Viruses

1. Viruses AP Biology – From Ch. 18

2. Structure of Viruses • Genome enclosed in a protective coat • Genome may be DNA or RNA • Protective coat is protein - CAPSID

3. Structure of Viruses • Some animal viruses also have a membrane called a viral envelope that surrounds the capsid • These membranes are derived from the host cell, but also contain molecules of viral origin.

4. Viral Reproduction - Intro • Viruses can reproduce only within a host cell. • Obligate intracellular parasites • Lack enzymes for metabolism • Have no ribosomes for making proteins • Packaged sets of genes • ARE VIRUSES ALIVE?

5. Viruses and Hosts • Each different viral type can infect only a limited range of host cells • May infect only a single species – ONLY E.coli • May infect a range of species • Rabies infects mammals • Also, viruses of eukaryotes tend to be tissue specific • Cold viruses - upper resp.; rabies – nervous tissue

6. Different Viruses

7. Viral Reproduction – Cell Entry • Viral genome must gain entry into a cell • Viruses identify their host cells by a “lock and key” fit between proteins on the outside of the virus and receptors on the cell surface of the host.

8. Types of Viral Cycles • There are two main types of viral cycles • Lytic cycle • Lysogenic cycle

9. Generalized Viral Infection • Viral capsid (or envelope) docks to receptors on surface of cell to be infected. • The viral genome (DNA or RNA) is injected into cell.

10. Generalized Viral Infection • Once inside host, viral genome reprograms the cell to • Copy the viral nucleic acid • Manufacture viral proteins (components of the capsid, for example)

11. Generalized Viral Infection • If the genetic material is DNA • The host cell’s own DNA polymerases replicate the viral DNA. • If the genetic material is RNA • The virus will have to do a tricky little extra step to make DNA from its own RNA genome. More later on this.

13. Generalized Viral Infection • Virus diverts host’s resources from host needs to viral reproduction. • Nucleotides • Enzymes • Ribosomes • tRNAs • Amino acids • ATP • And more…

14. Generalized Viral Infection • Once components are made (viral genomes and capsid components) they self assemble into new viral particles.

16. Generalized Viral Infection • Often, the cycle is completed when hundreds to thousands of viruses emerge from the host cell • Cell is often destroyed in the process • Some symptoms of human viral infections result from cellular damage and death; also from effects of body’s response to this destruction. • Those viruses that exit a cell are now able to infect other cells.

17. Viral Cycles – The Lytic Cycle • The lytic cycle culminates in death of the host cell. • Lytic = Lyses = Cell ruptures • This happens when new viral particles are released from host. • Virulent Virus – a virus that reproduces by the lytic cycle

19. Limitations on the Lytic Cycle • Examples of defenses against viruses can be found in studying bacteria and phages: • Natural selection favors mutants with receptor sites that aren’t recognized by a phage. • If a phage enters a bacterium, restriction nucleases (enzymes) may break it dow

20. Limitations on the Lytic Cycle • Restriction nucleases (enzymes) • Enzymes that recognize and destroy foreign DNA in a bacterium. • The bacterial cell’s own DNA is modified in a way that prevents attack by its restriction enzymes.

21. Limitations on the Lytic Cycle • Of course, natural selection also favors viral mutants that evolve resistance to these enzymes • Parasite-host relationships are in constant evolutionary flux • One continually tries to “outwit” the other.

22. Limitations on the Lytic Cycle • Finally, many phages (and other viruses, too) can check their own activity • Instead of lysing their host cells, they coexist with them • This is called the lysogenic cycle.

23. The Lysogenic Cycle • Replicates viral genome without destroying the host • Temperate viruses – viruses that are able to use both lysogenic and lytic cycles

24. Lysogenic Cycle • Example – Lambda bacteriophage • Lambda can enter an E. coli cell and immediately enter a lytic cycle OR it can enter a lysogenic cycle

25. Lysogenic Cycle - Lambda • Lambda DNA molecule is incoporated into the host cell’s chromosome • It is then known as a PROPHAGE. • One prophage gene codes for a protein that represses most of the other prophage genes. • Thus the prophage genome is mostly silent within the bacterium.

26. Lysogenic Cycle - Lambda • If the virus (prophage) is dormant, then how does it reproduce? • Each time the E.coli cell prepares to divide, it replicates the phage DNA as it is replicating its own DNA. • Copies are then passed to daughter cells. • A single infected cell can give rise to a whole population of infected cells. • The virus propagates without killing the host.

28. Lysogenic Cycle – Lambda • Phages in the lysogenic state CAN give rise to active phages that will lyse the host cell. • The lambda genome must exit the host genome. • Then lytic cycle proceeds • Usually it is an environmental trigger that switches the phage from lysogenic to lytic • Radiation or chemical

29. Animal Viruses • Animal viruses follow the basic schemes of lytic and lysogenic cycles but with many variations. • Key variables in animal viruses include: • Type of nucleic acid of viral genome • Presence or absence of a membranous envelope

30. Viral Envelopes in Animal Viruses • Viral envelope – outer membrane outside the capsid. • Generally a lipid bilayer • Glycoproteins protrude from cell surface.

