Viral Genetics 12/7/2018

Hepatitis Viral diseases Polio Measles Chicken pox 12/7/2018

30-40 million deaths world-wide Influenza: 1918 epidemic 30-40 million deaths world-wide RNA virus 12/7/2018

Smallpox Eradicated in 1976 vaccinations ceased in 1980 at risk population? 12/7/2018

Emerging viruses Viruses that “jump” host SARS hantavirus Ebola switch species Ebola, SARS, bird flu, hantavirus Ebola hantavirus SARS = Severe Acute Respiratory Syndrome 12/7/2018

 SARS (severe acute respiratory syndrome), a recently emerging viral disease (a) Young ballet students in Hong Kong wear face masks to protect themselves from the virus causing SARS. (b) The SARS-causing agent is a coronavirus like this one (colorized TEM), so named for the “corona” of glycoprotein spikes protruding from the envelope.

A sense of size Comparing size eukaryotic cell bacterium virus 12/7/2018

T4 bacteriophage infecting an E. coli cell 0.5 m

What is a virus? Is it alive? DNA or RNA enclosed in a protein coat Viruses are not cells Extremely tiny electron microscope size smaller than ribosomes ~20–50 nm 1st discovered in plants (1800s) tobacco mosaic virus couldn’t filter out couldn’t reproduce on media like bacteria 12/7/2018

Variation in viruses Parasites lack enzymes for metabolism plant virus pink eye Parasites lack enzymes for metabolism lack ribosomes for protein synthesis need host “machinery” 12/7/2018

(a) Tobacco mosaic virus Viral structure 18  250 mm 70–90 nm (diameter) 80–200 nm (diameter) 80  225 nm 20 nm 50 nm (a) Tobacco mosaic virus (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4 RNA Capsomere of capsid DNA Capsomere Glycoprotein Membranous envelope Capsid Head Tail fiber Tail sheath

Viral genomes Viral nucleic acids DNA RNA Linear or circular double-stranded single-stranded RNA Linear or circular smallest viruses have only 4 genes, while largest have several hundred 12/7/2018

Viral protein coat Capsid crystal-like protein shell 1-2 types of proteins many copies of same protein 12/7/2018

Viral envelope Lipid bilayer membranes cloaking viral capsid HIV envelopes are derived from host cell membrane glycoproteins on surface HIV 12/7/2018

Virus Invasion  

Generalized viral lifecycle Entry virus DNA/RNA enters host cell Assimilation viral DNA/RNA takes over host reprograms host cell to copy viral nucleic acid & build viral proteins Self assembly nucleic acid molecules & capsomeres then self-assemble into viral particles exit cell 12/7/2018

Symptoms of viral infection Link between infection & symptoms varies kills cells by lysis cause infected cell to produce toxins fever, aches, bleeding… viral components may be toxic envelope proteins Damage? depends… lung epithelium after the flu is repaired nerve cell damage from polio is permanent 12/7/2018

Viral hosts Host range most types of virus can infect & parasitize only a limited range of host cells identify host cells via “lock & key” fit between proteins on viral coat & receptors on host cell surface broad host range rabies = can infect all mammals narrow host range human cold virus = only cells lining upper respiratory tract of humans HIV = binds only to specific white blood cells 12/7/2018

Bacteriophages Viruses that infect bacteria ex. phages that infect E. coli lambda phage 20-sided capsid head encloses DNA protein tail attaches phage to host & injects phage DNA inside 12/7/2018

Bacteriophage lifecycles Lytic reproduce virus in bacteria release virus by rupturing bacterial host Lysogenic integrate viral DNA into bacterial DNA reproduce with bacteria 12/7/2018

The lytic cycle of phage T4, a virulent phage Attachment. The T4 phage uses its tail fibers to bind to specific receptor sites on the outer surface of an E. coli cell. Entry of phage DNA and degradation of host DNA. The sheath of the tail contracts, injecting the phage DNA into the cell and leaving an empty capsid outside. The cell’s DNA is hydrolyzed. Synthesis of viral genomes and proteins. The phage DNA directs production of phage proteins and copies of the phage genome by host enzymes, using components within the cell. Assembly. Three separate sets of proteins self-assemble to form phage heads, tails, and tail fibers. The phage genome is packaged inside the capsid as the head forms. Release. The phage directs production of an enzyme that damages the bacterial cell wall, allowing fluid to enter. The cell swells and finally bursts, releasing 100 to 200 phage particles. 1 2 4 3 5 Phage assembly Head Tails Tail fibers

Lysogenic lifecycle of phages 12/7/2018

Lysogenic Virus: Herpes 12/7/2018

Herpetic Whitlow http://www.nlm.nih.gov/medlineplus/ency/imagepages/1373.htm 12/7/2018

Herpes Simplex II 12/7/2018

RNA viruses Retroviruses have to copy viral RNA into host DNA enzyme = reverse transcriptase RNA  DNA  mRNA host’s RNA polymerase now transcribes viral DNA into viral mRNA mRNA codes for viral components host’s ribosomes produce new viral proteins protein RNA DNA transcription translation replication 12/7/2018

Retroviruses HIV Human ImmunoDeficiency Virus causes AIDS Acquired ImmunoDeficiency Syndrome opportunistic diseases envelope with glycoproteins for binding to specific WBC capsid containing 2 RNA strands & 2 copies of reverse transcriptase 12/7/2018

Retrovirus 12/7/2018

HIV infection HIV enters host cell macrophage & CD4 WBCs cell-surface receptor reverse transcriptase synthesizes double stranded DNA from viral RNA high mutation rate Transcription produces more copies of viral RNA translated into viral proteins proteins & vRNA self-assemble into virus particles released from cell by “budding” or by lysis 12/7/2018

Reverse Transcriptase 12/7/2018

Prions Misfolded proteins infectious make plaques (clumps) & holes in brain as neurons die Creutzfeldt-Jakob disease “mad cow” disease 12/7/2018