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Viruses, Viroids, and Prions

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1 Viruses, Viroids, and Prions
13 Viruses, Viroids, and Prions

2

3 General Characteristics of Viruses
Learning Objective 13-1 Differentiate a virus from a bacterium.

4 General Characteristics of Viruses
Obligatory intracellular parasites Require living host cells to multiply Contain DNA or RNA Contain a protein coat No ribosomes No ATP-generating mechanism

5 Table 13.1 Viruses and Bacteria Compared

6 Host Range The spectrum of host cells a virus can infect
Most viruses infect only specific types of cells in one host Determined by specific host attachment sites and cellular factors Bacteriophages—viruses that infect bacteria Range from 20 nm to 1000 nm in length

7 Figure 13.1 Virus sizes. 800 × 10 nm Bacteriophage M13 970 nm
Bacteriophages f2, MS2 24 nm Ebola virus Poliovirus 30 nm Rhinovirus 30 nm Adenovirus 90 nm 300 nm Chlamydia bacterium elementary body Rabies virus 170 × 70 nm E. coli bacterium 3000 × 1000 nm Prion 200 × 20 nm Human red blood cell 10,000 nm in diameter Bacteriophage T4 225 nm Tobacco mosaic virus 250 × 18 nm Plasma membrane of red blood cell 10 nm thick Viroid 300 × 10 nm Vaccinia virus 300 × 200 × 100 nm

8 Check Your Understanding
How could the small size of viruses have helped researchers detect viruses before the invention of the electron microscope? 13-1

9 Viral Structure Learning Objective
13-2 Describe the chemical and physical structure of both an enveloped and a nonenveloped virus.

10 Viral Structure Virion—complete, fully developed viral particle
Nucleic acid—DNA or RNA can be single- or double-stranded; linear or circular Capsid—protein coat made of capsomeres (subunits) Envelope—lipid, protein, and carbohydrate coating on some viruses Spikes—projections from outer surface

11 Nucleic acid Capsomere Capsid
Figure Morphology of a nonenveloped polyhedral virus. Nucleic acid Capsomere Capsid

12 Nucleic acid Capsomere Envelope Spikes
Figure Morphology of an enveloped helical virus. Nucleic acid Capsomere Envelope Spikes

13 General Morphology Helical viruses—hollow, cylindrical capsid
Polyhedral viruses—many-sided Enveloped viruses Complex viruses—complicated structures

14 Nucleic acid Capsomere Capsid
Figure Morphology of a helical virus. Nucleic acid Capsomere Capsid

15 Figure 13.5 Morphology of complex viruses.
65 nm Capsid (head) DNA Sheath Tail fiber Pin Baseplate A T-even bacteriophage Orthopoxvirus

16 Check Your Understanding
Diagram a nonenveloped polyhedral virus that has spikes. 13-2

17 Taxonomy of Viruses Learning Objectives 13-3 Define viral species.
13-4 Give an example of a family, genus, and common name for a virus.

18 Taxonomy of Viruses Genus names end in -virus
Family names end in -viridae Order names end in -ales Viral species: a group of viruses sharing the same genetic information and ecological niche (host) Descriptive common names are used for species Subspecies are designated by a number

19 Check Your Understanding
How does a virus species differ from a bacterial species? 13-3 Attach the proper endings to Papilloma- to show the family and genus that includes HPV, the cause of cervical cancer. 13-4

20 Isolation, Cultivation, and Identification of Viruses
Learning Objectives 13-5 Describe how bacteriophages are cultured Describe how animal viruses are cultured List three techniques used to identify viruses.

21 Growing Bacteriophages in the Laboratory
Viruses must be grown in living cells Bacteriophages are grown in bacteria Bacteriophages form plaques, which are clearings on a lawn of bacteria on the surface of agar Each plaque corresponds to a single virus; can be expressed as plaque-forming units (PFU)

22 Figure 13.6 Viral plaques formed by bacteriophages.

23 Growing Animal Viruses in the Laboratory
In living animals In embryonated eggs Virus injected into the egg Viral growth is signaled by changes or death of the embryo

24 Amniotic Chorioallantoic cavity membrane Shell Chorioallantoic
Figure Inoculation of an embryonated egg. Amniotic cavity Chorioallantoic membrane Shell Chorioallantoic membrane inoculation Air sac Amniotic inoculation Yolk sac Allantoic inoculation Shell membrane Yolk sac inoculation Albumin Allantoic cavity

25 Growing Animal Viruses in the Laboratory
In cell cultures Tissues are treated with enzymes to separate cells Virally infected cells are detected via their deterioration, known as the cytopathic effect (CPE) Continuous cell lines are used

26 Figure 13.8 Cell cultures. Normal cells Transformed cells
A tissue is treated with enzymes to separate the cells. Cells are suspended in culture medium. Normal cells or primary cells grow in a monolayer across the glass or plastic container. Transformed cells or continuous cell cultures do not grow in a monolayer.

