Viral Genomes and Genetics

Hershey-Chase exprimnted with

phage T4

Fraenkel-Conrats expirmented with

TMV

Hershey-Chase Bacteriophage Experiment (1953)

The basis of this experiment is that DNA contains phosphorus but no sulfur, whereas proteins contain sulfur but virtually no phosphorus.

Fraenkel-Conrat (1957)

TMV was treated to two different strains with chemicals that dissociate the proteins coats of the virus from the RNA molecules and separated the proteins from RNA

viral genomes

makes mRNA that can be read by host ribosomes

How many types of viruses

uncountable

Growth of viruses

only grows within the cell and can only live if they are passed from host to host organism.

How we determine if our culture was infected by a virus

formation of plaque

Equilibrium viruses

have been long term parasites of a given species, they are generally not lethal but spread well

Example of equilibrium virus

1. Polio

2. Smallpox

3. Common Cold

4. Measles

5. herpes

Non-Equilibrium viruses

have recently jumped from another species. They are sometimes lethal and may spread well or not.

Non-equilibrium example

1. Influenza (bird)

2. SARS (bats)

3. Ebola (bats)

4. HIV (chimp)

5. Hantaan (rodent)

Discovery of Reverse Transcription (1960)

Howard Temin speculated that RNA tumo viruses could turn their RNA into DNA

Discovery of Reverse Transcription (1970)

Temin independently discovered that the RNA tumor virus particles contained a reverse transcriptase

Discovery of Reverse Transcription (1975)

They shared the Nobel Prize in Physiology or Medicine with Renato Dulbecco who had been a mentor to both research

Why is HIV lethal

a classic non-equilbrium virus that is endemic in African monkeys and jumped to humans around 90 years ago. it grows in and kills helper T cell, wiping out our immune systems.

What information is encoded in a viral genome

1. Replication of viral genome

2. Assembly and packaging of the genome

3. Regulation and timing of the replication cycle

4. Modulation of host defense

5. Spread to cells and hosts

What is the Information is not contained in viral genomes

1. No genes encoding the complete protein synthesis machinery

2. No genes encoding protein involved in membrane biosynthesis

3. No classical centromeres or telomeres found in standard host chromosome

4. Probably we havent found them yet - 90% of giant virus genes are novels

smallest known viral genomes

Barnavirus (RNA)

dsDNA genomes example

adenoviridae, herpesviridae, and poxviridae

Gapped dsDNA genomes

Hepadnaviridae and Hepatitis B virus

ssDNA genomes

Circiviridae and parvoviridae

RNA genomes

1. dominate the eukaryotic virosphere, rare in bacteria

2. Cells have no RNA-dependent RNA Polymerase

3. Viral genomes encode RdRp

4. RdRp produces RNA genomes and mRNA from RNA templates

dsRNA example

Rotavirus

ssRNA (+) example

picornaviridae, caliciviridae, coronaviridae, etc….

ssRNA (-)

Paramyxoviridae, Rhabdoviridae, Filoviridae, etc…

mutation

a change in DNA or RNA that may lead to amino acid substitutions, additions, or truncations in protein.

Genetic methods

production of infectious virus after transformation of cells by viral DNA, first done with bacteriophage lambda

Synthetic Virology and Biosecurity

infectious viral DNA enables experiments not previously possible

National Science Advisory Board for Biosecurity (NSABB)

Federal advisory committee to provide advice, guidance, and leadership regarding biosecurity oversight of dual use research

Naked Viruses

Enveloped Viruses

Hershey-Chase Bacteriophage Experiment (1953)

Frankel-Conrat Experiment

Plaques formed by Viruses

dsDNA genomes

Gapped dsDNA genomes

ssDNA genomes

dsRNA genome

ssRNA (+)

Retroviridae

ssRNA (-)

Reassortment: Consequence of segment genome

Infectious poliovirus DNA

Infectious influenza virus DNA