BIOLOGY. Viruses CAMPBELL. Reece Urry Cain Wasserman Minorsky Jackson. Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick TENTH EDITION

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1 CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson 19 Viruses Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick

2 Figure 19.1 Are the viruses (red) budding from this cell alive?

3 Overview: A Borrowed Life Viruses called bacteriophages can infect and set in motion a genetic takeover of bacteria, such as Escherichia coli Viruses lead a kind of borrowed life between life-forms and chemicals The origins of molecular biology lie in early studies of viruses that infect bacteria Viruses were detected indirectly long before they were actually seen

4 The Discovery of Viruses: Scientific Inquiry 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, Wendell Stanley confirmed this hypothesis by crystallizing the infectious particle, now known as tobacco mosaic virus (TMV)

5 Experiment Figure Extracted sap from tobacco plant with tobacco mosaic disease 2 Passed sap through a porcelain filter known to trap bacteria 3 Rubbed filtered sap on healthy tobacco plants 4 Healthy plants became infected

6 Structure of Viruses Viruses are the simplest biological systems. 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 Are viruses living or nonliving? $ --- Viruses cannot reproduce 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.

7 Viral Genomes Viruses genome of may consist of either double-stranded DNA, or single-stranded DNA, or double-stranded RNA,or single-stranded RNA, depending on the kind of virus. A virus is called a DNA virus or an RNA virus, according to the kind of nucleic acid that makes up its genome. The viral genome is usually organized as a single linear or circular molecule of nucleic acid. Viruses have between three and several thousand genes in their genome

8 Capsids and Envelopes A capsid is the protein shell that encloses the viral genome. Capsids are built from protein subunits called capsomeres. A capsid can have various structures. Viruses with Rod-shaped capsidsare called helical viruses. Adenoviruses have 252 identical proteins arranged into a polyhedral capsid with 20 triangular facts an icosahedron. Viruses that infect bacteria -bacteriophages or phages have the most complex capsids. Phages have an elongated capsid head that encloses their DNA and protein tail piece attaches the phage to the host and injects the phage DNA inside. Some viruses have accessory structures viral envelopes to help them infect their hosts. Viral envelope contain host cell phospholipids and membrane proteins as well as proteins and glycoproteins of viral origin A membranous envelope surrounds the capsids of flu viruses.

9 RNA Capsomere DNA Membranous envelope RNA Capsid Head DNA Capsomere of capsid Tail sheath Tail fiber Glycoprotein Glycoproteins nm nm (diameter) nm (diameter) nm 20 nm 50 nm 50 nm 50 nm (a) Tobacco mosaic (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4 virus Figure 19.3 Viral structure

10 Viruses replicate only in host cells Viruses can replicate only within a host cell. An isolated virus is unable to reproduce or do anything else, except infect an appropriate host. An isolated virus is merely a packaged set of genes in transit from one host cell to another. Each type of virus can infect and parasitize only a limited range of host cells, called its host range.

11 General Features of Viral Replicative Cycles Once a viral genome enters a cell (the host), the host 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 self-assemble into new viruses

12 1 Entry and uncoating DNA Capsid VIRUS 3 Transcription and manufacture of capsid proteins 2 Replication HOST CELL Viral DNA mrna Viral DNA Capsid proteins Figure Self-assembly of new virus particles and their exit from the cell

13 Replicative Cycles of Phages Phages are the best understood of all viruses Phages have two reproductive mechanisms: the lytic cycle and the lysogenic cycle

14 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

15 Fig The Lytic Cycle 5 5 Release: Phage enzymes damage the cell Wall, fluid enters the bacteria and it bursts. 1 Attachment: T4 uses its tail fibers 2 Entry of phage DNA and degradation of host DNA Phage assembly 4 Head Tail Tail fibers Assembly: 3 separate sets of proteins form phage heads, tails, and tail fibers. The phage genome is packaged into the capsid as it forms. 3 Synthesis of viral genomes and proteins using host machinery.

16 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 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

17 Figure 19.6 The lytic and lysogenic cycles of phage λ, a temperate phage Phage Phage DNA Tail fiber The phage injects its DNA. Bacterial chromosome Phage DNA circularizes. Daughter cell with prophage Prophage exits chromosome. Many cell divisions create many infected bacteria. The cell lyses, releasing phages. Lytic cycle Lysogenic cycle Prophage Prophage is copied with bacterial chromosome. Phage DNA and proteins are synthesized and assembled. Phage DNA integrates into bacterial chromosome.

