Chapter 18 Viral Genetics http://www.jackson.k12.ga.us/teachers/jawall/APBio.html Viral replication differs from other reproductive strategies and generates genetic variation via various mechanisms. Highly efficient replicative capabilities allowing for rapid evolution and acquisition of new phenotypes Replicate via a component assembly model allowing one virus to produce many progeny simultaneously Lytic cycle Allows for mutations to occur through usual host pathways RNA viruses lack replication error-checking mechanisms Higher rate of mutation Related viruses can combine/recombine info if they infect same host cell HIV is a rapid evolving virus within a host and contributes to the pathogenicity of viral infections 2/22/2019

Hepatitis Viral diseases Polio Measles Chicken pox 2/22/2019

30-40 million deaths world-wide Influenza: 1918 epidemic 30-40 million deaths world-wide RNA virus 2/22/2019

Smallpox Eradicated in 1976 vaccinations ceased in 1980 2/22/2019

Emerging viruses SARS hantavirus Ebola Viruses that “jump” host appear suddenly or suddenly come to the attention of medical scientists switch species Ebola, SARS, bird flu, hantavirus Ebola hantavirus SARS = Severe Acute Respiratory Syndrome 2/22/2019

Scene from the 2003 SARS Scare

 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 2/22/2019

T4 bacteriophage infecting an E. coli cell 0.5 m

What is a virus? Is it alive? Viruses do not really fit our definition of living organisms since viruses can reproduce only within cells DNA or RNA enclosed in a protein coat Viruses are not cells Extremely tiny electron microscope size smaller than ribosomes ~20–50 nm Viruses do not really fit our definition of living organisms Since viruses can reproduce only within cells They probably evolved after the first cells appeared, perhaps packaged as fragments of cellular nucleic acid 1st discovered in plants (1800s) tobacco mosaic virus couldn’t filter out couldn’t reproduce on media like bacteria 2/22/2019

Infection by tobacco mosaic virus (TMV) Tobacco mosaic disease Stunts the growth of tobacco plants and gives their leaves a mosaic coloration

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” 2/22/2019

Variation in viruses influenza bacteriophage A package of genes in transit from one host cell to another “A piece of bad news wrapped in protein” – Peter Medawar 2/22/2019

(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 Highly efficient replicative capabilities allowing for rapid evolution and acquisition of new phenotypes Replicate via a component assembly model allowing one virus to produce many progeny simultaneously Lytic cycle Allows for mutations to occur through usual host pathways RNA viruses lack replication error-checking mechanisms Higher rate of mutation Related viruses can combine/recombine info if they infect same host cell HIV is a rapid evolving virus within a host and contributes to the pathogenicity of viral infections 2/22/2019

Viral protein coat Capsid crystal-like protein shell 1-2 types of proteins many copies of same protein 2/22/2019

Viral envelope Lipid bilayer membranes cloaking viral capsid HIV envelopes are derived from host cell membrane glycoproteins on surface HIV 2/22/2019

Virus Invasion  

General Features of Viral Reproductive Cycles Viruses are obligate intracellular parasites They can reproduce only within a host cell Each virus has a host range A limited number of host cells that it can infect

Self-assembly of new virus particles and their exit from cell Viral Replication Viruses use enzymes, ribosomes, and small molecules of host cells To synthesize progeny viruses Highly efficient replicative capabilities allowing for rapid evolution and acquisition of new phenotypes Replicate via a component assembly model allowing one virus to produce many progeny simultaneously Lytic cycle Allows for mutations to occur through usual host pathways Bacterial cells divide by binary fission RNA viruses lack replication error-checking mechanisms Higher rate of mutation Related viruses can combine/recombine info if they infect same host cell VIRUS Capsid proteins mRNA Viral DNA HOST CELL DNA Capsid Figure 18.5 Entry into cell and uncoating of DNA Transcription Replication Self-assembly of new virus particles and their exit from cell 2/22/20192/22/2019

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 Highly efficient replicative capabilities allowing for rapid evolution and acquisition of new phenotypes Replicate via a component assembly model allowing one virus to produce many progeny simultaneously Lytic cycle Allows for mutations to occur through usual host pathways RNA viruses lack replication error-checking mechanisms Higher rate of mutation Related viruses can combine/recombine info if they infect same host cell HIV is a rapid evolving virus within a host and contributes to the pathogenicity of viral infections 2/22/2019

Mechanisms of Gene Transfer and Genetic Recombination in Bacteria Three processes bring bacterial DNA from different individuals together Transformation Transduction Phages carry bacterial genes from one host cell to another Conjugation

Transduction Figure 18.16 Phage DNA 1 Donor cell Recipient cell A+ B+ B– A– Recombinant cell Crossing over Phage infects bacterial cell that has alleles A+ and B+ Host DNA (brown) is fragmented, and phage DNA and proteins are made. This is the donor cell. A bacterial DNA fragment (in this case a fragment with the A+ allele) may be packaged in a phage capsid. Phage with the A+ allele from the donor cell infects a recipient A–B– cell, and crossing over (recombination) between donor DNA (brown) and recipient DNA (green) occurs at two places (dotted lines). The genotype of the resulting recombinant cell (A+B–) differs from the genotypes of both the donor (A+B+) and the recipient (A–B–). 2 3 4 5 Phage DNA

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 2/22/2019

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 2/22/2019

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 2/22/2019

Bacteriophage lifecycles Lytic reproduce virus in bacteria release virus by rupturing bacterial host Lysogenic integrate viral DNA into bacterial DNA reproduce with bacteria Highly efficient replicative capabilities allowing for rapid evolution and acquisition of new phenotypes Replicate via a component assembly model allowing one virus to produce many progeny simultaneously Lytic cycle Allows for mutations to occur through usual host pathways RNA viruses lack replication error-checking mechanisms Higher rate of mutation Related viruses can combine/recombine info if they infect same host cell HIV is a rapid evolving virus within a host and contributes to the pathogenicity of viral infections 2/22/2019

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 2/22/2019

Lysogenic Virus: Herpes 2/22/2019

Herpetic Whitlow http://www.nlm.nih.gov/medlineplus/ency/imagepages/1373.htm 2/22/2019

Herpes Simplex II 2/22/2019

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 Figure 18.9 Reverse transcriptase Viral envelope Capsid Glycoprotein RNA (two identical strands) 2/22/2019

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 rapid evolving virus within a host and contributes to the pathogenicity of viral infections 2/22/2019

Retrovirus 2/22/2019

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 2/22/2019

Reverse Transcriptase 2/22/2019

Viroids and Prions: The Simplest Infectious Agents Are circular RNA molecules that infect plants and disrupt their growth Prions Are slow-acting, virtually indestructible infectious proteins that cause brain diseases in mammals

Prions Misfolded proteins infectious make plaques (clumps) & holes in brain as neurons die Creutzfeldt-Jakob disease “mad cow” disease 2/22/2019

Review Questions

Viruses are not classified as prokaryotes because: They contain membrane bound organelles They are multicellular They are unicellular They are acellular They lack genetic material

Which of the following can be found in all viruses: Ribosomes RNA DNA A Protein Coat Cell membrane

The virus HIV replicates using reverse transcriptase The virus HIV replicates using reverse transcriptase. Thus it can be inferred that the virus Uses only DNA Uses only RNA Uses RNA as a template for DNA Uses DNA as a template for RNA Replicates continuously