Chapter 18

1. Chapter 18 Viruses and Gene regulation

2. Concept 18.1: A virus has a genome but can reproduce only within a host cell • Scientists were able to detect viruses indirectly • Long before they were actually able to see them

3. Figure 18.3 The Discovery of Viruses: Scientific Inquiry • Tobacco mosaic disease • Stunts the growth of tobacco plants and gives their leaves a mosaic coloration

4. In the late 1800s • Researchers hypothesized that a particle smaller than bacteria caused tobacco mosaic disease • In 1935, Wendell Stanley • Confirmed this hypothesis when he crystallized the infectious particle, now known as tobacco mosaic virus (TMV)

5. Structure of Viruses • Viruses • Are very small infectious particles consisting of nucleic acid enclosed in a protein coat and, in some cases, a membranous envelope

6. Viral Genomes • Viral genomes may consist of • Double- or single-stranded DNA • Double- or single-stranded RNA

7. Capsomereof capsid RNA DNA Capsomere Glycoprotein 18  250 mm 70–90 nm (diameter) 20 nm 50 nm (b) Adenoviruses Figure 18.4a, b (a) Tobacco mosaic virus Capsids and Envelopes • A capsid • Is the protein shell that encloses the viral genome • Can have various structures

8. Membranousenvelope Capsid RNA Glycoprotein 80–200 nm (diameter) 50 nm (c) Influenza viruses Figure 18.4c • Some viruses have envelopes • Which are membranous coverings derived from the membrane of the host cell

9. Head DNA Tail sheath Tail fiber 80  225 nm 50 nm (d) Bacteriophage T4 Figure 18.4d • Bacteriophages, also called phages • Have the most complex capsids found among viruses

10. 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

11. VIRUS DNA Entry into cell and uncoating of DNA Capsid Transcription Replication HOST CELL Viral DNA mRNA Viral DNA Capsid proteins Self-assembly of new virus particles and their exit from cell Figure 18.5 • Viruses use enzymes, ribosomes, and small molecules of host cells • To synthesize progeny viruses

12. Reproductive Cycles of Phages • Phages • Are the best understood of all viruses • Go through two alternative reproductive mechanisms: the lytic cycle and the lysogenic cycle

13. The Lytic Cycle • The lytic cycle • Is a phage reproductive cycle that culminates in the death of the host • Produces new phages and digests the host’s cell wall, releasing the progeny viruses

14. 1 Attachment. The T4 phage usesits tail fibers to bind to specificreceptor sites on the outer surface of an E. coli cell. 2 Entry of phage DNA and degradation of host DNA.The sheath of the tail contracts,injecting the phage DNA intothe cell and leaving an emptycapsid outside. The cell’sDNA is hydrolyzed. 5 Release. The phage directs productionof an enzyme that damages the bacterialcell wall, allowing fluid to enter. The cellswells and finally bursts, releasing 100 to 200 phage particles. Phage assembly 3 Synthesis of viral genomes and proteins. The phage DNAdirects production of phageproteins and copies of the phagegenome by host enzymes, usingcomponents within the cell. 4 Assembly. Three separate sets of proteinsself-assemble to form phage heads, tails,and tail fibers. The phage genome ispackaged inside the capsid as the head forms. Head Tail fibers Figure 18.6 Tails • The lytic cycle of phage T4, a virulent phage

15. The Lysogenic Cycle • The lysogenic cycle • Replicates the phage genome without destroying the host • Temperate phages • Are capable of using both the lytic and lysogenic cycles of reproduction

16. Phage DNA The phage attaches to a host cell and injects its DNA. Many cell divisions produce a large population of bacteria infected with the prophage. Phage DNA circularizes Phage Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Bacterial chromosome Lytic cycle Lysogenic cycle Certain factors determine whether The bacterium reproduces normally, copying the prophage and transmitting it to daughter cells. The cell lyses, releasing phages. Prophage Lytic cycle is induced Lysogenic cycle is entered or New phage DNA and proteins are synthesized and assembled into phages. Phage DNA integrates into the bacterial chromosome,becoming a prophage. Figure 18.7 • The lytic and lysogenic cycles of phage , a temperate phage

