CAMPBELL BIOLOGY IN FOCUS URRY • CAIN • WASSERMAN • MINORSKY • REECE 17 Viruses Lecture Presentations by Kathleen Fitzpatrick and Nicole Tunbridge, Simon Fraser University © 2016 Pearson Education, Inc. SECOND EDITION Structure of Viruses Even the largest known virus is barely visible under the light microscope Viruses are not composed of cells A virus is an infectious particle consisting of little more than genes packaged into a protein coat and, in some cases, a membranous envelope Viruses lead “a kind of borrowed life,” existing in a shady area between life-forms and chemicals Chapter 17 Viruses Key Concepts 17.1 A virus consists of a nucleic acid surrounded by a protein coat 17.2 Viruses replicate only in host cells 17.3 Viruses and prions are formidable pathogens in animals and plants © 2016 Pearson Education, Inc. Are the tiny viruses leaving this E. coli cell alive? 0.5 mm Are Viruses “alive” Viruses cannot replicate or carry out metabolic activities outside of a host cell. Most virologists would probably agree that viruses are not alive but lead “a kind of borrowed life.” Components of virus: 1. Genome 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 Components of virus: 2. Capsid A capsid is the protein shell that encloses the viral genome Capsids are built from protein subunits called capsomeres The number of different kinds of proteins making up the capsid is usually small. A capsid can have various structures Components of virus: 3. Envelope Some viruses have membranous envelopes An animal virus with an envelope uses it to enter the host cell The envelope is derived from the plasma membrane of a host cell, although some of the molecules on the envelope are specified by the genome of the virus Viral structure RNA Capsomere DNA Membranous envelope RNA Capsid Head DNA Tail sheath Capsomere of capsid Tail fiber 18 250 nm 80 nm (a)Tobacco mosaic virus © 2016 Pearson Education, Inc. Glycoprotein Glycoproteins 70–90 nm (diameter) 80–200 nm (diameter) 50 nm (b) Adenoviruses 50 nm (c) Influenza viruses 80 225 nm 50 nm (d) Bacteriophage T4 Viruses replicate only in host cells Viruses are obligate intracellular parasites, which means they can replicate only within a host cell Each virus has a host range, a limited number of host cells that it can infect Bacteriophages, also called phages, are viruses that infect bacteria 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 © 2016 Pearson Education, Inc. General Features of Viral Replicative Cycles 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 Viral nucleic acid molecules and capsomeres spontaneously selfassemble into new viruses These exit from the host cell, usually damaging or destroying it © 2016 Pearson Education, Inc. Animation: Simplified Viral Replicative Cycle © 2016 Pearson Education, Inc. Figure 17.3 VIRUS DNA Entry and uncoating Replication Transcription and manufacture of capsid proteins Capsid HOST CELL Viral DNA mRNA Viral DNA © 2016 Pearson Education, Inc. Capsid proteins Self-assembly of new virus particles and their exit from the cell Replicative Cycles of Phages Phages are the best understood of all viruses Phages have two reproductive mechanisms: the lytic cycle and the lysogenic cycle © 2016 Pearson Education, Inc. The Lytic Cycle The lytic cycle is a phage replicative cycle that culminates in the death of the host cell New viruses are produced using host cell components The host cell lyses (breaks open) , and viruses are released A phage that reproduces only by the lytic cycle is called a virulent phage © 2016 Pearson Education, Inc. Animation: Phage T4 Lytic Cycle © 2016 Pearson Education, Inc. The lytic cycle Attachment Release Entry of phage DNA and degradation of host DNA Phage assembly Self-assembly Head Tail Tail fibers © 2016 Pearson Education, Inc. Synthesis of viral genomes and proteins The Lysogenic Cycle The lysogenic cycle replicates the phage genome without destroying the host Viral DNA is inserted into the host chromosome Viral DNA is duplicated along with the host chromosome during each cell division The inserted phage DNA is called a prophage Most prophage genes are inactive Environmental signals can cause a switch to the lytic cycle © 2016 Pearson Education, Inc. Animation: Phage Lysogenic and Lytic Cycles © 2016 Pearson Education, Inc. The lytic and lysogenic cycles of phage λ, a temperate phage The phage attaches to a host cell and injects its DNA. Phage DNA Prophage Bacterial chromosome Lytic cycle • Virulent or temperate phage • Destruction of host DNA • Production of new phages • Lysis of host cell causes release of progeny phages © 2016 Pearson Education, Inc. 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 Bacterial Defenses Against Phages Natural selection favors mutant bacteria with surface proteins that are not recognized by a particular phage Phage DNA is often identified as foreign and cut up by restriction enzymes The bacterium’s own DNA is methylated in a way that prevents attack by its own restriction enzymes © 2016 Pearson Education, Inc. The CRISPR-Cas system is also used by bacteria and its offspring to protect against future infection by the same type of phage © 2016 Pearson Education, Inc. RNA as Viral Genetic Material Retroviruses use reverse transcriptase to copy their RNA genome into DNA HIV (human immunodeficiency virus) is the retrovirus that causes AIDS (acquired immunodeficiency syndrome) © 2016 Pearson Education, Inc. Viral DNA that is integrated into the host genome is called a provirus