1. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Chapter 19 Viruses

2. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Overview: A Borrowed Life Viruses called bacteriophages can infect and set in motion a genetic takeover of bacteria, such as Escherichia coli Viruses lead “a kind of borrowed life” between life- forms and chemicals The origins of molecular biology lie in early studies of viruses that infect bacteria Bacteriophages infecting E. coli.

3. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Concept 19.1: A virus consists of a nucleic acid surrounded by a protein coat Viruses were detected indirectly long before they were actually seen Their discovery dates back to the end of the 19 th century.

4. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings The Discovery of Viruses: Scientific Inquiry Tobacco mosaic disease stunts growth of tobacco plants and gives their leaves a mosaic coloration In the late 1800s, researchers hypothesized that a particle smaller than bacteria caused the disease In 1935, Wendell Stanley confirmed this hypothesis by crystallizing the infectious particle, now known as tobacco mosaic virus (TMV) (living things cannot be crystalized)

5. Fig. 19-2 RESULTS 12 3 Extracted sap from tobacco plant with tobacco mosaic disease Passed sap through a porcelain filter known to trap bacteria Rubbed filtered sap on healthy tobacco plants 4 Healthy plants became infected The infectious agent could not be a bacterium because could pass through the filter. It also must be reproducing because its ability to cause disease was undiluted after several transfers from plant to plant.

6. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Structure of Viruses The word “Virus” is Latin for “poison”. Viruses are not cells Viruses are very small infectious particles consisting of nucleic acid enclosed in a protein coat and, in some cases, a membranous envelope The smallest viruses are smaller than ribosomes and must be viewed with an electron microscope.

7. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Viral Genomes Viral genomes may consist of either – Double- or single-stranded DNA, or – Double- or single-stranded RNA Depending on its type of nucleic acid, a virus is called a DNA virus or an RNA virus

8. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Capsids and Envelopes A capsid is the protein shell that encloses the viral genome Capsids are built from protein subunits called capsomeres A capsid can have various structures – Rod (helical-shape) – Icosohedral

9. Fig. 19-3 RNA Capsomere of capsid DNA Glycoprotein 18  250 nm 70–90 nm (diameter) Glycoproteins 80–200 nm (diameter) 80  225 nm Membranous envelope RNA Capsid Head DNA Tail sheath Tail fiber 50 nm 20 nm (a) Tobacco mosaic virus (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4

10. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Some viruses have membranous envelopes that help them infect hosts These viral envelopes surround the capsids of influenza viruses and many other viruses found in animals Viral envelopes, which are derived from the host cell’s membrane, contain a combination of viral and host cell molecules

11. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Bacteriophages, also called phages, are viruses that infect bacteria They have the most complex capsids found among viruses Phages have an elongated capsid head that encloses their DNA A protein tail piece attaches the phage to the host and injects the phage DNA inside

12. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Concept 19.2: Viruses reproduce only in host cells Viruses are obligate intracellular parasites, which means they can reproduce only within a host cell Each virus has a host range, a limited number of host cells that it can infect – Identify host’s by a “lock and key” fit between viral surface proteins and cell receptors

13. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings General Features of Viral Reproductive Cycles Once a viral genome has entered a cell, the cell begins to manufacture viral proteins The virus makes use of host enzymes, ribosomes, tRNAs, amino acids, ATP, and other molecules Viral nucleic acid molecules and capsomeres spontaneously self-assemble into new viruses Animation: Simplified Viral Reproductive Cycle Animation: Simplified Viral Reproductive Cycle

14. Transcription and manufacture of capsid proteins Self-assembly of new virus particles and their exit from the cell Entry and uncoating Fig. 19-4 VIRUS 1 2 3 DNA Capsid 4 Replication HOST CELL Viral DNA mRNA Capsid proteins Viral DNA 1. Virus enters and is uncoated, releasing viral DNA and capsid proteins 2.Host enzymes replicate the viral genome. 3. Host enzymes transcribe the viral genome into viral mRNA, which host ribosomes use to make more capsid proteins. 4.Viral genomes and capsid proteins self-assemble into new viruses which exit the cell.

15. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Reproductive Cycles of Phages Phages are the best understood of all viruses Phages have two reproductive mechanisms: the lytic cycle and the lysogenic cycle

16. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings The Lytic Cycle The lytic cycle is a phage reproductive cycle that culminates in the death of the host cell The lytic cycle produces new phages and digests the host’s cell wall, releasing the progeny viruses A phage that reproduces only by the lytic cycle is called a virulent phage Bacteria have defenses against phages, including restriction enzymes that recognize and cut up certain phage DNA Animation: Phage T4 Lytic Cycle Animation: Phage T4 Lytic Cycle

17. Fig. 19-5-1 Attachment 1 The T4 bacteriophage is a very virulent phage and is often used to illustrate the lytic cycle. “Lytic” refers to the last stage of infection in which The bacterium lyses (breaks open)

