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Viruses: intimate parasites • Are viruses alive? – – – – Not made of cells, in violation of Cell Theory Do not grow (but self assemble) Do not metabolize (but steal energy) Cannot reproduce w/o a host cell (but other organisms may require another species in order to reproduce) – Can evolve over time – Some can respond to environmental stimuli – Have a complex, organized structure 1 If not cells, then what? • Viruses are particles • Some components are essential – A genetic material with the blueprint for making more • Could be: ds DNA, ss DNA, ss RNA, ds RNA • Space is limited, so genes are few – A covering to protect the genetic material • Capsid, made of one or more proteins • Capsid + nucleic acid: nucleocapsid • Viruses are obligate intracellular parasites 2 Viruses may have other parts • Envelope: piece of organelle or cell membrane covering capsid – Virus is formed by budding, pushes through membrane taking a piece. – Viral envelope usually contains viral proteins. – Envelope makes virus susceptible to some disinfectants • Spikes (peplomers) extend from envelope – Used for attachment, escape • Accessory enzymes – Reverse transcriptase, RNA RNA enzymes 3 Viral size and shape • Viruses range from 30 nm to 300 nm – Ribosomes are about 30 nm – The smallest known bacteria are about 200 nm • Viral shapes: – helical, polyhedral, and complex http://www.glencoe.com/qe/images/b136/q4323/ch18_0_a.jpg; www.blc.arizona.edu/.../ Figures/Icos_Virus.GIF; http://www.foresight.org/Updates/Update48/Images/T4Schematic.jpg 4 Examples of virus shapes Ebola Adenovirus http://www-cgi.cnn.com/HEALTH/9604/16/nfm/ebola.levine/ebola.reston.large.jpg; http://www.virology.net/Big_Virology/EM/Adeno-FD.jpg 5 Specificity • A recurring theme in biology: – Enzymes, membrane receptors, antibodies, etc. • Viruses are limited to certain types of host cells – Species barriers: rabies not specific, but most are – Tissue type: rabies specific to nerve, salivary tissue – Cell type: HIV infection mostly restricted to Helper T cells, a kind of lymphocyte. • Different characteristics of host cells involved – Attachment to cell surface often a major point • Every type of organism has a virus that infects it? 6 Classification • Microbes problematic, viruses especially so. – No sexual reproduction, no asexual reproduction, just “assembly”. – No clear evolutionary relationships • Classification scheme (from David Baltimore) – First, by nucleic acid type, e.g. ds DNA, + sense RNA – Next, structural characteristics (presence of envelope, capsid shape), type of organism infected, etc. 7 Life cycle of a virus • Manner of infection and reproduction depends on whether host is prokaryotic or eukaryotic. • Life cycle here outlined is general: – ADSORPTION: following contact, molecules on surface of virus bind to particular molecules on host cell. – PENETRATION: the nucleic acid must get access to the machinery of the cell to replicate. http://www.tthhivclinic.com/Fig_20.gif 8 Life cycle continued 9 • SYNTHESIS/REPLICATION: once inside the nucleic acid issues orders leading to – Replication of the nucleic acid – Transcription (usually) and translation, producing the necessary capsid proteins. • ASSEMBLY: a spontaneous process – Capsid proteins and nucleic acid combine to make virion. – Cheap but highly inefficient process. • RELEASE: successful parasite must spread to others – Virus causes lysis of cell or pushes through cell membrane. Virions may acquire an envelope. Measuring numbers of virions: the Plaque Assay •Virus and host cells are mixed •Bacteria cover in a Petri dish as a “lawn”, eukaryotic cells cover bottom of a dish. •Multiplication of virus leads to release, spread to and destruction of nearby cells. •Visible as holes, plaques, on bacterial lawn; eukaryotic cells in culture are first stained for easier view to see plaques. http://dept.kent.edu/biology/Courses/30171/imageQBT.JPG; news.bbc.co.uk/.../ _230333_cell_culture_300.jpg; 10 Bacteriophage: lytic vs. lysogenic 11 • Most bacteriophages multiply then lyse the host cell – This life cycle is called a lytic cycle • Others are “temperate”, enter a lysogenic cycle. – Lysogeny is an effective way to multiply the viral DNA – Viral DNA inserts into the bacterial chromosome • Now called a “prophage” • Bacterial replication also replicates viral DNA • Prophage may bring new genes for use by bacterium – Damage to bacterial DNA (e.g. UV) prompts virus to begin lytic cycle; DNA excises, virus multiplies. Growing viruses • Obligate intracellular parasites: require a host cell!! • Whole organism – Animal models, human volunteers • Ethically, humans require consent, safety, pay • Eggs: aseptic incubator – Various cells and membranes support growth of viruses – Shell provides protection from bacterial contamination – Used for large batches of viruses for vaccines • Egg allergies a problem sometimes http://www.fao.org/ag/againfo/foto/egg-facts.gif 12 Growing viruses continued 13 • Organ/tissue/cell culture – Minced tissue, separated into cells by enzyme treatment – Grown in sterile plastic dish with nutrient solution – Cells prepared this way grow until dish is covered, stop. • Scrape up, use some to inoculate new culture • Limited number of rounds of replication – Transformed cells, with cancer properties, grow forever. • Must be subcultured when dish bottom is covered • Cell culture major reason for advances in virology Viruses and disease 14 • Most of discomfort, some of damage, is due to host defense response to viral infection. • Cytopathic effects: damage caused by viruses – Cells change shape, change size (round up, swell) – Cells become sticky (clump, fuse to form syncytia) • Syncytia are giant, multinucleated cells – Cells change internally (vacuoles, inclusions) • Location, appearance of inclusions characteristic of certain viruses; comprised of viral parts or cell debris – Cells die. Other effects of viruses • Transformation: cells become cancer-like – – – – Lose contact inhibition Continue to multiply In vivo, produce tumors Certain Herpes-type viruses, genital wart virus, etc. • Some viruses cause birth defects = teratogenesis – Damage to critical cells in fetus, failure to form parts – Typically, virus is mild and able to cross placenta – Rubella (German measles virus), CMV 15 NOT viruses • Viroids: naked RNA – Cause of infectious disease in plants • Prions: infectious protein particles – Got Stanley Prusiner the Nobel Prize, but still controversial. – Cause of Mad Cow Disease, Scrapie, Elk Wasting disease, Creutzfeldt-Jakob disease, Kuru, etc. – Transmissible spongioform encephalopathies – Misshapen protein causes normal protein to also fold incorrectly, increasing their numbers – Replication without the presence of nucleic acid 16