27 Figure 13.9 The cytopathic effect of viruses.

28 Viral Identification Cytopathic effects Serological tests
Western blotting—reaction of the virus with antibodies Nucleic acids RFLPs PCR

29 Check Your Understanding
What is the plaque method? 13-5 Why are continuous cell lines of more practical use than primary cell lines for culturing viruses? 13-6 What tests could you use to identify influenza virus in a patient? 13-7

30 Viral Multiplication Learning Objectives
13-8 Describe the lytic cycle of T-even bacteriophages. 13-9 Describe the lysogenic cycle of bacteriophage lambda. 13-10 Compare and contrast the multiplication cycle of DNA- and RNA-containing animal viruses.

31 Viral Multiplication For a virus to multiply: One-step growth curve
It must invade a host cell It must take over the host's metabolic machinery One-step growth curve

32 Figure 13.10 A viral one-step growth curve.

33 Multiplication of Bacteriophages
Lytic cycle Phage causes lysis and death of the host cell Lysogenic cycle Phage DNA is incorporated in the host DNA Phage conversion Specialized transduction

34 Viral Replication: Virulent Bacteriophages
PLAY Animation: Viral Replication: Virulent Bacteriophages

35 Viral Replication: Temperate Bacteriophages
PLAY Animation: Viral Replication: Temperate Bacteriophages

36 T-Even Bacteriophages: The Lytic Cycle
Attachment: phage attaches by the tail fibers to the host cell Penetration: phage lysozyme opens the cell wall; tail sheath contracts to force the tail core and DNA into the cell Biosynthesis: production of phage DNA and proteins Maturation: assembly of phage particles Release: phage lysozyme breaks the cell wall

37 Figure 13.11 The lytic cycle of a T-even bacteriophage.
Bacterial cell wall Bacterial chromosome Capsid DNA Capsid (head) Sheath Attachment: Phage attaches to host cell. Tail fiber Tail Baseplate Pin Cell wall Plasma membrane Penetration: Phage penetrates host cell and injects its DNA. Sheath contracted Biosynthesis: Phage DNA directs synthesis of viral components by the host cell. Tail core Tail DNA Maturation: Viral components are assembled into virions. Capsid Release: Host cell lyses, and new virions are released. Tail fibers

38 Bacteriophage Lambda (λ): The Lysogenic Cycle
Lysogeny: phage remains latent Phage DNA incorporates into host cell DNA Inserted phage DNA is known as a prophage When the host cell replicates its chromosome, it also replicates prophage DNA Results in phage conversion—the host cell exhibits new properties

39 Figure 13.12 The lysogenic cycle of bacteriophage λ in E. coli.
Phage attaches to host cell and injects DNA. Occasionally, the prophage may excise from the bacterial chromosome by another recombination event, initiating a lytic cycle. Phage DNA (double-stranded) Bacterial chromosome Many cell divisions Lytic cycle Lysogenic cycle Cell lyses, releasing phage virions. Phage DNA circularizes and enters lytic cycle or lysogenic cycle. Lysogenic bacterium reproduces normally. Prophage OR New phage DNA and proteins are synthesized and assembled into virions. Phage DNA integrates within the bacterial chromosome by recombination, becoming a prophage.