18. Fig. 19-5-2 Entry of phage DNA and degradation of host DNA Attachment 1 2

19. Fig. 19-5-3 Synthesis of viral genomes and proteins Entry of phage DNA and degradation of host DNA Attachment 1 2 3

20. Fig. 19-5-4 Phage assembly Assembly Synthesis of viral genomes and proteins Entry of phage DNA and degradation of host DNA Attachment 1 2 4 HeadTailTail fibers 3

21. Fig. 19-5-5 Phage assembly HeadTailTail fibers Assembly Release Synthesis of viral genomes and proteins Entry of phage DNA and degradation of host DNA Attachment 1 2 4 5 3

22. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings The Lysogenic Cycle The lysogenic cycle replicates the phage genome without destroying the host The viral DNA molecule is incorporated into the host cell’s chromosome This integrated viral DNA is known as a prophage Every time the host divides, it copies the phage DNA and passes the copies to daughter cells Animation: Phage Lambda Lysogenic and Lytic Cycles Animation: Phage Lambda Lysogenic and Lytic Cycles

23. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings An environmental signal can trigger the virus genome to exit the bacterial chromosome and switch to the lytic mode Phages that use both the lytic and lysogenic cycles are called temperate phages The lambda bacteriophage is a temperate phage that is commonly used to illustrate the lysogenic cycle (“lysogenic” refers to their ability to generate the active phages that can lyse the bacterium)

24. Fig. 19-6 Phage DNA Phage The phage injects its DNA. Bacterial chromosome Phage DNA circularizes. Daughter cell with prophage Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Cell divisions produce population of bacteria infected with the prophage. The cell lyses, releasing phages. Lytic cycle is induced or Lysogenic cycle is entered Lysogenic cycle Prophage The bacterium reproduces, copying the prophage and transmitting it to daughter cells. Phage DNA integrates into the bacterial chromosome, becoming a prophage. New phage DNA and proteins are synthesized and assembled into phages. Phage λ (lambda) has a single, short tail fiber.

25. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Reproductive Cycles of Animal Viruses There are two key variables used to classify viruses that infect animals: – DNA or RNA? – Single-stranded or double-stranded?

26. Table 19-1a

27. Table 19-1b

28. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Viral Envelopes Many viruses that infect animals have a membranous envelope Viral glycoproteins on the envelope bind to specific receptor molecules on the surface of a host cell Some viral envelopes are formed from the host cell’s plasma membrane as the viral capsids exit

29. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Other viral membranes form from the host’s nuclear envelope and are then replaced by an envelope made from Golgi apparatus membrane The reproductive cycle of many enveloped viruses does not necessarily kill the host cell, in contrast to the lytic cycles of phages.

30. Fig. 19-7 Capsid RNA Envelope (with glycoproteins) Capsid and viral genome enter the cell HOST CELL Viral genome (RNA) Template mRNA ER Glyco- proteins Capsid proteins Copy of genome (RNA) New virus 1.Glycoproteins on virus bind to receptors on cell (not shown) 2. Capsid and RNA enter cell: Capsid is digested by cellular enzymes. 3. The viral genome (red) is a template for synthesis of complementary RNA strands (pink) by a viral enzyme which is packaged inside the viral capsid 4.New copies of viral genome RNA are made using complementary RNA strands as templates 5.Complementary RNA strands also act as mRNA, which is translated into both capsid proteins (in cytosol) and glycoproteins (in ER) 6.Vesicles transport envelope glycoproteins to the plasma membrane 7.Capsid assembles around viral genome 8.Virus buds from the cell, its envelope studded with viral glycoproteins embedded in membrane derived from the host cell.

31. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings RNA as Viral Genetic Material The broadest variety of RNA genomes is found in viruses that infect animals Retroviruses use reverse transcriptase to copy their RNA genome into DNA. This flow of information (RNA DNA) is backwards: hence the name “retro” virus. HIV (human immunodeficiency virus) is the retrovirus that causes AIDS (acquired immunodeficiency syndrome)

32. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings The viral DNA that is integrated into the host genome is called a provirus Unlike a prophage, a provirus remains a permanent resident of the host cell The host’s RNA polymerase transcribes the proviral DNA into RNA molecules The RNA molecules function both as mRNA for synthesis of viral proteins and as genomes for new virus particles released from the cell Animation: HIV Reproductive Cycle Animation: HIV Reproductive Cycle

