Lecture 1 Flashcards
(34 cards)
Why study viruses?
- Infect all living things
- Everywhere, we encounter billions of particles each day
- Outnumber cellular life 10:1
- Greatest biodiversity on Earth
- Make up 67.7% of our genome
- Important disease-causing agents although not all viruses make us sick
Tell me about the number of viruses on Earth
- Over 10 to the 31 bacteriophages
- 1 bacteriophage is a femtogram (10 to the -15 grams)
- 1000 fold more bacteriophages than elephants (in terms of biomass)
- 100 million light years if we put all bacteriophages head to tail
- More viruses in a liter of coastal seawater than there are people on Earth
Benefits of viruses
- Drive global life cycles: catalysis of the movement of nutrients from organisms, kill 20-40% of ocean microbes every day, important players in the regulation of the Earth’s ecology
- Gene transfer between organisms
- Prevent and cure diseases (ex: oncolytic viruses engineered to kill cancer cells)
What is CthTV?
This virus infects fungus called Curvularia protuberata and makes it thermotolerant, so when it colonizes Dichanthelium lanuginosum, this plant is now thermotolerant and can grow in soils at temperatures of 50 degrees or higher.
What is CthTV?
This virus infects fungus called Curvularia protuberata and makes it thermotolerant, so when it colonizes Dichanthelium lanuginosum, this plant is now thermotolerant and can grow in soils at temperatures of 50 degrees or higher.
The densovirus and aphid affair…
The rosy apple aphid gets infected and this triggers wing growth, there can then be lateral transfer of viral gene into Pea aphids who also grow wings, move to another plant, infect others, and then more and more wings woohoo.
The enteric virus and its power for good…
Germ free mice may develop abnormalities in their intestines due to the lack of beneficial commensal bacteria in the gut. When MNV, an enteric virus, infects them, the morphology can be restored.
The unique insights into cell biology that viruses offer
- Identification of promoters for eukaryotic RNA polymerases
- Cellular DNA replication enzymes
- Reverse transcriptase
- RNA dependent RNA polymerases
- RNA splicing
- Translation
- Identification of oncogenes
What is a virus?
An infectious, OBLIGATE intracellular parasite / It contains a genome (RNA or DNA, ss or ds), a protein capsid, and in some cases a lipid bilayer (envelope) / can also have other proteins as we will see later on
Size of viruses
- Nanometer scale
- Polio is bigger than bacterial ribosomes which are bigger than bacteriophage MS2
- Most viruses are a lot smaller than E.Coli which is smaller than RBCs
- Not as small as we once thought (used to use filters to see if infectious agent was bacterium or virus)
- some do not pass through pores
First giant virus discovered and subsequent discoveries
Mimivirus (mimics bacteria) 0.4-06. micrometers, afterwards mamavirus (mom of mimi)
- Pandoravirus 1 micron
- Pithovirus 1.5 microns (infects amoeba) almost as big as E.coli ( 2 microns long)
- We don’t know what their entire genomes do exactly (80% unknown)
How old are viruses?
- Evolution traces them back to at least dinosaurs, probably before, so billions of years
- Evidence in some Egyptian steles, polio like infection
- Smallpox pustules found on mummified pharaohs
- Rabid hector leads the charge in the Iliad (rabies)
- Nicolas Robert: three broken tulips, striped to indicate tulip mosaic virus (1600s)
The three theories on the origins of viruses
- Virus-first hypothesis: co-evolved or predate cellular hosts
- Regressive (or reduction) hypothesis: remnants of cellular organisms (fourth domain of life)
- Progressive (or escape) hypothesis: viruses arose from genetic elements that gained the ability to move between cells, autonomous replication of selfish cellular genes
What is the probably origin of viruses?
- Chimeric scenario for the origins of viruses: diversification of replicators and replication strategies from the ancestral RRM module, then acquisition of a protocapsid from selfish replicators from primitive cells, and then evolution and BAM virosphere
Are viruses alive (hint: inanimate or animate)?