40 Bacteriophage Lambda (λ): The Lysogenic Cycle
Specialized transduction Specific bacterial genes transferred to another bacterium via a phage Changes genetic properties of the bacteria

41 Figure 13.13 Specialized transduction.
Prophage gal gene Prophage exists in galactose-using host (containing the gal gene). Bacterial DNA Galactose- positive donor cell gal gene Phage genome excises, carrying with it the adjacent gal gene from the host. gal gene Phage matures and cell lyses, releasing phage carrying gal gene. Phage infects a cell that cannot utilize galactose (lacking gal gene). Galactose- negative recipient cell Along with the prophage, the bacterial gal gene becomes integrated into the new host's DNA. Lysogenic cell can now metabolize galactose. Galactose-positive recombinant cell

42 Transduction: Generalized Transduction
PLAY Animation: Transduction: Generalized Transduction

43 Transduction: Specialized Transduction
PLAY Animation: Transduction: Specialized Transduction

44 Check Your Understanding
How do bacteriophages get nucleotides and amino acids if they don't have any metabolic enzymes? 13-8 Vibrio cholerae produces toxin and is capable of causing cholera only when it is lysogenic. What does this mean? 13-9

45 Table 13.3 Bacteriophage and Animal Viral Multiplication Compared

46 Multiplication of Animal Viruses
Attachment: viruses attach to the cell membrane Entry by receptor-mediated endocytosis or fusion Uncoating by viral or host enzymes Biosynthesis: production of nucleic acid and proteins Maturation: nucleic acid and capsid proteins assemble Release by budding (enveloped viruses) or rupture

47 Entry of pig retrovirus by receptor-mediated endocytosis.
Figure The entry of viruses into host cells. Host plasma membrane proteins at site of receptor-mediated endocytosis Fusion of viral envelope and plasma membrane Entry of pig retrovirus by receptor-mediated endocytosis. Entry of herpesvirus by fusion.

48 Figure 13.20 Budding of an enveloped virus.
Viral capsid Host cell plasma membrane Viral protein Bud Bud Envelope Release by budding Lentivirus

49 Viral Replication: Overview
PLAY Animation: Viral Replication: Overview

50 Viral Replication: Animal Viruses
PLAY Animation: Viral Replication: Animal Viruses

51 The Biosynthesis of DNA Viruses
DNA viruses replicate their DNA in the nucleus of the host using viral enzymes Synthesize capsid in the cytoplasm using host cell enzymes

52 Figure 13.15 Replication of a DNA-Containing Animal Virus.
ATTACHMENT Virion attaches to host cell. A papovavirus is a typical DNA-containing virus that attacks animal cells. Papovavirus RELEASE Virions are released. DNA Host cell ENTRY and UNCOATING Virion enters cell, and its DNA is uncoated. Capsid MATURATION Virions mature. Nucleus Cytoplasm Capsid proteins Viral DNA Capsid proteins BIOSYNTHESIS Viral DNA is replicated, and some viral proteins are made. mRNA Late translation; capsid proteins are synthesized. A portion of viral DNA is transcribed, producing mRNA that encodes "early" viral proteins. KEY CONCEPTS Viral replication in animals generally follows these steps: attachment, entry, uncoating, biosynthesis of nucleic acids and proteins, maturation, and release. Knowledge of viral replication phases is important for drug development strategies, and for understanding disease pathology.

53 The Biosynthesis of DNA Viruses
Adenoviridae Double-stranded DNA, nonenveloped Respiratory infections in humans Tumors in animals

54 Figure 13.16a DNA-containing animal viruses.
Capsomere Mastadenovirus

55 The Biosynthesis of DNA Viruses
Poxviridae Double-stranded DNA, enveloped Cause skin lesions Vaccinia and smallpox viruses (Orthopoxvirus)

56 The Biosynthesis of DNA Viruses
Herpesviridae Double-stranded DNA, enveloped HHV-1 and HHV-2—Simplexvirus; cause cold sores HHV-3—Varicellovirus; causes chickenpox HHV-4—Lymphocryptovirus; causes mononucleosis HHV-5—Cytomegalovirus HHV-6 and HHV-7—Roseolovirus HHV-8—Rhadinovirus; causes Kaposi's sarcoma

57 Figure 13.16b DNA-containing animal viruses.
Capsomeres Simplexvirus

58 The Biosynthesis of DNA Viruses
Papovaviridae Double-stranded DNA, nonenveloped Papillomavirus Causes warts Can transform cells and cause cancer

59 The Biosynthesis of DNA Viruses
Hepadnaviridae Double-stranded DNA, enveloped Hepatitis B virus Use reverse transcriptase to make DNA from RNA

60 The Biosynthesis of RNA Viruses
Virus multiplies in the host cell's cytoplasm using RNA-dependent RNA polymerase ssRNA; + (sense) strand Viral RNA serves as mRNA for protein synthesis ssRNA; – (antisense) strand Viral RNA is transcribed to a + strand to serve as mRNA for protein synthesis dsRNA—double-stranded RNA