17. Reproductive Cycles of Animal Viruses • The nature of the genome • Is the basis for the common classification of animal viruses

18. Table 18.1 • Classes of animal viruses

19. Viral Envelopes • Many animal viruses • Have a membranous envelope • Viral glycoproteins on the envelope • Bind to specific receptor molecules on the surface of a host cell

20. Glycoproteins on the viral envelope bind to specific receptor molecules(not shown) on the host cell, promoting viral entry into the cell. Capsid RNA 2 1 Envelope (with glycoproteins) Capsid and viral genome enter cell 3 HOST CELL The viral genome (red) functions as a template forsynthesis of complementary RNA strands (pink) by a viral enzyme. Viral genome (RNA) Template 5 mRNA Complementary RNA strands also function as mRNA, which is translated into both capsid proteins (in the cytosol)and glycoproteins for the viral envelope (in the ER). New copies of viral genome RNA are made using complementary RNA strands as templates. 4 Capsid proteins ER Copy of genome (RNA) Glyco- proteins 6 Vesicles transport envelope glycoproteins to the plasma membrane. 7 New virus 8 A capsid assembles around each viral genome molecule. Figure 18.8 • The reproductive cycle of an enveloped RNA virus

21. RNA as Viral Genetic Material • The broadest variety of RNA genomes • Is found among the viruses that infect animals

22. Glycoprotein Viral envelope Capsid RNA(two identicalstrands) Reversetranscriptase Figure 18.9 • Retroviruses, such as HIV, use the enzyme reverse transcriptase • To copy their RNA genome into DNA, which can then be integrated into the host genome as a provirus

23. 1 Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. 2 The virus fuses with the cell’s plasma membrane. The capsid proteins are removed, releasing the viral proteins and RNA. Membrane of white blood cell HIV Reverse transcriptase catalyzes the synthesis ofa second DNA strand complementary to the first. 3 Reverse transcriptase HOST CELL Viral RNA 4 The double-stranded DNA is incorporated as a provirus into the cell’s DNA. RNA-DNAhybrid 0.25 µm HIV entering a cell DNA ChromosomalDNA NUCLEUS Provirus 5 Proviral genes are transcribed into RNA molecules, which serve as genomes for the next viral generation and as mRNAs for translation into viral proteins. RNA genomefor the nextviral generation mRNA 6 The viral proteins include capsid proteins and reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER). 7 Capsids are assembled around viral genomes and reverse transcriptase molecules. Vesicles transport the glycoproteins from the ER to the cell’s plasma membrane. 8 9 New viruses bud off from the host cell. Figure 18.10 New HIV leaving a cell • The reproductive cycle of HIV, a retrovirus

24. Evolution of Viruses • 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

25. Concept 18.2: Viruses, viroids, and prions are formidable pathogens in animals and plants • Diseases caused by viral infections • Affect humans, agricultural crops, and livestock worldwide

26. Viral Diseases in Animals • Viruses may damage or kill cells • By causing the release of hydrolytic enzymes from lysosomes • Some viruses cause infected cells • To produce toxins that lead to disease symptoms

27. Vaccines • Are harmless derivatives of pathogenic microbes that stimulate the immune system to mount defenses against the actual pathogen • Can prevent certain viral illnesses

28. Emerging Viruses • Emerging viruses • Are those that appear suddenly or suddenly come to the attention of medical scientists

29. (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) Young ballet students in Hong Kong wear face masks to protect themselves from the virus causing SARS. Figure 18.11 A, B • Severe acute respiratory syndrome (SARS) • Recently appeared in China

30. Outbreaks of “new” viral diseases in humans • Are usually caused by existing viruses that expand their host territory

31. Figure 18.12 Viral Diseases in Plants • More than 2,000 types of viral diseases of plants are known • Common symptoms of viral infection include • Spots on leaves and fruits, stunted growth, and damaged flowers or roots

32. Plant viruses spread disease in two major modes • Horizontal transmission, entering through damaged cell walls • Vertical transmission, inheriting the virus from a parent

