Chapter 19

1. Chapter 19 Viruses

2. Microbial Model Systems • Are viruses living organisms? • Maybe • The origins of molecular biology lie in early studies of viruses that infect bacteria T4 bacteriophage attacking E. coli

3. Virus • Bacteria are prokaryotes with cells much smaller and more simply organized than those of eukaryotes • Viruses are smaller and simpler than bacteria Bacterium Animal cell Animal cell nucleus 0.25 µm

4. Viruses • Viruses were detected indirectly long before they were actually seen • Tobacco mosaic disease stunts growth of tobacco plants and gives their leaves a mosaic coloration • In the late 1800s, researchers hypothesized that a particle smaller than bacteria caused the disease • In 1935, this hypothesis was confirmed by crystallizing the infectious particle, tobacco mosaic virus (TMV)

5. Structure of Viruses • Viruses are not cells • Viruses are very small infectious particles consisting of nucleic acid enclosed in a protein coat and, in some cases, a membranous envelope • Viral genomes may consist of: • Double- or single-stranded DNA • Double- or single-stranded RNA Depending on its type of nucleic acid, a virus is called a DNA virus or an RNA virus

6. Membranousenvelope Capsomere RNA RNA DNA Capsid DNA Head Tailsheath Capsomereof capsid Tailfiber Glycoproteins Glycoprotein 80–200 nm (diameter) 70–90 nm (diameter) 80  225 nm 18  250 nm 50 nm 50 nm 50 nm 20 nm (a) (b) Adenoviruses Tobaccomosaic virus (c) Influenza viruses (d) Bacteriophage T4

7. RNA DNA Capsomere capsid- is the protein shell that encloses the viral genome; each protein subunit is a capsomere Capsomere of capsid Glycoprotein 18 x 250 nm 70–90 nm (diameter) 50 nm 20 nm (a) Tobacco mosaic virus (b) Adenoviruses

8. Membranous envelope RNA Capsid • Some viruses have membranous envelopes that help them infect hosts • surround the capsids of influenza viruses and many other viruses found in animals • are derived from the host cell’s membrane, contain a combination of viral and host cell molecules Glycoproteins 80–200 nm (diameter) 50 nm (c) Influenza viruses

9. Head DNA Tail sheath • Bacteriophages, also called phages, are viruses that infect bacteria • They have: • the most complex capsids found among viruses • an elongated capsid head that encloses their DNA • a protein tailpiece that attaches the phage to the host and injects the phage DNA inside Tail fiber 80 x 225 nm 50 nm (d) Bacteriophage T4

10. VIRUS Viral Replicative Cycle Entry into cell and uncoating of DNA DNA Capsid Transcription Replication • Viruses are obligate intracellular parasites, which means they can reproduce only within a host cell • Each virus has a host range, a limited number of host cells that it can infect • Once a viral genome has entered a cell, the cell begins to manufacture viral proteins • The virus makes use of host enzymes, ribosomes, tRNAs, amino acids, ATP, and other molecules HOST CELL host enzymes replicate the viral genome Viral DNA mRNA Viral DNA Capsid proteins Self-assembly of new virus particles and their exit from cell

11. Reproductive Cycles of Phages • Phages are the best understood of all viruses • Bacteria have defenses against phages, including restriction enzymes that recognize and cut up certain phage DNA • Phages have two reproductive mechanisms: 1. the lytic cycle 2. the lysogenic cycle

12. Attachment 1 Attachment Attachment Attachment Attachment 1 1 1 1 The Lytic Cycle 2 2 2 2 Entry of phage DNA and degradation of host DNA Entry of phage DNA and degradation of host DNA Entry of phage DNA and degradation of host DNA Entry of phage DNA and degradation of host DNA culminates in the death of the host cell 5 Release digests the host’s cell wall Phage assembly Phage assembly produces new phages 4 4 Assembly Assembly 3 3 3 Synthesis of viral genomes and proteins Synthesis of viral genomes and proteins Synthesis of viral genomes and proteins • A phage that reproduces only by the lytic cycle is called a virulent phage Head Tail Tail fibers Head Tail Tail fibers

