg

35
Q

what is the difference between vertical and horizontal virus transmission?

A

In horizontal transmission, viruses are transmitted among individuals of the same generation, while vertical transmission occurs from mothers to their offspring

36
Q

what are 5 main mechanisms of viral disease production?

A
  • Direct cell (tissue) damage – cell lysis and cytopathic effect – many types of viruses
  • Cell transformation – malignant cells e.g., Marek’s disease
  • Inflammatory response – cytokine storm or immunopathology
  • Predisposition to bacterial infection – a lot of viruses that cause enteric and respiratory diseases, e.g., parvovirus, calicivirus
  • Immunosuppression – viruses that infect and kill immune cells, e.g., retroviruses, canine distemper virus
37
Q

what is active immunization? how long does protection last? is there a memory response?

A

Active: vaccinate with a modified form of the pathogen or part of a pathogen to induce the recipient to make antibodies
- Long term protection
- Induce a memory response

38
Q

what is passive immunization? does it give long term protection and is there a memory response?

A

Passive: give the product of an immune response (antibodies or immune cells) to a recipient
- High titers of antibodies may occur in convalescent serum from donor animals that recovered from a viral infection
- Short term protection
- No memory response

39
Q

what is the basic principle of immunization ie. what steps occur inside the body?

A
  1. vaccine delivers vaccine antigen and adjuvant (containing danger signals)
  2. PRR on dendritic cell recognizes antigen. antigen peptide presented by MHC class II on dendritic cell
  3. activation and trafficking to draining lymph node
  4. MHC class II presents to CD4+ T cell, which helps activate cytotoxic T cells and B cells
    >B cell will connect with viral antigen via BCR, proliferate. Maturation of antibody response. Memory B cell proliferation, plasma cell differentiation and antibody production
    >CD8+ T cell differentiates into effectors and memory T cells
    >plasma cells are long lived in the bone marrow
40
Q

what are the features of a good vaccine?

A
  • Induces a strong and long-lasting immune
    response that protects against the pathogen
  • Safe: administration causes less disease or side effects
  • Low cost (<$1 according to the WHO)
  • Easy to administer and practical to store and transport
41
Q

types of viral vaccines (5)

A
  1. Live-attenuated: Virus attenuated by multiple passages in cell cultures, or in different animal species.
  2. Inactivated/killed: Chemical (formaldehyde) or heat inactivate the whole virus and adjuvants used to enhance immune response
  3. Recombinant subunit: Vaccine contains recombinantly synthesized and purified parts of the virus (epitopes) that best stimulate a protective response
  4. Recombinant vector-based: Vaccine contains bacteria, virus or plasmid vectors used to deliver a protective protein of a pathogenic virus.
  5. RNA vaccines: LIKELY THE BEST VACCINES
42
Q

what animal virus has been eradicated using vaccines? What features of the virus made this possible?

A

Rinderpest (cattle plague)
* First and only animal disease eradicated in 2011 (it does not infect humans) …it caused famines and millions of human death

Rinderpest Global eradication program:
- Ring vaccination strategy
- Science + Society efforts!
- Low mutation rates, little variation between strains
- Clinical signs were obvious: easy to find outbreaks
- No wildlife reservoirs

43
Q

what are the strategies and mechanisms of antiviral activity? what are the requirements? potential targets?

A

Any stages of viral replication can be a target for antiviral intervention

Requirements
* The targeted pathway is preferentially essential for virus replication - the antiviral agent is active against the virus while having low or “acceptable toxicity” to the host organism

Potential targets
* All virus-encoded enzymes or enzymatic (and non-enzymatic) processes critical to virus replication and not essential for host cell survival

44
Q

what happens if an antiviral does not completely block replication?

A

The antiviral agent must block virus replication completely - Partial inhibition leads to RESISTANCE

45
Q

when should an antiviral drug be administered in the disease course?

A

In therapeutic setting it should be administered immediately after infection or appearance of clinical signs - infections are short (~7 days) and hard to diagnose early

46
Q

examples of antivirals used in vet med. is this common?

A

Examples of antivirals based on mechanism of action

  1. Inhibitors of viral DNA polymerase - Herpesviruses
    -Nucleoside analogs (Acyclovir, Gancyclovir, Ribavirin)
    -Pyrophosphate analog (Foscarnet)
  2. Inhibitors of reverse transcriptase -retroviruses
    - Zidovudine (AZT)
  3. Neuraminidase inhibitor – Influenza virus
    - Oseltamivir – Tamiflu
  4. Ion channel blockers
    - Amantadine, rimantadine - Influenza A
  5. Interferons
  6. Protease inhibitors
    - Ritonavir - HIV protease inhibitor - Saquinavir
    - Indinavir

Antivirals are not commonly used in Vet Med
* Can be expensive and not cost effective for food animals
* Unsure whether they will really help animals