33. Viroids and Prions: The Simplest Infectious Agents • Viroids • Are circular RNA molecules that infect plants and disrupt their growth

34. Originalprion Prion Many prions Normalprotein Newprion Figure 18.13 • Prions • Are slow-acting, virtually indestructible infectious proteins that cause brain diseases in mammals • Propagate by converting normal proteins into the prion version

35. (a) Regulation of enzyme activity (b) Regulation of enzyme production Precursor Feedback inhibition Enzyme 1 Gene 1 Regulation of gene expression Enzyme 2 Gene 2 Gene 3 Enzyme 3 – Gene 4 Enzyme 4 – Gene 5 Enzyme 5 Tryptophan Figure 18.20a, b • This metabolic control occurs on two levels • Adjusting the activity of metabolic enzymes already present • Regulating the genes encoding the metabolic enzymes

36. Operons: The Basic Concept • In bacteria, genes are often clustered into operons, composed of • An operator, an “on-off” switch • A promoter • Genes for metabolic enzymes

37. An operon • Is usually turned “on” • Can be switched off by a protein called a repressor

38. trp operon Promoter Promoter Genes of operon RNA polymerase Start codon Stop codon trpR trpD trpC trpB trpE trpA DNA Operator Regulatory gene 3 mRNA 5 mRNA 5 C E D B A Polypeptides that make up enzymes for tryptophan synthesis Inactiverepressor Protein (a) Tryptophan absent, repressor inactive, operon on. RNA polymerase attaches to the DNA at the promoter and transcribes the operon’s genes. Figure 18.21a • The trp operon: regulated synthesis of repressible enzymes

39. DNA No RNA made mRNA Active repressor Protein Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off. As tryptophan accumulates, it inhibits its own production by activating the repressor protein. Figure 18.21b

40. Repressible and Inducible Operons: Two Types of Negative Gene Regulation • In a repressible operon • Binding of a specific repressor protein to the operator shuts off transcription • In an inducible operon • Binding of an inducer to an innately inactive repressor inactivates the repressor and turns on transcription

41. Promoter Regulatorygene Operator DNA lacl lacZ NoRNAmade 3 RNApolymerase mRNA 5 Activerepressor Protein (a) Lactose absent, repressor active, operon off. The lac repressor is innately active, and inthe absence of lactose it switches off the operon by binding to the operator. Figure 18.22a • The lac operon: regulated synthesis of inducible enzymes

42. lac operon DNA lacl lacz lacY lacA RNApolymerase 3 mRNA 5 mRNA 5' mRNA 5 -Galactosidase Permease Transacetylase Protein Inactiverepressor Allolactose(inducer) (b) Lactose present, repressor inactive, operon on. Allolactose, an isomer of lactose, derepresses the operon by inactivating the repressor. In this way, the enzymes for lactose utilization are induced. Figure 18.22b

43. Inducible enzymes • Usually function in catabolic pathways • Repressible enzymes • Usually function in anabolic pathways

44. Regulation of both the trp and lac operons • Involves the negative control of genes, because the operons are switched off by the active form of the repressor protein

45. Positive Gene Regulation • Some operons are also subject to positive control • Via a stimulatory activator protein, such as catabolite activator protein (CAP)

46. Operator RNA polymerase can bindand transcribe Promoter DNA lacl lacZ CAP-binding site ActiveCAP cAMP Inactive lac repressor InactiveCAP (a) Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized.If glucose is scarce, the high level of cAMP activates CAP, and the lac operon produces large amounts of mRNA for the lactose pathway. Figure 18.23a • In E. coli, when glucose, a preferred food source, is scarce • The lac operon is activated by the binding of a regulatory protein, catabolite activator protein (CAP)

47. Promoter Operator DNA lacl lacZ CAP-binding site RNA polymerase can’t bind InactiveCAP Inactive lac repressor Lactose present, glucose present (cAMP level low): little lac mRNA synthesized.When glucose is present, cAMP is scarce, and CAP is unable to stimulate transcription. (b) Figure 18.23b • When glucose levels in an E. coli cell increase • CAP detaches from the lac operon, turning it off