Viruses

Question 1

Explain the global impact of viral disease.

Answer 1

In the past, the baseline for morbidity from vaccine preventable viral diseases was up to one hundred percent higher than currently in developed countries. Some of the diseases that have been almost eradicated are smallpox, measles, polio and rubella.

Morbidity from a viral disease for which there was no vaccine until recently (Rotavirus):
Rotavirus caused 440,000 deaths each year, 82% of which are in low income countries where the risk of dying due to rotavirus before 5yo was 1 in 205.

Many viruses still have no vaccine such as HIV/AIDS:

HIV/AIDS is largely distributed across eastern Asia and the pacific as well as sub-Saharan Africa however there are no regions across the globe unaffected by this virus.

Question 2

What is a virus?

Answer 2

Viruses are subcellular genetic elements and obligate parasites. They aren’t cells and cannot replicate on their own, nor are they motile as they do not have their own energy supply. There is a large diversity in the size and morphology of viruses.

Question 3

How are viruses classified?

Answer 3

Viruses are classified into families by the following categories. All families names end with ‘viridae’.
- kind of nucleic acid genome
- strategy of replication (how the mRNA is produced from the genome)
- morphology of the virion
Genera, species and types are distinguished by different arrangements of genes, sizes of proteins, serological reactions and often on the type of disease caused by the virus.

Viruses can also be grouped based on epidemiologic/pathogenic criteria

Question 4

List some of the methods of detection of viruses.

Answer 4

Viruses can be detected via:
- direct visualisation on EM
- viral cultivation which can often be slow but will give better treatment plans
- viral protein/antigen detection*
- host serological response*
- viral gene detection*
None of these methods distinctly imply causality, and those marked with * can only detect that which is being tested for.

Question 5

What are the particles of the virus called?

Answer 5

Virions

Question 6

Explain the component of the virus? Genome

Answer 6

can be either DNA or RNA

Question 7

Explain the component of the virus? Capsid

Answer 7

protective protein shell surrounding the genome and forming the core of the viral particle. Clusters of capsid protein subunits (if visible) are called capsomers.

Capsid Symmetry:
To protect the genome from breakdown by nucleases, the capsid proteins are assembled symmetrically around the nucleic acid to form either an icosahedral capsid or a helical capsid.

Question 8

Explain the component of the virus? Nucleocapsid

Answer 8

Capsid most closely associated with the viral nucleic acid.

Question 9

Explain the component of the virus? Envelope

Answer 9

lipid membrane surrounding either the nucleocapsid or capsid which is derived from host cell membrane. It contains virus-encoded glycoproteins.

Question 10

Explain the component of the virus? Matrix

Answer 10

some viruses have a protein later connecting the capsid and envelope glycoproteins

Question 11

Explain the size of viruses relative to other cells?

Answer 11

Viruses are very small, much smaller than bacteria and human cells, however, despite their small size (too small to be seen by LM), very detailed information has been gathered by bombarding the viral particles with electrons and x-rays.

Question 12

What are Enteric Viruses?

Answer 12

• replicate primarily in and are localised to the intestinal tract
• acquired by ingestion of material contaminated by faeces
• rotavirus, calicivirus, some adenoviruses

Question 13

What are some Respiratory Viruses?

Answer 13

• viruses of the respiratory tract, often acquired by inhalation of droplets
• phinoviruses, some adenoviruses

Question 14

What are Arboviruses?

Answer 14

• viruses that infect insects that ingest vertebrate blood, replicate in the insect and are passed on by bite

Question 15

What are some Sexually Transmitted viruses?

Answer 15

-Herpes viruses, papilomaviruses as well as some retroviruses and hepatitis viruses.

Question 16

Explain Hepatitis Viruses?

Answer 16

The principle target of these viruses is the liver.
Hep A & E: spread via enteric route
HEP B, C, D: spread by blood/sexually

Question 17

What are some basic steps of viral replication?

Answer 17

1. Attachment
2. Penetration
3. Uncoating
4. Genome Replication
5. RNA synthesis
6. Protein Synthesis
7. Assembly
8. Release

Question 18

What is the mechanism for attachment/adsortption in viral replication?

Answer 18

1. Attachment/Adsorption
   Viral attachment protein binds specifically to a receptor on the cell plasma membrane. This interaction defines and m]limits the host species as well as the type of cell that is infected.
   Receptors may be:
   
   • protein (ICAM-1 for most rhinoviruses)
   • carbohydrate (sialic acid for influenza virus)
     Receptors molecules are not on a cell for the benefit of the virus but are involved in normal cell processes

Some viruses use two different receptors on the same host cell, for initial attachment and then closer attachment.

Question 19

What is the mechanism for penetration in viral replication?

Answer 19

2. Penetration: two ways into a cell
   - After adsorption, the coat of enveloped viruses may fuse with the host cell membrane and release the virus nucleocapsid directly into the cytoplasm.
   - Other viruses (enveloped and non-enveloped) enter the cell by a process of ‘endocytosis’ which involves invagination of the cell membrane to form vesicles in the cell cytoplasm.

