Viruses

1. Viruses Viruses Infectious agents acting INSIDE cells What are they? How do they work? Where do they come from? And… What good are they?

2. Key Concepts • A virus has a genome but can reproduce only within a host cell • Viruses, viroids, and prions are formidable pathogens in animals and plants

3. Viruses: Make a Living by Hijacking Cells • Not living organisms; lack some attributes of life. • Are infectious particles, can’t replicate independently. • Not cells and don’t carry out metabolism • Made of RNA or DNA usually enclosed in protein coat (viroids lack protein coat).

4. Viruses • Consist of • nucleic acid (dsDNA, ssRNA, dsRNA) and • protein coat = capsid. • Viral envelopes –in some allow them to infect host more efficiently – don’t lyse cell when new viruses are made • Bacteriophage – bacterial viruses

5. Protein coat (capsid) takes many shapes. DNA or RNA is always within the capsid

6. Some viruses have an envelope to cover them! Envelope – came from host’s cell membrane when virus budded out of host

7. Some VIRUSES have no envelope – they’re naked! HERE IS A virus THAT INFECTS BACTERIA – It is called a bacteriophage. Some viruses are naked!They have no envelope

8. Adenovirus Influenza virus Causes colds Causes the flu Photographer: Sebastian Kaulitzki | Agency: Dreamstime.com foxnews.com

9. How Big are viruses? Polio virus = 20 nanometers 20nm 1 nm – 0ne billionth of a meter! 3000 polio viruses fit across the diameter of a period at the end of a sentence in your book.

10. Viruses can’t reproduce on their own • They must invade a cell. • Once inside a cell, they cause the cell to make more viruses instead of their usual proteins. • They are intracellular obligate parasites – they can’t do anything on their own.

11. Viral Life Cycles – Lytic

12. 1 1 5 The lytic cycle demonstrates the steps that a virus takes in order to take over a cell. The steps are: • Attachment • Injection • Replication • Assembly • Lysis 2 4 3

14. Sometimes the virus doesn’t kill the cell right away and it becomes part of the cell’s genes. If this happens, the virus DNA becomes a provirus and can become activated at any time (like a time bomb).(prophage in bacteria cells) In the meantime, the provirus is passed on to all the offspring of that cell …. Maybe for many generations.

15. Viral Life Cycles - Lysogenic • Virus binds receptor site and injects nucleic acid. • Viral nucleic acid is incorporated into cells genome (crossing over) = prophage / provirus. • Every time cell divides it copies viral DNA as its own. • At some point, viral DNA leaves chromosome and enters lytic cycle.

17. When were viruses discovered? Viruses have apparently always been around. However, it wasn’t until 1897 that a Dutch scientist named Beijerinck called an invisible agent that was smaller than bacteria a virus (Latin for poison). He was studying tobacco leaves that had been infected with what we now know as tobacco mosaic virus.

18. Classification of Viruses By Shapeby Host typeby function Animal viruses Retroviruses attack a certain way. DNA viruses attack another way. Plant viruses

19. How do Viruses Attach to Host cell? • Viral protein interacts w/ host cell surface receptor. • Specificity of attachment allow viruses to infect one species but not another . This is why we don’t get the same diseases as our pets! • May attach to all host cells or just on certain cell type(s): • Polio  digestive tract – then moves to bloodstream and in some cases nerve cells • Rhinoviruses/Influenza  respiratory tract cells • Chicken Pox and Herpes viruses  skin and nerve cells • HIV  Immune system and brain

20. Acute Infections – = short in duration with rapid recovery • Virions (virus particles) usually remain localized and symptoms are typically short-lived.  • The infected host cells will die upon release of new virions, resulting in cell and tissue damage.  • The Host's defense mechanisms will likely eliminate the virus over a period of several  days or months. -often results in the host organism's immunity to future infection. • Examples of acute infections include measles, mumps, and influenza (the flu).  