61 Figure 13.17a Pathways of multiplication used by various RNA-containing viruses.
Attachment Capsid Nucleus RNA Host cell Cytoplasm Entry and uncoating Maturation and release Translation and synthesis of viral proteins RNA replication by viral RNA– dependent RNA polymerase – strand is transcribed from + viral genome. Uncoating releases viral RNA and proteins. KEY Capsid protein Viral genome (RNA) Viral protein + or sense strand of viral genome – or antisense strand of viral genome + strand ss = single-stranded mRNA is transcribed from the – strand. ssRNA; + or sense strand; Picornaviridae ds = double-stranded

62 Figure 13.17b Pathways of multiplication used by various RNA-containing viruses.
Attachment Capsid Nucleus RNA Host cell Cytoplasm Entry and uncoating Maturation and release Translation and synthesis of viral proteins RNA replication by viral RNA– dependent RNA polymerase The + strand (mRNA) must first be transcribed from the – viral genome before proteins can be synthesized. Uncoating releases viral RNA and proteins. Capsid protein KEY Viral genome (RNA) Viral protein + or sense strand of viral genome – or antisense strand of viral genome ss = single-stranded – strands are incorporated into capsid ssRNA; – or antisense strand; Rhabdoviridae Additional – strands are transcribed from mRNA. ds = double-stranded

63 Figure 13.17c Pathways of multiplication used by various RNA-containing viruses.
Attachment Capsid Nucleus RNA Host cell Cytoplasm Entry and uncoating Maturation and release Translation and synthesis of viral proteins RNA replication by viral RNA– dependent RNA polymerase RNA polymerase initiates production of – strands. The mRNA and – strands form the dsRNA that is incorporated as new viral genome. mRNA is produced inside the capsid and released into the cytoplasm of the host. Uncoating releases viral RNA and proteins. KEY Viral genome (RNA) Viral protein + or sense strand of viral genome – or antisense strand of viral genome ss = single-stranded Capsid proteins and RNA- dependent RNA polymerase dsRNA; + or sense strand with – or antisense strand; Reoviridae ds = double-stranded

64 The Biosynthesis of RNA Viruses
Picornaviridae Single-stranded RNA, + strand, nonenveloped Enterovirus Poliovirus and coxsackievirus Rhinovirus Common cold Hepatitis A virus

65 The Biosynthesis of RNA Viruses
Togaviridae Single-stranded RNA, + strand, enveloped Alphavirus Transmitted by arthropods; includes chikungunya Rubivirus Rubella

66 The Biosynthesis of RNA Viruses
Rhabdoviridae Single-stranded RNA, − strand, one RNA strand Lyssavirus Rabies Numerous animal diseases

67 The Biosynthesis of RNA Viruses
Reoviridae Double-stranded RNA, nonenveloped Reovirus (respiratory enteric orphan) Rotavirus (mild respiratory infections and gastroenteritis)

68 Biosynthesis of RNA Viruses That Use DNA
Single-stranded RNA, produce DNA Use reverse transcriptase to produce DNA from the viral genome Viral DNA integrates into the host chromosome as a provirus Retroviridae Lentivirus (HIV) Oncoviruses

69 Figure 13.19 Multiplication and inheritance processes of the Retroviridae.
Reverse transcriptase Capsid Envelope Virus Two identical + strands of RNA Host cell Retrovirus enters by fusion between attachment spikes and the host cell receptors. Uncoating releases the two viral RNA strands and the viral enzymes reverse transcriptase, integrase, and protease. Mature retrovirus leaves the host cell, acquiring an envelope and attachment spikes as it buds out. DNA of one of the host cell's chromosomes Viral enzymes Viral DNA Viral RNA Reverse transcriptase copies viral RNA to produce double- stranded DNA. Viral proteins are processed by viral protease; some of the viral proteins are moved to the host plasma membrane. Provirus Identical strands of RNA Viral proteins The new viral DNA is transported into the host cell's nucleus, where it's integrated into a host cell chromosome as a provirus by viral integrase. The provirus may be replicated when the host cell replicates. RNA Transcription of the provirus may also occur, producing RNA for new retrovirus genomes and RNA that encodes the retrovirus capsid, enzymes, and envelope proteins.