A provirus is 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 viruses released from the cell © 2016 Pearson Education, Inc. Animation: HIV Replicative Cycle © 2016 Pearson Education, Inc. The replicative cycle of HIV, the retrovirus that causes AIDS Glycoprotein Viral envelope Membrane of HIV white blood cell Capsid RNA (two identical strands) HOST CELL Reverse HIV transcriptase Reverse transcriptase Viral RNA RNA-DNA hybrid 0.25 𝛍m HIV entering a cell DNA NUCLEUS Chromosomal DNA RNA genome for the progeny viruses Provirus mRNA New virus New HIV leaving a cell © 2016 Pearson Education, Inc. Viral Diseases in Animals 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 Others have molecular components such as envelope proteins that are toxic © 2016 Pearson Education, Inc. Vaccines are the major medical tool for preventing viral infections A vaccine is a harmless derivative of a pathogen that stimulates the immune system to mount defenses against the harmful pathogen Antibiotics are powerless against viruses Antiviral drugs can help to treat, though not cure, viral infections © 2016 Pearson Education, Inc. Receptor proteins on the surfaces of cells are important in treatment or prevention of viral infection Some people have been found to be resistant to HIV infection These people have an unusual form of the CCR5 protein, one of the proteins to which HIV must bind in order to infect most cells A drug that masks the CCR5 protein is being tested currently © 2016 Pearson Education, Inc. Figure 17.9 HIV Receptor (CD4) Co-receptor (CCR5) (a) © 2016 Pearson Education, Inc. Receptor (CD4) Plasma but no CCR5 membrane (b) Influenza Influenza viruses infect the epithelial lining of the upper respiratory system Cause the “flu”, a highly contagious respiratory illness Influenza viruses are RNA viruses and have a high rate of mutation Source: www.cdc.gov/flu/about/viruses/change.htm influenza Seasonal flu vaccines are directed against surface proteins (H & N) of the common circulating influenza strains Primes the immune system so it can quickly mount an attack if the influenza virus is encountered (involves “memory” T-lymphocytes and antibodies). Genetic Drift Emerging Viruses Genetic Shift Image credit: jbiol.com/content/figures/jbiol147-1-l.jpg Emerging Viruses Viruses that suddenly become apparent are called emerging viruses HIV is a classic example The Ebola virus, recognized initially in 1976 in central Africa, causes hemorrhagic fever, an often fatal syndrome © 2016 Pearson Education, Inc. Ebola viruses infecting a monkey cell © 2016 Pearson Education, Inc. In 2009 a general outbreak, or epidemic, of a flu-like illness occurred in Mexico and the United States; the virus responsible was named H1N1 H1N1 spread rapidly, causing a pandemic, or global epidemic © 2016 Pearson Education, Inc. Influenza in humans 1 𝛍m (a) 2009 pandemic H1N1 influenza A virus © 2016 Pearson Education, Inc. (b) 2009 pandemic screening Three processes contribute to the emergence of viral diseases The mutation of existing viruses, which is especially high in RNA viruses Dissemination of a viral disease from a small, isolated human population, allowing the disease to go unnoticed before it begins to spread Spread of existing viruses from animal populations; about three-quarters of new human diseases originate this way © 2016 Pearson Education, Inc. Evolution of Viruses Viruses do not fit our definition of living organisms Since viruses can replicate only within cells, they probably evolved after the first cells appeared Candidates for the source of viral genomes are plasmids (circular DNA in bacteria and yeasts) and transposons (small mobile DNA segments) Plasmids, transposons, and viruses are all mobile genetic elements © 2016 Pearson Education, Inc. Viral Diseases in Plants More than 2,000 types of viral diseases of plants are known, accounting for an annual loss of $15 billion worldwide. Damage includes spots on leaves and fruits, stunted growth, and damaged flowers or roots Most plant viruses are RNA viruses Viral infection of plants. Viruses and prions are formidable pathogens in animals and plants Diseases caused by viral infections afflict humans, agricultural crops, and livestock worldwide Smaller, less complex entities known as prions also cause disease in animals © 2016 Pearson Education, Inc. Prions: Proteins as Infectious Agents There are proteins, called prions, that are known to be infectious These appear to cause a number of degenerative brain diseases in various animal species Prions can be transmitted in food Prions act very slowly, with an incubation period of at least 10 years Prions are also virtually indestructable © 2016 Pearson Education, Inc. To date, there is no known cure for prion diseases Prions, according to the leading model, are misfolded forms of proteins normally found in the brain The prion somehow converts the normal proteins to the incorrectly folded form The incorrectly folded form of the proteins forms aggregates that interfere with normal cell functions © 2016 Pearson Education, Inc. Model for how prions propagate Prion New prion Original prion Normal protein Aggregates of prions © 2016 Pearson Education, Inc. You should now be able to: 1. 2. 3. 4. 5. 6. Describe what the virus is made of? Explain why viruses are obligate parasites? Distinguish between the Lytic and Lysogenic cycle Define: a temperate phage and a virulent phage Explain the reproductive cycle of RNA virus Explain the function of reverse transcriptase