1. Fig. 19-1 0.5 µm Chapter 19 1.The simplest form of life 2.Exist on the borderline between the living and the inanimate, non-biological world 3. Reveal more complex life 4. Human disease

2. Fig. 19-9 (a) The 1918 flu pandemic (b) Influenza A H5N1 virus (c) Vaccinating ducks 0.5 µm

3. 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 In 1935, Wendell Stanley confirmed this hypothesis by crystallizing the infectious particle, now known as tobacco mosaic virus (TMV)

4. Some evolutionary biologist: make more copies of their genome Viruses : nucleic acid + a protein coat (capsid), protection and entrance 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 NA+ protein coat= nucleocapsid, in animal virus +a membranous envelope (the lipid membrane) A good source of pure DNA before the advent of gene cloning –eg: SV40 virus (a ds DNA virus, 5 genes Obligate parasite (either as degenerate cells or renegade cellular genes) Rapid genetic change has obscured or erased ant relationships Structure of Viruses

5. 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 Virus particle or virion

6. viral envelopes Some viruses have membranous envelopes that help them infect hosts –(membrane-scavenging strategy) These viral envelopes surround the capsids of influenza viruses and many other viruses found in animals –(encephalitis virus, smallpox, rabies, herpes virus and the HIV) Viral envelopes, which are derived from the host cell ’ s membrane, contain a combination of viral (virus-encoded proteins) and host cell molecules –(N-terminal protrude outwrd, C-terminal ofter contact the nucleocapsid) –Easily dissolved by detergents but gastrointestinal viruses (including poliovirus) have purely protein

7. Bacteriophages 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

8. 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

9. 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

10. Temperate phages 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

11. 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.Adsorption  penetration  2.  cytoplasm (smallpox and RNA virus) or 3.  nucleus (DNA virus)

12. 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

13. 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.

14. 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?

15. The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. Viral genomes may be single- stranded (ss) or double-stranded (ds), RNA or DNA, and may or may not use reverse transcriptase (RT). Additionally, ssRNA viruses may be either sense (+) or antisense (−). This classification places viruses into seven groups:mRNAreverse transcriptasesense

16. Table 19-1

17. Table 19-1a 1.Host cell DNA polymerase and RNA polymerase to transcribe 2.The enzymes of DNA replication are generally not expressed in quiescent ceel (G0)  most of the cell infected will be in G0 3. : have large genomes that contain greater than 60 genes, encode rheir own DNA polymerase and ensure their ability replicate in quiescent cells. 4.Other viruses circumvent this problem by producing a protein that induces the resting host cell to enter the active cell cycle 5.5. the virus and the viral growth- promoting proteins can drive the host cell into unceasing growth and cell division (oncogene) 6.HPV: cervical carcinoma EB: mononucleosis Burkitt’s lymphoma (a childhood tumor) in central Africa Nasopharyngeal carcinoma in Southeast Asia google

18. Table 19-1b 德國麻疹 馬象皮病毒 SS DNA 1.A simple genome 2.Have a simple genome—one gene for a viral nucleocapside protein and another gene for a DNA replication enzyme 3.only template for transcription  ds DNA, 3’ as a primer (+) ssRNA+ an mRNA 1.pico—small 2.mRNA  make viral proteins  that can replicate the ssRNA genome as well as the proteins needed for the capsid. Fig 19-7 + -

19. 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 The reproductive cycle of an enveloped RNA virus (Class V) --- Template for mRNA synthesis

20. 2009 flu pandemic

21. Influenza hemagglutinin (HA) or haemagglutinin (British English)British English 1.is a type of hemagglutinin found on the surface of the influenza viruses.hemagglutinin influenzaviruses 2.2. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected.antigenic glycoproteincell 3. The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitroproteinerythrocytesagglutinate

22. Viral neuraminidase is an enzyme on the surface of influenza virusesenzymeinfluenza viruses that enables the virus to be released from the host cell. Drugs that inhibit neuraminidase, known as neuraminidase inhibitors, are used to treat influenza.neuraminidase inhibitors When influenza virus reproduces, it attaches to the cell surface using hemagglutininhemagglutinin, a molecule found on the surface of the virus which binds to sialic acid groups. sialic acid Sialic acids are found on various glycoproteins at the host cell surface,glycoproteins and the virus exploits these groups to bind the host cell. In order for the virus to be released from the cell, neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins. In some viruses, a hemagglutinin-neuraminidase protein combines the neuraminidase and hemagglutinin functions in a single protein.hemagglutinin-neuraminidasehemagglutinin

23. Influenza virus replication

25. De Clercq Nature Reviews Drug Discovery 5, 1015–1025 (December 2006) | doi:10.1038/nrd2175

26. 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 HIV (human immunodeficiency virus) is the retrovirus that causes AIDS (acquired immunodeficiency syndrome)

27. Fig. 19-8 Glycoprotein Viral envelope Capsid RNA (two identical strands) Reverse transcriptase HIV Membrane of white blood cell HIV entering a cell 0.25 µm Viral RNA RNA-DNA hybrid HOST CELL Reverse transcriptase DNA NUCLEUS Provirus Chromosomal DNA RNA genome for the next viral generation mRNA New virus New HIV leaving a cell

28. 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

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

30. Emerging Viruses Emerging viruses are those that appear suddenly or suddenly come to the attention of scientists Severe acute respiratory syndrome (SARS) recently appeared in China Outbreaks of “ new ” viral diseases in humans are usually caused by existing viruses that expand their host territory

31. Structure of the Virus

32. Evolution of viruses Hypothesis: naked bits of cellular nucleic acisds that moved from one cell to another Mobile genetic elements –Plasmid –transposons

33. 1.A specific cellular tRNA acts as a primer and hybridizes to a complementary part of the virus genome called the primer binding site or PBS 2.Complementary DNA then binds to the U5 (non-coding region) and R region (a direct repeat found at both ends of the RNA molecule) of the viral RNA 3.A domain on the reverse transcriptase enzyme called RNAse H degrades the 5’ end of the RNA which removes the U5 and R region 4.The primer then ‘jumps’ to the 3’ end of the viral genome and the newly synthesised DNA strands hybridizes to the complementary R region on the RNA 5.The first strand of complementary DNA (cDNA) is extended and the majority of viral RNA is degraded by RNAse H 6.Once the strand is completed, second strand synthesis is initiated from the viral RNA 7.There is then another ‘jump’ where the PBS from the second strand hybridizes with the complementary PBS on the first strand 8.Both strands are extended further and can be incorporated into the hosts genome by the enzyme integrase

34. 2. RNA-dependent RNAP 1.RNase H 3. DNA-dependent DNAP Reverse transcriptase Specific tRNA as primer

35. Fig. 19-10 Viral infection of plants

36. Fig. 19-11 Prion Normal protein Original prion New prion Aggregates of prions Model for how prions propagate

37. Fig. 19-UN3