2-19 Viral Genetics Flashcards Preview

Unit 2 > 2-19 Viral Genetics > Flashcards

Flashcards in 2-19 Viral Genetics Deck (10):
1

How do viruses encode their genomes?

  • DNA or RNA but not both
  • Single- or double-stranded
  • Linear or circular
  • One segment or multiple segments

Viruses have from 2 genes (as in parvoviruses) to 200 genes (as in pox viruses). This is too few for independent survival, and viruses depend on cellular genes to supply the missing functions.

2

How do viruses express genes?

As with bacteria or humans: genes = enhancer/promoter region + ribosomal entry site + open reading frame.

UNLIKE bacteria:

  • No operons
  • Expression is not induced by interaction between an operator and a repressor/inducer, but by binding of cellular transcription factors to promoter regions (thus, viruses are eukaryotic)

3

What kinds of viral genome structures are there?

  • Simple genomes: Genes in a linear arrangement on one RNA strand, with only a single promoter (e.g., retroviruses)
  • Complex genomes: Genes on both strands of DNA, often overlapping, and each with its own promoter (e.g., adenoviruses, herpesviruses, poxviruses)

4

How do viruses compress their functions into minimal space for maximal efficiency?

  • No non-coding regions
  • Overlapping reading frames
  • Translational frameshifts
  • Splices
  • Polyproteins, which are cleaved into individual proteins by specific proteases, which makes 1 promoter enough for an entire virus. (These proteases are unique to viruses and, therefore, potential drug targets, especially for HIV and hepatitis C.)

5

How common is viral mutation, and why?

Mutation frequency is high:

  • High error rate of polymerase
  • Lack of proofreading and error correction
  • Lack of second strand in some viruses
  • Small amount of genetic material, with no "waste"

DNA viruses are fairly stable, while RNA viruses are very unstable (1 mutation per generation).

6

Why are mutations important in viruses?

  • Allow epidemiological studies (e.g., MERS)
  • Allow live vaccines to be made (e.g., early polio vaccine; some mutations only allow a virus to grow under certain conditions)
  • Can produce new antigens which avoid immunity (e.g. influenza antigenic drift)
  • Can lead to drug resistance (e.g., protease of Hepatitis C)
  • Integration of viral genome can cause disease (e.g., papillomavirus in cervical cancer)

7

What can happen if two viruses infect one cell?

The infection of 2 viruses in 1 cell is uncommon, because one will usually preclude the other, but when it happens, 1 of 4 things may follow:

  1. Complementation of 2 defective viruses: neither can produce progeny virus alone, but together they can produce viable progeny virus A and viable progeny virus B
  2. Phenotypic mixing of similar viruses: 2 very similar viruses will produce progeny for virus A and B, but also some pseudotypes via exchange of capsid proteins (virus A w/ B characteristics, virus B w/ A characteristics), which only last 1 generation
  3. Recombination of homologous viruses: 2 homologues enter a cell and cross over during replication, producing progeny different from parents
  4. Reassortment of segmented viral genomes: 2 segmented viruses mix segments, producing progeny different from parents

8

Why are most cells/organisms only infected with one virus at a time (i.e., why is viral interaction rare)?

  • Blocking of receptors
  • Competition for resources
  • Stimulation of innate immunity

9

How would viruses be used in gene therapy?

  • Delete an essential gene from virus
  • Insert that gene into ‘complementing’ cell
  • Clone the therapeutic human gene into virus
  • Grow the virus in the complementing cell
  • Test virus in cells, animals, humans

Diseases that might be treated by gene therapy are mainly those with a congenital lack of a single gene/protein (e.g., CF, combined immunodeficiency, hemophilia, various liver enzyme-deficiency disorders).

Delivery of gene therapy by viruses involves host-range mutants, which can be made from retroviruses, adenoviruses, herpes simplex virus, and adeno-associated virus.

10

What are some problems associated with viral gene therapy?

  • Short duration of expression
  • Very high doses of viral vectors required (low efficiency of gene transfer)
  • Severe inflammation in response to the virus
  • Insertion of viruses into a recipient’s genome leading to malignant disease