21. Persistent Infections = viruses are continually present in the body Types • Late complications following an acute infection • Latent • Chronic • Slow

22. Persistent Infections • Late Complications following a viral infection: • Often persistent infections are actually the result of an acute infection.  • Ex: measles exhibits short infectious and disease phases, yet late complications in one in 300,000 individuals results in a fatal brain disorder (Subacute Sclerosing Panecephalitis (SSPE).  The new condition is the result of a defective viral  replication with brain cells.  • When present, SSPE usually occurs within 10 years of having the measles. • Progressive encephalitis can follow rubella infection

23. Persistent Infections cont’d: Latent infections • actual viruses cannot be detected until reactivation of the disease occurs • "latent" because they exhibit a long non-infectious stage between the original disease and the subsequent disease.  • Chicken pox and the shingles, both of which are caused by the same virus: Varicella-zoster virus.  Shingles or "zoster" appears after the virus becomes reactivated by unknown circumstances. • Herpes virus (both herpes simplex type 1 and 2)  is another ex. of a latent virus

24. Persistent Infections cont’d: • Continuous "chronic" infection follows a relatively brief disease stage.  • virus can be demonstrated in the body at all times • Examples of chronic infections include hepatitis B and C.  • Initial symptoms may include nausea, fever, and jaundice; however, the patient typically recovers but remains infectious.  • Over time the disease slowly manifests as hepatitis, cirrhosis of the liver, or cancer. 

25. SLOW Infections • infectious agents gradually increase in number over a very long period of time during which no significant symptoms are seen. (Not the same as Chronic) • Examples include HIV/AIDS, and prion diseases (even though they are not viral)

26. Remember this?? • DNA  RNA  Protein in nucleus nucleuscytoplasm cytoplasm ^ ^ Transcription Translation

27. RNA Viruses Ex = influenza, polio, HIV • Three types of replication • 1. RNA of virus is used directly as an mRNA encodes all enzymes and proteins required. • 2. Contain enzyme that copies viral RNA into a complementary strand that then acts as mRNA • The most famous example of RdRP is the Polio virus. • Also influenza 1,2,and 3 (RdRP =RNA dependent RNA Polymerase) • 3. Retroviruses – are packaged w/ enzyme Reverse Transcriptase that transcribes DNA from an RNA template so they can infect animal cells. HIV = human immunodeficiency virus

28. On Retroviruses: The Violoist’s Thumb by Sean Kean “They show no respect for the Maginot Line we’d prefer to draw between ‘their’ DNA and ‘our’ DNA.” Why do some viruses concvert RNA DNA after infecting cells: “DNA is sturdier, more enduring. Once these retroviruses  so named because they run the DNA RNA  Protein dogma backward – weave themselves into a cell’s DNA, the cell will faithfully copy the virus genes so long as they both shall live”

29. Retroviruses RNA viruses When infecting a cell, these viruses have to transcribe the RNA to DNA before the viral code can be read. This requires an enzyme, reverse transcriptase, to Change RNA to DNA then the viral code can be added to the cell’s DNA. Once part of the cell’s DNA, the viral code can cause the cell to make more viruses.

30. HIV IS A RETROVIRUS Gp120 & gp41 envelope

31. HOW HIV GETS INTO A CELL

32. HIV infecting a T cell HIV IN A CELL AND BUDDING OUT OF A CELL

33. HIV LIFE CYCLE HHMI Animation http://www.hhmi.org/biointeractive/media/hiv_life_cycle-lg.mov

34. Ways to get HIV At birth from mother Unprotected sex Dirty needles Blood transfusions

35. Y Y Y Y Y Y Y antibodies Y Y Y Y Immune response pathogen invasionantigenexposure skin skin free antigens in blood antigens on infected cells macrophages (APC) humoral response cellular response helperT cells B cells T cells plasmaB cells memoryB cells memoryT cells cytotoxicT cells

36. HIV/AIDS • Chronic attack on Helper T-cells of the immune system from initial acute infection (when patient has flu-like symptoms) until full blown immune deficiency which appear many years later • HIV remains localized in lymph nodes for years until Helper T-cells are depleted there, then moves into blood where its T-cell numbers drop and immune function is debilitated. • Rapid mutation –fastest known among the viruses! so fast that each variety cannot be characterized • Mutation is so great that vaccines cannot be made of noninfectious viruses – even killed virus, for fear that one may live or a mutation will make the virus active

37. T-cell count as disease progresses

38. HIV kills off Helper T-Cells • T-cells are a crucial type of immune cell . • HIV infections target these cells – specifically CD4 “Helper”T-cells • Many Helper T-cells self destruct – apoptosis – see article 2010 article:http://www.biologynews.net/archives/2010/11/26/deciphering_how_cd4_t_cells_die_during_hiv_infection.html

39. By 2020 – predictions are that… • HIV/AIDS will kill more people than any other disease outbreak in history. • As many as 1 billion/yr (1 in 6 people) • 70% cases occur in Africa – but it is not limited to 3rd world countries!