13. The Lysogenic Cycle • The lysogenic cycle replicates the phage genome without destroying the host • The viral DNA molecule is incorporated by genetic recombination into the host cell’s chromosome; this integrated viral DNA is known as a prophage Daughter cell with prophage Phage DNA The phage attaches to a host cell and injects its DNA. Many cell divisions produce a large population of bacteria infected with the prophage. Phage DNA circularizes Phage Bacterial chromosome Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Lytic cycle Lysogenic cycle The bacterium reproduces normally, copying the prophage and transmitting it to daughter cells. Certain factors determine whether The cell lyses, releasing phages. Lytic cycle is induced Lysogenic cycle is entered or Prophage temperate phage New phage DNA and proteins are synthesized and assembled into phages. Phage DNA integrates into the bacterial chromosomes, becoming a prophage.

14. • Lysis of host cell causes release of progeny phages • Genome integrates into bacterialchromosome as prophage, which(1) is replicated and passed on todaughter cells and(2) can be induced to leave the chromo-some and initiate a lytic cycle The phage attaches to ahost cell and injects its DNA. PhageDNA Bacterialchromosome Prophage Lysogenic cycle Lytic cycle • Virulent or temperate phage • Temperate phage only • Destruction of host DNA • Production of new phages

15. Two key variables in classifying viruses that infect animals: • DNA or RNA • single-stranded (ss) double-stranded (ds) http://en.wikipedia.org/wiki/Baltimore_classification

16. DNA HPV RNA

17. Retroviruses • The broadest variety of RNA genomes is found in viruses that infect animals • Retroviruses- use reverse transcriptase to copy their RNA genome into DNA • Human immunodeficiency virus (HIV) is the retrovirus that causes acquired immunodeficiency syndrome (AIDS) Class VI. ssRNA; template for DNA synthesis

18. The viral DNA that is integrated into the host genome is called a provirus Unlike a prophage, a provirus remains a permanent resident of the host cell The host’s RNA polymerase transcribes the proviral DNA into RNA molecules The RNA molecules function both as mRNA for synthesis of viral proteins and as genomes for new virus particles released from the cell Membrane of white blood cell HIV HOST CELL reverse transcriptase- catalyzes the synthesis of a DNA strand complementary to the viral RNA and a second DNA strand complementary to the 1st Viral RNA RNA-DNA hybrid 0.25 µm HIV entering a cell DNA NUCLEUS Provirus Chromosomal DNA RNA genome for the next viral generation mRNA New HIV leaving a cell

19. Viral Disease • Diseases caused by viral infections affect humans, agricultural crops, & livestock worldwide • Viruses may damage or kill cells by causing the release of hydrolytic enzymes from lysosomes • Some viruses cause infected cells to produce toxins that lead to disease symptoms • Smaller, less complex entities called viroids and prions also cause disease in plants and animals

20. vaccines- are harmless derivatives of pathogenic microbes that stimulate the immune system to mount defenses against the actual pathogen can prevent certain viral illnesses Hepatitis B, A Polio (IPV) Rotavirus MMRV- Measles, Mumps, Rubella, Varicella (chicken pox) HPV Other crucial childhood vaccines that protect against bacteria: DTaP (Diptheria, Tetanus, Pertussis [whooping cough]) Hib (Haemophilus influenzae type b) Pneumococcal Vaccines

21. Viral infections cannot be treated by antibiotics antiviral drugs- can help to treat, though not cure, viral infections by interfering with viral replication • HIV can be treated • with the drug AZT. AZT has a 100- to 300-fold greater affinity for the HIV reverse transcriptase, as compared to the human DNA polymerase http://en.wikipedia.org/wiki/Zidovudine