33. Fig. 19-8a Glycoprotein Reverse transcriptase HIV RNA (two identical strands) Capsid Viral envelope HOST CELL Reverse transcriptase Viral RNA RNA-DNA hybrid DNA NUCLEUS Provirus Chromosomal DNA RNA genome for the next viral generation mRNA New virus 2. Virus fuses w/ plasma membrane. Capsid proteins are removed, releasing viral proteins and RNA 1.HIV is an enveloped virus w/ 2 identical strands of RNA and 2 molecules of reverse transcriptase. 3. Reverse transcriptase synthesizes a DNA strand complementary to the viral RNA 4.Reverse transcriptase synthesizes a second DNA strand complementary to the first. 5. Dbl stranded DNA is incorporated as a provirus into cell’s DNA. 6. Proviral genes transcribed into RNA 7. Viral proteins include capsid proteins and reverse transcriptase (made in cytosol) and envelope glycoproteins (made in ER) 8. Vesicles transport glycoproteins to plasma membrane 9.Capsids assemble around viral genomes and reverse transcriptase. 10. New viruses bud from cell **Note: The provirus never leaves the cell (unlike prophages)

34. Fig. 19-8b HIV Membrane of white blood cell HIV entering a cell 0.25 µm New HIV leaving a cell

35. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Evolution of Viruses Viruses do not fit our definition of living organisms Since viruses can reproduce only within cells, they probably evolved as bits of cellular nucleic acid Candidates for the source of viral genomes are plasmids, circular DNA in bacteria and yeasts, and transposons, small mobile DNA segments Plasmids, transposons, and viruses are all mobile genetic elements

36. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Mimivirus, a double-stranded DNA virus, is the largest virus yet discovered (“mimi” stands for mimicking microbe..because this virus is the size of a small bacterium) There is controversy about whether this virus evolved before or after cells

37. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Concept 19.3: Viruses, viroids, and prions are formidable pathogens in animals and plants Diseases caused by viral infections affect humans, agricultural crops, and livestock worldwide Smaller, less complex entities called viroids and prions also cause disease in plants and animals, respectively

38. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Viroids and Prions: The Simplest Infectious Agents Viroids 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 propagate by converting normal proteins into the prion version Scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob disease in humans are all caused by prions

39. Fig. 19-11 Prion Normal protein Original prion New prion Aggregates of prions

40. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Viral Diseases in Animals A viral infection can produce symptoms by several different methods. – 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 – Others have envelope proteins that are toxic The level of damage done often depends on the ability of the infected cells to regenerate – We recover from colds because respiratory cells regenerate. – Damage from polio virus is permanent because nerve cells do not regenerate.

41. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Vaccines are harmless derivatives of pathogenic microbes that stimulate the immune system to mount defenses against the actual pathogen Vaccines can prevent certain viral illnesses Viral infections cannot be treated by antibiotics Antiviral drugs can help to treat, though not cure, viral infections. Most antiviral drugs are designed to interfere with the enzymes that synthesize viral DNA or those that are required for the assembly of the virus.

42. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Emerging Viruses Emerging viruses are those that appear suddenly or suddenly come to the attention of scientists – Ex: HIV, Ebola, West Nile and most recently SARS – Severe acute respiratory syndrome (SARS) recently appeared in China (2002) Outbreaks of “new” viral diseases in humans are usually caused by existing viruses that expand their host territory

43. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings – Flu epidemics are caused by new strains of influenza virus to which people have little immunity – Viral diseases in a small isolated population can emerge and become global – New viral diseases can emerge when viruses spread from animals to humans – Viral strains that jump species can exchange genetic information with other viruses to which humans have no immunity

44. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings – These strains can cause pandemics, global epidemics – The “avian flu” is a virus that recently appeared in humans and originated in wild birds

45. Fig. 19-9a (a) The 1918 flu pandemic (Spanish Flu: H1N1)

46. Fig. 19-9b (b) Influenza A H5N1 virus (green) 0.5 µm (Hong Kong Flu: 1997)

47. Fig. 19-9c (c) Vaccinating ducks: to prevent spread of H5N1

48. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Viral Diseases in Plants More than 2,000 types of viral diseases of plants are known and cause spots on leaves and fruits, stunted growth, and damaged flowers or roots Most plant viruses have an RNA genome

49. Fig. 19-10 Viral infections cause the irregular brown patches on tomatoes, black blotching on squash, and streaking in tulips due to redistribution of pigment granules.

50. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings Plant viruses spread disease in two major modes: – Horizontal transmission, entering through damaged cell walls – Vertical transmission, inheriting the virus from a parent

51. Fig. 19-UN1 Phage DNA Bacterial chromosome The phage attaches to a host cell and injects its DNA Prophage Lysogenic cycle Temperate phage only Genome integrates into bacterial chromosome as prophage, which (1) is replicated and passed on to daughter cells and (2) can be induced to leave the chromosome and initiate a lytic cycle Lytic cycle Virulent or temperate phage Destruction of host DNA Production of new phages Lysis of host cell causes release of progeny phages

52. Fig. 19-UN2 Time A B Number of bacteria Number of viruses

53. Fig. 19-UN3

54. Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings You should now be able to: 1.Explain how capsids and envelopes are formed 2.Distinguish between the lytic and lysogenic reproductive cycles 3.Explain why viruses are obligate intracellular parasites 4.Describe the reproductive cycle of an HIV retrovirus 5.Describe three processes that lead to the emergence of new diseases 6.Describe viroids and prions