Molecular Virology

Question 1

What are the four different configurations of the viral genome?

Answer 1

• single-stranded RNA (ssRNA)
• double-stranded RNA (dsRNA)
• single-stranded DNA (ssDNA)
• double-stranded DNA (ddDNA)

Based on this, we can separate viruses into different families.

Question 2

Describe the structure of viral genomes.

Answer 2

• double-stranded genomes have complementary base pairing
• RNA genomes can be linear and segmented (ie. more than one RNA per capsid
• DNA genomes can be linear or circular

Genomes can encode information (genes) in a positive or negative sense, 5’-3’ or 3’-5’ respectively.

Question 3

How do viruses use the Central Dogma to replicate?

Answer 3

DNA VIRUSES:
They use DNA Polymerase to simply follow through the Central Dogma and express their proteins.

RNA VIRUSES:
If they have negative sense RNA, they depend on RNA Polymerase, which can simply read off other copies of the RNA genome, regardless of the sense of the strand (positive or negative). This transcribes a positive strand, which can be sent through the Central Dogma to create proteins.

Question 4

Give two examples of proteins that viruses can produce.

Answer 4

POLYMERASE:
Polymerase proteins are enzymes that are involved in the catalysis of nucleotides to nucleic acids.
Viruses with DNA genomes produce DNA polymerases, while viruses with RNA genomes produce RNA polymerases.
Polymerase proteins interact with nucleic acids in protein-nucleic acid interactions.

STRUCTURAL PROTEINS:
These are proteins that form the capsid into which nucleic acid is packed.
These proteins interact with one another in protein-protein interactions.

Question 5

How do viral proteins promote pathogenesis?

Answer 5

As ‘obligate cellular parasites’, viral and cellular proteins shape the intracellular environment to facilitate viral replication, or evasion of an immune response.
Commonly, changes to the intracellular environment that facilitates virus replication or evasion of an immune response lead to disease (pathogenesis).

Question 6

How can virus pathogenesis lead to cancer?

Answer 6

As cells divide, they go through the cell cycle. During the cell cycle, the cell produces factors that a virus might need. An example of this is the production of nucleotides that can be used by viral polymerases to make new viral genomes.
Some viruses produce proteins that ensure that the cell continuously goes through the cell cycle.

Cancer can be defined as an uncontrolled cell division. Thus, viruses can cause cancer by causing uncontrolled cell division that benefits their replication.

Question 7

Give some examples of some viruses that can cause cancer, and describe how this could happen.

Answer 7

• Human Papilloma viruses (HPVs)
• Hepatitis B virus (HBV)
• Hepatitis C virus (HCV)
• Human Immunodeficiency virus (HIV)

Human Papillomavirus (HPV) proteins E6 and E7 remove the 'brakes' of the cell cycle.
E6 can remove/degrade p53, an important factor that halts the cell cycle, so it allows the cell cycle to go on.
E7 binds to RB, preventing it from binding to E2F, once again allowing the cell cycle to go on.

Question 8

How can virus pathogenesis lead to immunodeficiency?

Answer 8

Viruses must evade immune responses. Some immune responses are mediated by specific cells of the immune system. these immune cells recognise and kill cells infected by a virus.

To evade this type of immune response, some viruses replicate in the immune system cells whose functions is to recognise and kill infected cells.
Replication in immune cells hides the virus from the immune cells and inhibits immune cell functions.

Inhibition of immune cell function allows other pathogens to replicate in virus-infected hosts and, thus, disease occurs.

Question 9

Describe how HIV cause immunodeficiency.

Answer 9

In an uninfected person, the thymus produced normal CD4 cells, some of which will die of apoptosis (natural occurrence, as it keeps all of the cells being replenished).
In an infected person, some of the CD4 cells made by the thymus will be infected, and these, in turn, will cause a number of different molecular pathways to be activated, all of which cause cell death.

Question 10

List some HIV-associated pathogens.

Answer 10

VIRUSES:

• Kaposki’s sarcoma hepesvirus (KSHV) - cancer-causing
• Herpes simplex virus (HSV)

BACTERIA:

• Mycobacterium tubercolosis
• Salmonella

FUNGUS:

• Candida
• Cryptococcus neoformans

PARASITE:

• Cryptosporidium
• Toxoplasma gondii

Mostly, hosts never really die of the HIV; it simply facilitates the entry of other pathogens which then kill the host.