Viruses

1. Viruses

2. Cause many infections of humans, animals, plants, and bacteria Cannot carry out any metabolic pathway Neither grow nor respond to the environment Cannot reproduce independently Obligate intracellular parasites Viruses

3. Cause most diseases that plague industrialized world Virus – miniscule, acellular, infectious agent having one or several pieces of either DNA or RNA No cytoplasmic membrane, cytosol, or organelles Have extracellular and intracellular state Characteristics of Viruses

4. Extracellular state Called virion Protein coat (capsid) surrounding nucleic acid Nucleic acid and capsid also called nucleocapsid Some have phospholipid envelope Outermost layer provides protection and recognition sites for host cells Characteristics of Viruses

5. Intracellular state Capsid removed Virus exists as nucleic acid Characteristics of Viruses

6. Type of genetic material they contain Kinds of cells they attack Size of virus Nature of capsid coat Shape of virus Presence or absence of envelope How Viruses Are Distinguished

7. Sizes of Viruses Figure 13.4

8. Show more variety in nature of their genomes than do cells May be DNA or RNA; never both Primary way scientists categorize and classify viruses Can be double stranded (ds) or single stranded (ss) so they are called dsDNA, ssDNA, dsRNA, or ssRNA Much smaller than even a gene of a host cell! Genetic Material of Viruses

9. Most are very host-specific: Most only infect particular kinds of host cells Due to affinity of viral surface proteins for complementary proteins on host cell surface A few are generalists – infect many kinds of cells in many different hosts Hosts of Viruses

10. Capsids – protein coats that provide protection for viral nucleic acid and means of attachment to host’s cells Capsid composed of proteinaceous subunits called capsomeres Some capsids composed of single type of capsomere; other composed of multiple types Capsid Morphology

11. Acquired from host cell during viral replication or release; envelope is portion of membrane system of host Composed of phospholipid bilayer and proteins; some proteins are virally-coded glycoproteins (spikes) Envelope’s proteins and glycoproteins often play role in host recognition The Viral Envelope

12. Dependent on host’s organelles and enzymes to produce new virions Replication cycle may or may not result in death of host cell Stages of lytic replication cycle Attachment Entry Synthesis Assembly Release Viral Replication

13. Chemical attraction Animal viruses do not have tails or tail fibers Have glycoprotein spikes or other attachment molecules that mediate attachment Attachment of Animal Viruses

14. Attachment

15. Entry/Penetration

16. Entry/Penetration

17. Each type of animal virus requires different strategy depending on its nucleic acid Must consider How mRNA is synthesized? What serves as template for nucleic acid replication? Synthesis of Animal Viruses

18. Genome Replication and Protein Synthesis Figure 13.13

19. Most DNA viruses assemble in and are released from nucleus into cytosol Most RNA viruses develop solely in cytoplasm Number of viruses produced and released depends on type of virus and size and initial health of host cell Enveloped viruses cause persistent infections Naked viruses released by exocytosis or may cause lysis and death of host cell Assembly and Release of Animal Viruses

20. Release Enveloped and Naked • Lysis • Exocytosis

21. Release • Enveloped • Budding

22. When animal viruses remain dormant in host cells May be prolonged for years with no viral activity, signs, or symptoms Some latent viruses do not become incorporated into host chromosome When provirus is incorporated into host DNA, condition is permanent; becomes permanent physical part of host’s chromosome Latency of Animal Viruses

23. Normally, animal’s genes dictate that some cells can no longer divide and those that can divide are prevented from unlimited division Genes for cell division “turned off” or genes that inhibit division “turned on” Neoplasia – uncontrolled cell division in multicellular animal; mass of neoplastic cells is tumor Benign vs. malignant tumors Metastasis Cancers The Role of Viruses in Cancer

24. Some carry copies of oncogenes as part of their genomes Some stimulate oncogenes already present in host Some interfere with tumor repression when they insert into host’s repressor gene Several DNA and RNA viruses are known to cause ~15% of human cancers Burkitt’s lymphoma Hodgkin’s disease Kaposi’s sarcoma Cervical cancer How Viruses Cause Cancer

25. Oncogene Theory Figure 13.15

26. In Whole Organisms Bacteria Plants and Animals Embryonated Chicken Eggs In Cell (Tissue Culture) Culturing Viruses in the Laboratory

27. Culturing Viruses in Embryonated Chicken Eggs Figure 13.17

28. Culturing Viruses in Cell (Tissue) Culture Figure 13.18

29. Prion • A prion is an infectious agent composed of protein in a misfoldedform. • This is in contrast to all other known infectious agents (virus/bacteria/fungus/parasite) which must contain nucleic acids (either DNA, RNA, or both). • All known prion diseases affect the structure of the brain or other neural tissue and all are currently untreatable and universally fatal. • Prions are responsible for "mad cow disease" in cattle and Creutzfeldt–Jakob disease (CJD) in humans.