40. TREATMENT INCLUDES INHIBITORS OF ENZYMES:1. Reverse transcriptase inhibitor This enzyme allows viral RNA to code for DNA2. Protease inhibitor This enzyme allows viral proteins to be cut and fit into the final virus3. Integrase inhibitor This enzyme allows the virus DNA to join the cell’s DNA in the nucleus

41. Drug-resistant HIV

42. Cancer Causing Viruses • About 20% of cancers seem to be caused by viruses. • First identified in Chickens…Rous Sarcoma Virus…. • “One great strategy for the viruses to spread like mad was to convince the cells harboring viral DNA to spread like mad too. The viruses did this by disrupting the genetic governors* that prevent cells from dividing rapidly. A runaway tumor was the result.”The Violinist’s Thumb, Sean Kean • *Those ‘governors’ are the genes that control cell division.

43. Tumor Viruses • Tumor: uncontrolled growth of a single cell producing a mass of undifferentiated cells. • Can be due to viral infection: • Viral genome inserts into eukaryotic host genome • Forces host to replicate viral and host DNA more than normal disrupts host cell’s ability to control cell cycle. tumor

44. DNA viruses that cause cancer: • Human Papilloma Virus (HPV) causes transformation in cells through interfering with tumor suppressor proteins such as p53.. Interfering with the action of p53 allows a cell infected with the virus to move into a different stage of the cell cycle, enabling the virus genome to be replicated. Forcing the cell into the S phase of the cell cycle could cause the cell to become transformed. Some types of HPV increase the risk of cervical cancer. • Kaposi’s Sarcoma Herpes Virus is associated with Kaposi’s Sarcome, a type of skin cancer often seen in AIDS patients. • Epstein Barr Virusis associated with four types of cancers • RNA viruses • Hepatitis C Virus as well • Human T-Lymphotrophic Virus (HTLV-1).

45. Tree man…. Infected with HPV • his affliction is caused by the Human Papilloma Virus (HPV), a fairly common infection that usually causes small warts to develop on sufferers. • Dede's problem is that he has a rare genetic fault that impedes his immune system, meaning his body is unable to contain the warts. • The virus was therefore able to "hijack the cellular machinery of his skin cells", ordering them to produce massive amounts of the substance that caused the tree-like growths known as "cutaneous horns" on his hands and feet. http://www.telegraph.co.uk/news/worldnews/1569156

46. polio Viruses infect many organisms, including bacteria, plants, and animals; cause much agricultural loss, mild to deadly human diseases (cold, flu, chickenpox, herpes, rabies, AIDS, some types of cancer). ebola flu smallpox

47. Aren’t you glad we don’t get smallpox anymore? Smallpox has been eliminated from the world as a result of immunizations

48. Vertebrates defend against viruses through: antibody-based immunity or cellular immunity. 1. Immune system produces specific proteins (antibodies) that recognize and bind viral particles, thereby blocking their replication. • Immune cells called T cells recognize and destroy cells harboring viruses (cellular immunity). • After first infection, body retains clones of antibody or T cells directed against that viral strain: Rapid defense is mounted upon second infection. This is what happened when you recovered from chicken pox.

49. This immune memory is the basis of vaccination; A vaccine consists of killed or nonfunctional infectious agents or parts of those germs that trigger an immune response in body without causing disease symptoms. Upon subsequent infection with active virus or bacteria the body can then launch a rapid attack against the pathogen and prevent disease. Dr. Edward Jenner produced the first vaccine that was used widely. He injected cowpox pus into a boy (His son!); the boy got cowpox and recovered. Jenner then injected the boy with smallpox pus and waited…..the boy did not get smallpox.

50. Vaccines early warning for immune system