70 Table 13.2 Families of Viruses That Affect Humans (1 of 4)

71 Table 13.2 Families of Viruses That Affect Humans (2 of 4)

72 Table 13.2 Families of Viruses That Affect Humans (3 of 4)

73 Table 13.2 Families of Viruses That Affect Humans (4 of 4)

74 Check Your Understanding
Describe the principal events of attachment, entry, uncoating, biosynthesis, maturation, and release of an enveloped DNA-containing virus

75 Viruses and Cancer Learning Objectives
13-11 Define oncogene and transformed cell. 13-12 Discuss the relationship between DNA- and RNA-containing viruses and cancer.

76 Viruses and Cancer Several types of cancer are caused by viruses
May develop long after a viral infection Cancers caused by viruses are not contagious Sarcoma: cancer of connective tissue Adenocarcinomas: cancers of glandular epithelial tissue

77 The Transformation of Normal Cells into Tumor Cells
Oncogenes transform normal cells into cancerous cells Oncogenic viruses become integrated into the host cell's DNA and induce tumors A transformed cell harbors a tumor-specific transplant antigen (TSTA) on the surface and a T antigen in the nucleus

78 DNA Oncogenic Viruses Adenoviridae Herpesviridae Poxviridae
Epstein-Barr virus Poxviridae Papovaviridae Human papillomavirus Hepadnaviridae Hepatitis B virus

79 RNA Oncogenic Viruses Retroviridae
Viral RNA is transcribed to DNA (using reverse transcriptase), which can integrate into host DNA HTLV-1 and HTLV-2 cause adult T cell leukemia and lymphoma

80 Check Your Understanding
What is a provirus? 13-11 How can an RNA virus cause cancer if it doesn't have DNA to insert into a cell's genome? 13-12

81 Latent Viral Infections and Persistent Viral Infections
Learning Objectives Provide an example of a latent viral infection Differentiate persistent viral infections from latent viral infections.

82 Latent Viral Infections and Persistent Viral Infections
Latent virus remains in asymptomatic host cell for long periods May reactivate due to changes in immunity Cold sores, shingles A persistent viral infection occurs gradually over a long period; is generally fatal Subacute sclerosing panencephalitis (measles virus)

83 Acute infection Latent infection Persistent infection
Figure Latent and persistent viral infections. Acute infection Latent infection Persistent infection

84 Table 13.5 Examples of Latent and Persistent Viral Infections in Humans

85 Check Your Understanding
Is shingles a persistent or latent infection? 13-13, 13-14

86 Prions Learning Objective
13-15 Discuss how a protein can be infectious.

87 Prions Proteinaceous infectious particles
Inherited and transmissible by ingestion, transplant, and surgical instruments Spongiform encephalopathies "Mad cow disease" Creutzfeldt-Jakob disease (CJD) Gerstmann-Sträussler-Scheinker syndrome Fatal familial insomnia Sheep scrapie

88 Prions PrPC: normal cellular prion protein, on the cell surface
PrPSc: scrapie protein; accumulates in brain cells, forming plaques

89 Prions: Overview PLAY Animation: Prions: Overview

90 Prions: Characteristics
PLAY Animation: Prions: Characteristics

91 Prions: Diseases PLAY Animation: Prions: Diseases

92 Figure 13.22 How a protein can be infectious.
PrPSc PrPc PrPc produced by cells is secreted to the cell surface. PrPSc may be acquired or produced by an altered PrPc gene. PrPSc reacts with PrPc on the cell surface. PrPSc converts the PrPc to PrPSc. Lysosome Endosome PrPSc accumulates in endosomes. PrPSc continues to accumulate as the endosome contents are transferred to lysosomes. The result is cell death. The new PrPSc converts more PrPc. The new PrPSc is taken in, possibly by receptor- mediated endocytosis.

93 Plant Viruses and Viroids
Learning Objectives 13-16 Differentiate virus, viroid, and prion. 13-17 Describe the lytic cycle for a plant virus.

94 Plant Viruses and Viroids
Plant viruses: enter through wounds or via insects Plant cells are generally protected from disease by an impermeable cell wall Viroids: short pieces of naked RNA Cause potato spindle tuber disease

95 Figure 13.23 Linear and circular potato spindle tuber viroid (PSTV).

96 Table 13.6 Classification of Some Major Plant Viruses

97 Check Your Understanding
Contrast viroids and prions, and for each name a disease it causes , 13-16 How do plant viruses enter host cells? 13-17


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