30. Tertiary Structures of Prion proteins Figure 13.21

31. Virus Diseases • RNA Viruses • Picornaviridae: Polio, Hepatitis A, common cold • Coronaviridae: Common cold • Calicivirus: Stomach flu • Flaviviridae: Hepatitis C; West Nile • Retroviridae: AIDS • Togaviridae: German Measles • Paramyxovirus: Measles, mumps • Orthomyxovirus: Influenza • Rhabdoviridae: Rabies • Filoviridae: Hemorrhagic Fever • Reoviridae: Stomach flu • Prion Diseases • Mad Cow Disease • Creutzfeldt–Jakobdisease • Kuru • DNA Viruses • Poxviridae: Smallpox • Herpesviridae: Cold sores, chicken pox, mononucleosis • Hepadnoviridae: Hepatitis B • Papillomaviridae: Warts • Adenoviridae: Common cold, pink eye

32. Cattle Bovine spongiform encephalopathy (BSE; Mad Cow Disease) Humans Creutzfeldt–Jakob disease (CJD) Degenerative brain disease, incurable and fatal Can get it from use of contaminated brain products such as Human Growth Hormone obtained from the pituitary glands of persons who died from Creutzfeldt–Jakob Disease Kuru From cannibalism. Called Laughing Sickness; tremors are also classic symptoms Prion Diseases

33. All involve fatal neurological degeneration, deposition of fibrils in brain, and loss of brain matter Large vacuoles form in brain; characteristic spongy appearance Spongiform encephalopathies(causes holes in the brain) Only destroyed by incineration; not cooking or sterilization Prion Diseases

34. Kuru • Kuru is an incurable degenerative neurological disorder caused by a prion found in humans. • The term "kuru" derives from the Fore word "kuria/guria" ("to shake"), a reference to the body tremors that are a classic symptom of the disease • It is now widely accepted that Kuru was transmitted among members of the Fore tribe of Papua New Guinea via cannibalism. • It is also known among the Fore as the laughing sickness due to the pathologic bursts of laughter people would display when afflicted with the disease.

35. Fore Tribe of Papua, New Guinea

36. Classified based on the type of DNA they contain, the presence or absence of an envelope, size, and the host cells they attack Contain either double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) for their genome Double-stranded DNA viruses Poxviridae, Herpesviridae, Hepadnoviridae, Papillomaviridae, and Adenoviridae DNA Viruses

37. DNA Viruses • There are currently 21 families of viruses known to cause disease in humans. • There are six ds DNA families: • Three are enveloped • Poxviridae, Herpesviridae, and Hepadnaviridae • Three are non-enveloped • Papillomaviridae, Adenoviridae, Polyomaviridae • (the latter is not covered here) • There is one ss DNA family that infects humans: • They are non-enveloped • Parvoviridae (not covered here)

38. Virus Diseases • RNA Viruses • Picornaviridae: Polio, Hepatitis A, common cold • Coronaviridae: Common cold • Calicivirus: Stomach flu • Flaviviridae: Hepatitis C; West Nile • Retroviridae:AIDS • Togaviridae: German Measles • Paramyxovirus: Measles, mumps • Orthomyxovirus: Influenza • Rhabdoviridae: Rabies • Filoviridae: Hemorrhagic Fever • Reoviridae: Stomach flu • Prion Diseases • Mad Cow Disease • Creutzfeldt–Jakobdisease • Kuru • DNA Viruses • Poxviridae: Smallpox • Herpesviridae: Cold sores, chicken pox, mononucleosis • Hepadnoviridae: Hepatitis B • Papillomaviridae: Warts • Adenoviridae: Common cold, pink eye

39. DNA Viruses • Poxviridae • Smallpox • Herpesviridae • Cold sores, chicken pox, mononucleosis • Hepadnoviridae • Hepatitis B • Papillomaviridae • Warts • Adenoviridae • Common cold, pink eye

40. Double-stranded DNA viruses Have complex capsids and envelopes Largest viruses Infect many mammals Most animal poxviruses are species specific Unable to infect humans because they cannot attach to human cells Infection occurs primarily through the inhalation of viruses Close contact is necessary for infection by poxviruses Poxviridae

41. Smallpox and molluscumcontagiosum are the two main poxvirus diseases of humans Some diseases of animals can be transmitted to humans All poxviruses produce lesions that progress through a series of stages Poxviridae

42. Figure 24.2

43. In the genus Orthopoxvirus Commonly known as variola Exists in two forms Variola major causes severe disease that can result in death Variola minor causes a less severe disease with a much lower mortality rate Both forms infect internal organs and then move to the skin where they produce pox Scars result on the skin, especially on the face Smallpox

44. There are a number of factors that allowed eradication of smallpox Inexpensive, stable, and effective vaccine No animal reservoirs Obvious symptoms allow for quick diagnosis and quarantine Lack of asymptomatic cases Virus is only spread via close contact Smallpox

45. Smallpox as a Bioweapon • can be produced in large quantities • stable for storage and transport • stable in aerosolized form (up to 2 days) • high mortality • highly infectious (person-to-person spread) • most of the world has little to no immunity

46. Therapy/Prevention of Smallpox • Vaccination • vaccination stopped in 1979 (1972 in U.S.) • last case in U.S. 1949 • 2 million deaths Worldwide in 1967 • Vaccinia virus • leaves scar • Supportive therapy – no effective antiviral once infected

47. Caused by Molluscipoxvirus Spread by contact among infected children Sexually active adults can sometimes contract a genital form of the disease Skin disease characterized by smooth, waxy, tumor-like nodules on the face, trunk, and limbs Virus produces a weak immune response Causes neighboring cells to divide rapidly thus acting like a tumor-causing virus MolluscumContagiosum

48. Poxvirus infections also occur in animals Transmission of these poxviruses to humans require close contact with infected animals Infections of humans are usually mild Can result in pox and scars but usually little other damage Cowpox was used by Edward Jenner to immunize individuals against smallpox Other Poxvirus Infections

49. Rescued kitten infected girl with rare virus • A teenager in the Netherlands who rescued a drowning kitten from a ditch developed a large, blackened open wound on her wrist, which took multiple doctors several weeks to find its rare cause.

50. Rescued kitten infected girl with rare virus • The kitten that the girl rescued was sick and died the following day, and the 17-year-old developed a red wound on her wrist that blistered before turning black. She also developed painful red bumps on her arm, spanning from the wound on her wrist up to her armpit.