31. Viral Envelopes in Animal Viruses • Helps the parasite enter the host cell. • Glycoproteins bind to specific receptor molecules on cell surface. • Viral envelope fuses with host’s membrane. • Transports genome and capsid into cell.

32. Viral Envelopes in Animal Viruses • After entering the cell… • Cellular enzymes remove the capsid • Viral genome replicates and directs synthesis of new viral proteins including glycoproteins for new envelopes. • ER of host makes these • They are transported to cell surface. • They are clustered in patches that serve as exit points for the “offspring” virus particles. • New viruses bud from these points – a lot like exocytosis • Bottom line: Viral envelope is derived from host’s own membrane. • Does not necessarily kill the host cell – unlike lytic cycle.

34. Viral Envelopes in Animal Viruses • Some animal viruses have envelopes made from NUCLEAR membranes • Herpesvirus • Genome is DNA • Viruses reproduce w/in the nucleus using cell enzymes to replicate and transcribe DNA • CAN become integrated into host’s DNA

35. Provirus • Provirus – genome of an animal virus that becomes integrated into the host cell’s genome. • Similar to bacterial prophage. • Herpesviruses – Once acquired, herpes infections (cold sores and others) tend to recur throughout life. • Between episodes, provirus remains latent. • Stress may cause provirus to leave host’s genome and become active – results in blisters, active infections.

36. RNA as Viral Genetic Material • Large variety of RNA genomes among animal viruses • Classified according to: • Strandedness of the RNA molecule • Can be single or double stranded • How the RNA functions in the host cell

37. RNA as Viral Genetic Material • Class IV • Class V • Class VI

38. RNA as Viral Genetic Material • Class IV • Can directly serve as mRNA • Can be translated into viral proteins immediately

39. RNA as Viral Genetic Material • Class V • RNA genome serves as a template for mRNA synthesis • RNA genome is transcribed into complementary RNA which serves as mRNA to make viral proteins • This transcribed mRNA also serves as a template to make more viral genome RNA • Virus uses an enzyme packaged with the genome inside the capsid to do all this.

40. RNA as Viral Genetic Material • Class VI • Most complex cycle • Newly made DNA integrates into host as a provirus • RETROVIRUSES – “backward” • Genetic info. Flows in a “reverse direction” • RNA > DNA • Retroviruses are packaged with a special enzyme – Reverse transcriptase • Transcribes DNA from virus’ RNA genome • Host’s RNA polymerase then transcribes viral DNA into RNA molecules that can become • mRNA to make viral proteins OR • RNA viral genomes to be packaged into new virus particles

41. HIV – A particularly important retrovirus • HIV is a retrovirus • Causes AIDS

43. Affects of Viruses in Animals • Amount of damage a virus causes often depends on the type of tissue it infects • Cold viruses infect epithelium of respiratory tract which efficiently repairs itself. • Poliovirus attacks nerve cells which cannot divide and cannot be replaced. • Symptoms like fever, aches and inflammation are usually due to the body’s own defenses fighting the virus.

44. Vaccines • Vaccine • harmless variants of pathenogenic microbes • Stimulate the immune system to mount defenses against the actual pathogen

45. First Vaccine • Against smallpox • Consisted of cowpox virus • Edward Jenner • Milkmaids who contracted cowpox were resistant to smallpox • Scratched a boy with a needle bearing fluid from a sore of a milkmaid with cowpox. • Boy was later exposed to smallpox and resisted the disease.

46. Why Did the Vaccine Work? • Cowpox and smallpox are so similar that the immune system cannot distinguish them. • Vaccination with cowpox virus sensitizes the immune system to cow/smallpox and if ever exposed to smallpox (or cowpox again), the defenses will be so strong that the virus will be overwhelmed before it can cause illness. • Jenner’s vaccine DID have to cause illness in order to confer immunity. Modern vaccines usually do not. • Fundamental of Immune System: Once you have been made ill by a virus (or other microbe) you cannot be made ill by that same virus again. Immune system is sensitized and will recognize it. • You never catch the same cold twice.

47. Why Did the Vaccine Work? • Jenner’s vaccine DID have to cause illness in order to confer immunity. Modern vaccines usually do not. • Fundamental of Immune System: Once you have been made ill by a virus (or other microbe) you cannot be made ill by that same virus again. Immune system is sensitized and will recognize it. • You never catch the same cold twice.

48. Cures for Viral Infections? • Prevention – Yes – Vaccines • Cures – No • Antibiotics work only on bacteria • Some drugs have been discovered that interfere with viral nucleic acid synthesis • AZT – inhibits HIV by interfering with reverse transcriptase

49. Emerging Viruses • Viruses sometimes appear to come out of nowhere • HIV • Hantavirus • Ebola • New strains of influenza each year

50. 3 Processes in Emergence • Mutation of existing viruses • RNA viruses have a high rate of mutation • No proofreading found in DNA replication • May mutate enough to “outwit” immune systems of people immune to previous versions.