- Inanimate molecular machines that exist as virions (inanimate phase) and as infectious viral particle in an infected cell (multiplying phase)
- They are passive and completely at the mercy of their environments, they do not synthesize on their own, they do not exhibit, display, destroy, evade or generate anything really
When and how did we first observe viruses?
In the 1930s, Tobacco mosaic virus, bacteriphage T4 and Vaccinia virus were observed with electron microscopy.
What are the 4 different ways in which we classify viruses?
- Based on nature and sequence of nucleic acid vision (hmmmm Baltimore wink wink nudge nudge)
- Symmetry of protein shell (capsid is helical? perhaps icosahedric? you knowww)
- Presence or absence of the envelope
- Dimensions of vision and capsid
How do viruses fit in the classical hierarchical system?
- Not alive so no kingdom, phylum or class
- Order (virales), family (viridae), genus (virus), species
- Example of rabies (bullet like structure): mononegavirales (ss - RNA), rhabdoviridae (fury), lyssavirus, rabies virus
Protovirology (1796-1885)
- Before viruses were recognized
- First hint or clues of virus existence without formal proving or anything
- Jenner cowpox/small pox 1798
- 1882: transmission of tobacco mosaic disease with cell-free extracts (Mayer)
- 1885: Rabies vaccine by King Pasteur by crushing rabies infected animal tissue and its desiccation
Auroravirology (1892-1933)
- The dawn of virology, recognition of what viruses really were
- Description of filterable infectious agent (Ivanovsky) 1892
- Concept of a virus as a contagious element (Beijernick, 1898)
- Foot and mouth disease virus (1st animal virus, Loeffler and Frosh, 1898)
- 1st human virus (yellow fever virus, Reed, 1901)
- Discovery of first solid tumour virus (Rous, 1911) (RED)
- Virus cultivation in tissue culture (Steindhart and Lambert 1913)
- Discovery of bacterial viruses (Bacteriophages, Twort, d’herelle, 1915)
Meridiovirology (1934-1955)
- Midday, Sequel to dawn also known as classic virology
- Bacteriophages are composed of nucleic acids and protein Schlesinger 1934
- Crystallization of TMV Stanley 1935 (RED)
- YFV vaccine theiler 1938 (RED)
- EM used to see viruses von berries, Ruska and Ruska 1938
- Genetic origins of mutations lurid and delberck 1943 (RED)
- Plaque assay of an animal virus (poliovirus) dulbecco 1952 (RED)
- Viral genomes are nucleic acids (Hershey, Chase, 1952) (RED)
Janovirology (1956-1975)
- Named for the god of endings and beginnings
- Virus particles are composed of identical subunits (Watson, crick, 1956)
- RNA carrying genetic information like DNA (schramm, fraenkel-conrat, williams, 1956)
- Studies of virus structure (Klug, Caspar, 1962) RED
- Discovery of viroids (diener, 1967)
- Hep B virus discovery (Blumberg, 1967) RED
- Discovery of retroviral reverse transcriptase (temin, Baltimore, 1970) RED
- 1st recombinant DNA molecules (berg, 1972) RED
- 1st Restriction map (Nathans, 1973) RED
Neovirology (1976-present)
- Dominated by viral sequence information
- 1st RNA genome sequences (fiers, 1976)
- 1st DNA genome sequenced (Sanger, fiers, weissman, 1977)
- Discovery of RNA splicing (Roberts, Sharp, 1977) RED
- Discovery of tumour suppressor p53 (Levine, Crawford, 1977)
- 1st infectious molecular clone of an RNA virus (weissman, 1978)
- Small pox eradication (WHO, 1979)
- 1st infectious molecular clones of animal viruses (Baltimore, 1981)
- 1st antivirals (Elion, Hutchings, 1982) RED
- Discovery of HIV (Montagnier, Barre-Sinoussi, Gallo, 1983)
- Discovery of Hep C virus (Alter, Houghton, Rice, 1989) RED
- Discovery of Gene silencing (Fire, Mello, 1998) RED
Why do we say infectious cycle?
Because there is no real start or end, it is a circle, the start is arbitrarily selected as the binding to receptor and entry