HIV is an example of a virus whose contents is directly released into the cytoplasm.
- The hydrophobic fusion region of gp41, once exposed, can initiate fusion of the membranes

Question 20

What is the mechanism for uncoating in viral replication?

Answer 20

3. Uncoating
   - Refers to the release of the viral genome from its protective capsid to enable the nucleic acid to be transported within the cell and transcribed to form new progeny virions.

• Togavirus is an example of a virus that enters the cell by the endocytic route.
  In some cases, release from the endosome is triggered by the low pH of these vesicles which induces a conformational change in the viral proteins that exposes a fusion region. In other cases lysis of the endosome occurs to release the virus.

Question 21

What is the mechanism for Amplification in viral replication?

Answer 21

4. Amplification of the viral genome and viral proteins
   - Nucleic acid replication produces new viral genomes for incorporation into progeny virions.
   - In general, DNA viruses replicate mainly in the nucleus and RNA viruses mainly in the cytoplasm. (Exceptions are influenza virus and poxvirus.)
   - Messenger RNA (mRNA) is produced and codes for viral proteins that are translated by the host cell.
   - “ Early” proteins are usually non-structural (eg. DNA or RNA polymerases) and late proteins are structural, eg. capsid proteins, ie. building blocks of the virion.

Question 22

Explain Translation and Protein Processing.

Answer 22

Translation and Protein Processing:

• Translation of structural and non-structural proteins is carried out by ribosomes in the host cell cytoplasm.
• Post-translational cleavage of polyproteins or trimming of structural proteins usually needs virus-coded proteases.
• Glycosylation of envelope glycoproteins occurs in RER and Golgi vesicles which results in them being deposited on the cell surface.

Question 23

What is the mechanism for assembly and release in viral replication?

Answer 23

5. Assembly & 6. Release
   Non-enveloped animal viruses:
   - All have an icosahedral structure. There are many different strategies for assembly of such structures.
   - One simple strategy is the spontaneous assembly of the capsid proteins around the nucleic acid genome.
   - The virus particle may require proteolytic cleavage to induce the final conformation in the capsid proteins of the mature infectious virion.
   - Virions accumulate in the cytoplasm or nucleus and are only released when the cell eventually lyses.

Enveloped viruses:

• Most release may take place by budding from the cell surface. (influenza virus, measles virus)
• Patches of viral envelope glycoproteins accumulate in the plasma membrane.
• Capsid proteins and nucleic acid condense directly adjacent to the cell membrane
• The membrane surrounding the nucleocapsid then bulges out and becomes “nipped off” to form the new enveloped virion.
• Some utilize the cellular secretory pathway to exit the cell. Virus particles enclosed within Golgi-derived vesicles are released to the outside of the cell when the transport vesicle fuses with the cell membrane. (Coronavirus)

Question 24

What are inclusion bodies?

Answer 24

Inclusion Bodies:

Inclusions represent accumulated viral proteins at the site of virus assembly

Question 25

Explain the mechanism of cell transformation

Answer 25

Cell Transformation:
Some viruses encode oncogenes whose expression in the virus infected-cell is associated with tumour production. These genes, originally acquired from the host cell itself, were picked up during integration of the virus genome into the host DNA, way back in evolution.

Most oncogenes code for proteins with growth promoting properties and their expression can lead to uncontrolled proliferation of the infected cell and tumour development. Other viruses cause tumours because their replication affects the cellular version of an oncogene.

Question 26

Give a general overview of viral genetics and evolution.

Answer 26

Viral Genetics and Evolution:
Viral genomes are continually changing as a result of:
- mutation (errors in copying the nucleic acid, esp. RNA viruses - can exist as quasispecies eg. HCV)

…or, if two viruses infect the same cell:

- recombination (exchange of stretches of nucleic acid between genomes of 	similar sequence - esp. DNA viruses) 
- reassortment (swapping of segments for viruses that have segmented 	genomes)  

These changes may be either lethal to the virus, disadvantageous, neutral or give the virus a selective advantage (eg. increased growth rate, immune escape)

Question 27

What are some ways the infectious process of viruses can be stopped?

Answer 27

The infectious process can be halted by:

• antibody that blocks uptake and/or neutralises progeny virus
• killing the infected cell by cytotoxic T cells, NK cells or Ab-mediated mechanisms
• interferon
• blocking the replication cycle by specific antiviral drugs

Question 28

What are Nucleoside Analogs? What are they used for? Give an example.

Answer 28

Nucleoside Analogs:
- Acyclovir for Herpesvirus infections
DNA is a polymer of nucleotides:
- Nucleosides have no phosphate groups - Nucleoside triphosphate is the substrate for the DNA polymerisation
- The mono, di and triphosphate forms of the nucleosides are called nucleotides.

Acyclovir is a nucleoside analogue:

• Acyclovir is a guanosine analogue.
• Phosphate groups can be added so that the analogue can be incorporated into DNA
• But the 3’ hydroxyl group required to extend the DNA polymer is absent.