what is a virus

• obligate intracellular parasites - need a host cell

• submicroscopic dimensions (20-300nm) - no own proteinbiosynthesis

• genome of either RNA or DNA surrounded by proteins

• no own energy metabolism

• capable of reproducing in a host cell

• disintegrate into their components after infection of the host cell

• newly formed by the aggregation of produced components

virion - infectious partiel - kind of alive but not. protein, lipids, NS

virus lat - poison

165-180 antoine plague in the roman empire - smallpox (variola)

1546 description of food&mouth disease by Girolamo Fracastoro

1748 description of canine distemper by don antonio de ulloa

1789 1th vaccination against human smallpox by edward jenner

wenn es sich nun nachweisen ließe:

1. the microorganism must be found in abundance in all organisms suffering from the disease, but should not be foung in healthy organisms

2. the microorganism must be isolated from a diseased organism and grown in pure culture

3. the cultured microorganism should cause disease when introduced into a healthy organism

4. the microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

• Adolf mayer

  • first desribed the tabacco mosaic disease

  • could be tranferred etween plants, similat to bacterial infections -> transfer due to infectious agents.

• dimitri iwanoski

  • infected sap remained infectious even after filtering through the finest chamberland filters

  • dilution to exclude any poison

• martinus beijerinck

  • ultra-filterable agens -> got the virus away

  • “contagium vivum fluidum”

• wendell stanley

  • tabacco mosaic virus was the first virus to be crystallized

• kausche, pfankuch, ruska

  • first electron microscopical images of TMV

1. nature & sequence of NA in viron -> RNA or DNA

2. symmetry of protein shell (capsid) -> when NA is isolated- protects the genome

3. presence or absence of lipid membrane -> outer appearance (membrane/envelope or non-enveloped (nothing))

4. dimension of virion and capsid

• DNA or RNA

• NS: ds or ss -> big impact in infection cycle

• envelope: yes/no -> entry mechanism is different

• geometry / symmetry of the capsid -> final view of the virus

• polarity of RNA: + or - -> sensed positive or negative - need - to read up the +

• RNA segment or not segmented -> coild lead to new variants -> could be easily transferred/exchanged between 2 viruses

Viruses:

order - virales

family - viridae

genus - virus

species

e.g. - ebola: Fam- mono (ssRNA) nega (-) virales

Filo(appearence)viridae (filofam.)

ebolavirus

zaire(kongo) ebolavirus

cubical symmetry - icosaeder

helical symmetry -> 2 major symmetries -> made of helical RNA and proteins on the outside to protect (e.g. TMV; Influenza - RNA virus with helical capsid surrounded by an envelope spikes)

• capsids can be covered by host membranes: enveloped virions

• capsids are partially surrounded by an envelope

• lipid double memrbane: cellular origin

• incoroperated viral glycoproteins: important for binding and infection of host cells -> important AGs for immune defense

• sensitive for inactivation by solvents and detergents

• structural: are components of the mature virus particle (“virion”)

• non-strucutral: are synthesized in infected cells but not incorporated into new virus particles (-> replication, immune evasion (proteins))

synthesisedfor the reproductive cycle

functions of structural proteins:

• protection of the genome:

  • assembly of a stable protective protein shell

  • specific recognition and packagin of the nucelic acid genome

  • interaction with host cell membranes to form the envelope

• delivery of the genome

  • bind host cell receptors

  • uncoating of the genome

  • fusion with cell membranes

  • transport of the genome to the appropriate site

• non strucutral proteins

  • enzymes - polymerases, integrases, assosiated proteins, proteases, PolyA polymerase

for intracellular parasites!

1. infection: attachement - entra, penetration - uncoating

2. replication: transcription - protein-synthesis (many enzymes produced) - genome-synthesis

3. building of new virions: assembly - maturation - release

virus gets in contact with specific cell - this is why its receptor mediated endocytosis

capsid needs to get into the genome

some viruses aquire specific enzymes

• viruses are obligated intracellular parasites!

• virus particles are too large to diffuse across the plasma membrane

• finding the “right” cell receptor

1. adhere to cell surface (electrostatics) No specificity!

2. attach to specific receptor molecules on cell surface - more than one receptor may be involved

3. transfer genome inside the cell

essential for all viruses except those of fungi (no extracellular phase) and plants (enter cells by mechanical damage)

receptor mediated endocytosis

interaction between surface molecules

• A susceptible cell has a functional receptor for a given virus - the cell may or may not be able to support viral replication

• a resistant cell has no receptor - it may or may not be competent to support viral replication

• a permissive cell has the capacity to replicate virus - it may or may not be susceptible

• a susceptible AND permissive cell is only cell hat can take up a virus particel and replicate it

fusion: of viral envelope and cell membrane

endocytosis: entrapment of the viral particle in a cellular vacuole

release of the viral genome from capsid/viral envelope

intracellular parasites!

Replication/Eklipse

• ranscription

• protein-synthesis

• genome synthesis

key fact makes your life easier: viral genomes ust make mRNAthat can be read by most ribosomes

All viruses on the planet follow this rule, no known exceptions

with every viral replication, mRNA (positive polar RNA) must be produced

• + DNA -> +/- DNA -> +mRNA -> -RNA

retroviren - +RNA ->-DNA -> +/-DNA

paroviren & hepadnaviren -(herpes & pocken) +/- DNA

Flaviviren - +RNA -> -RNA -> +mRNA

Reoviren -> +/-RNA

Paramyxo- und Orthomyxviren -> -RNA

• RNA viruses mostly replicate in the cytoplasm (exception: influenza virus, bornavirus - need splicing apparatus!)

• RNA viruses (exception: retrovirueses) need an RNA-dependent RNA polymerase (RdRp)!

• Eukaryotic host cells dont possess such an enzyme!

• RdRp must be brought along by the RNA viruses

• as a finished protein in the virus particle (RNA viruses of negative polarity) as a gene (RNA viruses of positiv polarity)

Morphogenesis

• assembly

• maturation

• release

viral envelope has cellular origin

budding: envelopment of capsids with cellular lipid membranes

model for escrt-independent buddong by influenza virus:

->interaction of RNs with HN and HA proteins forms a bud at the cell surface

-> the buds grows with HA proteins gathering in the tubule part

-> M2 viroporin depolarizes the membrane, resulting in a decrease of membrane repulsion between oposing monolayers at the neck of the budding site

->this conformation resolves by fission of the virion particle

via - lysis -> non-enveloped virion

budding - bu cellular exocytosis or via plasma membrane -> enveloped virion

cell to cell transport - syncytium, nanotubules, fungus hyphal anastomosis

e.g. cleavage of precursor proteins, “activation” of ligands

• invention of the “supermicroscope” (=electron microscope) by the Ruska brothers

• 1939 - first review on the strucure of viruses

• 40 - visualization of bacteriophage lysis

• 43 - proposal for virus taxonomy according to morphological criteria

animal viruses at first couldnt be routinely propagated in cultured cells

most viruses were grown in laboratory animals

• cultivation on viruses in egg -> chorioallantoic membrane inoculation -> HPV, Poxvirus, Rous saroma V

• amniotic inoculation -> influnza, mumps

• Yolc sack inoculation -> HPV

• Allantoic inoculation -> Influenza, mumps, newcastle disease V, Avian adenov.