November 21st notes

1. Classification of viruses
a. Viruses classified based on host cell
i. Ex: bacteriophagesinfect bacteria
ii. Ex: enterovirusinfect cells of the digestive tract
b. Even within a particular host organism, particular viruses only infect certain host cell types (have very narrow host ranges)
i. Ex: HIV only infects tiny subsets of human immune system cells (CD4+ T-Cells)
c. Traits a disease must have to be potentially eradicable
i. Be completely dependent on a human host for its reproduction
ii. Must have way of preventing new infections (Ex: vaccine) *to break cycle of infection*
iii. Must have a way of knowing who has disease *to break cycle of infection*
2. Virus structure *see handout*
a. Nucleic acid
i. Some viruses have DNA genomes, some have RNA genomes
ii. Virus genomes come in a variety of sizes; but are generally smaller than bacterial genomes
iii. because of programmed ribosomal frameshifting may have more genes than usually assigned in viral genome
1. picorna (viruses-small genomes made out of RNA)-polio has ~3,000base pairs in genome; ~3 genes and then it uses the rest from host
2. poxviruses-(viruses-small genomes made out of DNA)-smallpox, cowpow (used as vaccine for smallpox) have about ~300,000base pairs; ~300 genes
iv. viroid-loop of self-replicating DNA
1. ex: hepatitis D
b. protein coat
i. capsid
ii. capsomeres-repeating protein subunits that make up capsid
1. interactions between capsomeres determines the shape of virus
iii. Viral shapes
1. Polyhedral-like a soccer ball; lots of faces of 3-D object; all faces have identical shape
2. Helical-tube shape from capsomeres wrapping around each other like a telephone cord
3. Complex-polyhedron attached to helicase; only infect bacteria NEVER eukaryotes
c. Enveloped viruses also have a membrane, derived from host cell membrane (note: enveloped viruses only infect eukaryotic cells)
d. Glycoproteins: attach membrane to capsid of enveloped virus, allow virus to attach to host cell. Glycoprotein= part of envelope virus we have immune response against. Ex. HIV, Flu, Herpes family- herpes simplex I, chicken pox, STD herpes.
e. Virion=singular virus particle
3. Viral Replication
a. Attachment/adsorption – Virus must bump randomly into an appropriate host cell. In 1:10 ^4 bumps virion will transiently stick to surface of host cell. IF viral surface proteins are the right shape to interact with cell surface receptors, tighter junction between virion and host cell formed. Only some host cells are specific to particular host cells because only some kinds of cells have “correct” surface proteins for viral proteins to attach to. IF there is a tight junction formed with virion, cell engulfs virion. If enveloped virus, its membrane fuses with new host membrane. If not enveloped, virion just engulfed by host cell, brought into cell’s lysosome.
b. Penetration/ decoding: lysosome of cell contains digestive enzymes, low ph and breaks down proteins that make up capsid of virion . This frees the nucleic acid to be copied by host cell. IN case of complex- shaped bacteriophage, virus attaches to recptors on back surface, injects DNA into bacteria, leaving capsid o bacterium.
c. Viral nucleic acids copied by host cell enzymes etc.
i. DNA viruses- ex. Smallpox, HPV, have DNA genomes
1. Host cell DNA polymerase copies viral DNA
ii. RNA viruses- Have RNA genomes- ex. Flu
1. But no living thing has an enzyme that copies RNA to RNA
2. RNA replicase: RNA- virus specific enzyme that copies RNA to RNA.
a. First step in copying RNA: translation of RNA replicase gene by host cell ribosome
iii. Retro viruses (ex. HIV)- also have RNA genomes.RNA genome is copied into DNA copy ( reverse transcriptase, enzyme specific to retroviruses because it copies RNA  DNA) and then DNA copy is integrated into hosts DNA. Then DNA copy is copied back into RNA by the host enzymes (RNA polymerase).
d. Synthesis of viral proteins
i. Virus uses host RNA polymerase, ribosomes, tRNA, t amino acids to make its capsomeres, glycoproteins, other viral specific proteins.
ii. Ex. HIV host cell= CD4 + T cells, a kind of immune cell. No longer able to make chemicals to keep safe from infection.
iii. Ex. Polio host cell=infects intestine epithelia (wont affect much cuz we make more a lot), motor neurons . Cant do motor neurons things including producing proteins communicating with muscles, instead makes viral things.
e. Assembly of viral proteins

i. Once you have all the ingredients, new virions will spontaneously self assemble.
ii. Wimmer (2003): Synthesized polio genome took RNA polio genome and put it in host cell, got new virions.
f. Release of virions from host cell
i. Lysis of host cell (very uncommon, kills host cell): host cell blows up, releases new virions into environment.
ii. Budding form host cell: Enveloped viruses use glycoproteins to wrap selves in host cell membrane and tear free.
4. Consequences of viral infection on host cell
a. Death of Cell
i. Virus directly kills host cell. Ex. T4 phages and E.coli- only way for new T4 virions to escape host cell is to lyse cell. T4 can only survive in environment with lots of E. coli.
ii. Viral replication so compromises host cell functions that cell dies.
iii. Cell infected with virus may be killed by immune system. Ex. CD4 + cells alert immune system to other cells infected with viruses, immune system then kills virus and infects cells.
b. Disruption of cell function: because cell enzymes, ribosomes makin new virons, not cells on proteins.
c. Normal Cell ( Divide 30 times, divide on own schedule, commit suicide (aptosis) with DNA damage, infection cancerous cell
i. Cancer cells divide more rapidly
ii. Divide forever
iii. Don’t commit suicide
iv. HPV: types 16+18 produce proteins that turn off a cells ability to commit suicide
5. Viral Culture (to make vaccine), to test anti-viral meds.
a. How are we going to grow virus? Animals or animal cells- because viruses need a host cell.
i. Infect animal, harvest viral particles from animal.
ii. “immortalized” Human cells: Henrietta Lacks and HeLa cells- human celss can grow in liquid similar to blood plasma.
1. Normal cells only commit suicide after about 30 divisions.
2. So uses cancer cells to grow viruses.
3. Henrietta Lacks died of cervical cancer. She is the contributor of heLa Cells: divide forever, used worldwide to grow viruses. Mrs. Lacks died of HPV-18 but this allowed us technology to defeat HPV 18.

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