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Chapter 19 Viruses 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 • Bacteria are prokaryotes with cells much smaller and more simply organized than those of eukaryotes • Viruses are smaller and simpler than bacteria Virus Bacterium Animal cell Animal cell nucleus 0.25 µm 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) 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: 1. Double- or single-stranded DNA 2. Double- or single-stranded RNA Depending on its type of nucleic acid, a virus is called a DNA virus or an RNA virus Capsomere RNA DNA Membranous RNA envelope Capsid Head DNA Tail sheath Capsomere of capsid Tail fiber Glycoprotein 18 250 nm 20 nm (a) Tobacco mosaic virus Glycoproteins 70–90 nm (diameter) 80–200 nm (diameter) 50 nm (b) Adenoviruses 80 225 nm 50 nm 50 nm (c) Influenza viruses (d) Bacteriophage T4 RNA DNA Capsomere capsidis the protein shell that encloses the viral genome; Capsomere each protein subunit is a of capsid capsomere 18 x 250 nm 20 nm (a) Tobacco mosaic virus Glycoprotein 70–90 nm (diameter) 50 nm (b) Adenoviruses • Some viruses have membranous envelopes that help them infect hosts – surround the capsids of influenza viruses and many other viruses found in animals Membranous envelope RNA Capsid Glycoproteins 80–200 nm (diameter) – are derived from the host cell’s membrane, contain a combination of viral and host cell molecules 50 nm (c) Influenza viruses • • 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 Head DNA Tail sheath Tail fiber 80 x 225 nm – a protein tailpiece that attaches the phage to the host and injects the phage DNA inside 50 nm (d) Bacteriophage T4 Viral Replicative Cycle • • 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 Entry into cell and uncoating of DNA VIRUS DNA Capsid Transcription Replication HOST CELL host enzymes replicate the Viral DNA viral genome mRNA Viral DNA Capsid proteins Self-assembly of new virus particles and their exit from cell 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 1 Attachment The Lytic Cycle culminates in the death of the host cell 5 Release 2 Entry of phage DNA and degradation of host DNA digests the host’s cell wall Phage assembly produces new phages 4 Assembly 3 Synthesis of viral genomes and proteins Head Tail Tail fibers • A phage that reproduces only by the lytic cycle is called a virulent phage 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 Phage DNA Daughter cell with prophage 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 Lytic cycle The cell lyses, releasing phages. Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Lysogenic cycle Certain factors determine whether Lytic cycle or Lysogenic cycle is induced is entered New phage DNA and proteins are synthesized and assembled into phages. The bacterium reproduces normally, copying the prophage and transmitting it to daughter cells. Prophage Phage DNA integrates into the bacterial chromosomes, becoming a prophage. temperate phage Phage DNA The phage attaches to a host cell and injects its DNA. Bacterial chromosome Prophage Lysogenic cycle Lytic cycle • Virulent or temperate phage • Temperate phage only • Destruction of host DNA • Genome integrates into bacterial • Production of new phages chromosome as prophage, which • Lysis of host cell causes release (1) is replicated and passed on to of progeny phages daughter cells and (2) can be induced to leave the chromosome and initiate a lytic cycle 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 DNA HPV RNA Retroviruses • The broadest variety of RNA genomes is found in viruses that infect animals • Retrovirusesuse 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 The viral DNA that is integrated into the host genome is called a provirus HIV Membrane of white blood cell HOST CELL Unlike a prophage, a provirus remains a permanent resident of the host cell reverse transcriptasecatalyzes the synthesis of a DNA strand complementary to the viral RNA and a second DNA strand complementary to the 1st Viral RNA 0.25 µm HIV entering a cell RNA-DNA hybrid DNA NUCLEUS Provirus The host’s RNA polymerase transcribes the proviral DNA into RNA molecules Chromosomal DNA RNA genome for the next viral generation The RNA molecules function both as mRNA for synthesis of viral proteins and as genomes for new virus particles released from the cell New HIV leaving a cell mRNA 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 Vaccines • vaccinesare 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 Viral infections cannot be treated by antibiotics antiviral drugscan 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