L36_Viral Genetics

Question 1

Order the following viruses from largest to smallest genome: Parvovirus, Adenovirus, Papillomavirus, Retrovirus, pox virus, herpes virus

Answer 1

Parvovirus (2), Retro virus (3), Papillomavirus (8), Adenovirus (10), Herpes Virus (70), Pox Virus (up to 200)

Question 2

Are virus genes prokaryotic or eukaryotic?

Answer 2

Eukaryotic

Question 3

how does the virus genome determine the cell tropism of the virus?

Answer 3

Each virus promoter binds specific transcription factors. If these factors are not present in a cell the virus will not survive. e.g. papillomavirus gene expression is regulated by keratinocyte factors, thus it is skin specific.

Question 4

Describe some strategies viruses use to have an extremely efficient genome.

Answer 4

No wasted space
overlapping reading frames
translational frame shifts
Alternative Splicing
Polyproteins

Question 5

Are viral polyproteins cleaved by viral proteases or host proteases? Why is this important?

Answer 5

Viral, which makes them a good target for drugs

Question 6

What genomes are more stable RNA or DNA viruses?

Answer 6

DNA viruses

Question 7

What is a possible advantage of high viral mutation rates.

Answer 7

It helped us to create live attenuated viruses that would maintain antigens to cause immunity but would be less virulent in humans

Question 8

What are the four possible viral interactions that can happen if two viruses infect the same cell?

Answer 8

Complementation
Phenotypic Mixing
Recombination
Reassortment

Question 9

describe viral complementation

Answer 9

When two defective viruses complement each others deficiencies and together are viable…the progeny however are the same as the two original viruses

Question 10

Describe phenotypic mixing of similar viruses

Answer 10

Two viruses that infect the same cell may acquire protein coats from the other virus. While each virus maintains its original genome, its phenotype may be altered such that it can infect a new cell type. This only lasts for one generation. (The altered phenotype viruses are called pseudotypes)

Question 11

Describe recombination of 2 viruses.

Answer 11

2 viruses that infect the same cell that happen to have extended homologous sequences can cross over. This results in a permanently altered chimeric genome.

Question 12

Describe reassortment of viral genomes?

Answer 12

If two segmented viruses enter the same cell, segments from each may be mixed when the other when encapsulation occurs resulting in a new combination of segments. (creates new strains of flu that cause the outbreaks)

Question 13

How can viruses cause genomes in host cells to mutate?

Answer 13

By insertion into the host genome

Question 14

Why is infection by 2 viruses rare?

Answer 14

Blocking of receptors
Competition for Resources
stimulation of innate immunity (interferons)
all of this caused by first virus usually prevents second virus from entering

Question 15

How many genes can feasibly be delivered by viral gene therapy?

Answer 15

only 1-2, any more gets too complicated at this point.

Question 16

What are the steps in developing a viral gene therapy?

Answer 16

1 Deletion of essential gene in virus and insertions of that essential gene into a packaging cell
2 Clone the therapeutic gene to virus
3 grow the virus in the packaging cell (Via complementation)
4 Test in cells - animals - humans

Question 17

What are some disease that lack a single gene that may be treated with viral gene therapy?

Answer 17

Cystic fibrosis
combined immunodeficiency
hemophilia
various enzyme deficiency disorders

Question 18

What two types/classes of diseases are particular targets for viral gene therapy?

Answer 18

Single gene disorders and cancer therapy

Question 19

What are some of the obstacles that have been encountered in viral therapy?

Answer 19

1 non-replicating Virus is not spreading in tumors (possibly add promoters that make them only grow in target cells)
2 only transient expression of foreign gene
3 low efficiency of gene transfer (need a ton of virus)
4 Inflammation in response to the virus
5 potential for chromosomal disturbances by virus

Question 20

Who is jesse gelsinger

Answer 20

18 yo with single gene deficiency (Orinthine transcarbamylase deficiency) given adenovirus gene therapy and developed ARDS and died