18 The lytic and lysogenic cycles Phage DNA The phage attaches to a host cell and injects its DNA. Bacterial chromosome Prophage Lytic cycle Virulent or temperate phage Destruction of host DNA Production of new phages Lysis of host cell causes releases of progeny phages 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

19 Replicative Cycles of Animal Viruses There are two key variables used to classify viruses that infect animals An RNA or DNA genome A single-stranded or double-stranded genome Whereas few bacteriophages have an envelope or an RNA genome, many animal viruses have both

20 Table 19.1

21 Replitive Cycles of Animal Envelope Viruses Most animal viruses with RNA genomes have an envelope. Viruses equipped with an outer glycoprotein envelope use the envelope to enter the host cell. The envelope fuses with the host s membrane, transporting the capsid and the viral genome inside. In the reproductive cycle of an enveloped virus with an RNA genome, viral glycoproteins for new envelopes are made by ribosomes bound to the ER of the host cell, then modified by the host s Golgi apparatus. These glycoproteins are transported to the cell surface, where they wrap themselves in membrane as they bud from the cell. The viral envelope is thus derived from the host s plasma membrane, although viral genes specify some of the molecules in the membrane.

22 Capsid RNA HOST CELL Envelope (with glycoproteins) mrna Template Viral genome (RNA) Glycoproteins ER Capsid proteins Copy of genome (RNA) New virus Figure 19.7 The replicative cycle of an enveloped RNA virus

23 RNA as Viral Genetic Material In some viruses with single-stranded RNA (class IV), the genome acts as mrna and is translated into viral protein immediately after infection. In others (class V), the RNA genome serves as a template for complementary RNA strands, which function both as mrna and as templates for the synthesis of additional copies of genome RNA. All viruses that require RNA RNA synthesis to make mrna use a viral enzyme that is packaged with the genome inside the capsid. Retroviruses (class VI) have the most complicated life cycles. Retroviruses carry an enzyme called reverse transcriptase that transcribes DNA from an RNA template. This provides RNA DNA information flow.

24 HIV is a Retrovirus HIV (human immunodeficiency virus) is the retrovirus that causes AIDS (acquired immunodeficiency syndrome) HIV and other retroviruses are enveloped viruses that contain two identical molecules of single-stranded RNA and two molecules of reverse transcriptase. The reproductive cycle of HIV illustrates the pattern of infection and replication in a retrovirus. After HIV enters the host cell, reverse transcriptase molecules are released into the cytoplasm and catalyze the synthesis of viral DNA. The newly made viral DNA enters the cell s nucleus and is inserted as a permanent provirus into a chromosome. The host s RNA polymerase transcribes the proviral DNA into RNA molecules that can function both as mrna for the synthesis of viral proteins and as genomes for new virus particles released from the cell.

25 Glycoprotein Viral envelope Capsid Life Cycle of HIV HIV Membrane of white blood cell Reverse transcriptase HIV RNA (two identical strands) Viral RNA HOST CELL Reverse transcriptase RNA-DNA hybrid DNA RNA genome for the next viral generation Chromosomal DNA NUCLEUS Provirus mrna 0.25 µm HIV entering a cell New virus Figure 19.8 New HIV leaving a cell

26 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 Avirus particles released from the cell

27 Evolution of Viruses Viruses do not fit our definition of living organisms Since viruses can reproduce only within cells, they probably evolved as bits of cellular nucleic acid 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 Mimivirus, a double-stranded DNA virus, is the largest virus yet discovered There is controversy about whether this virus evolved before or after cells

28 Viruses, viroids, and prions are formidable pathogens in animals and plants Diseases caused by viral infections affect humans, agricultural crops, and livestock worldwide. Smaller, less complex entities called viroids and prions also cause disease in plants and animals, respectively Some viruses damage or kill cells by triggering the release of hydrolytic enzymes from lysosomes. Some viruses cause the infected cell to produce toxins that lead to disease symptoms. Others viruses have molecular components, such as envelope proteins, that are toxic. In some cases, viral damage is easily repaired (respiratory epithelium after a cold), but in others, infection causes permanent damage (nerve cells after polio). Many of the temporary symptoms associated with a viral infection result from the body s own efforts at defending itself against infection.

29 The Immune System The immune system is the body s natural defense mechanism against viral and other infections. Vaccines are harmless variants or derivatives of pathogenic microbes, that stimulate the immune system to mount defenses against the actual pathogen. Vaccines can prevent certain viral illnesses. Vaccination has eradicated smallpox. Effective vaccines are available against polio, measles, rubella, mumps, hepatitis B, and a number of other viral diseases. Antiviral drugs can help to treat, though not cure, viral infections. Viral infections cannot be treated by antibiotics. Most antiviral drugs resemble nucleosides and interfere with viral nucleic acid synthesis.

30 Emerging new Viruses The emergence of these new viral diseases is due to three processes: mutation; the dissemination of a viral disease from a small, isolated population; and the spread of existing viruses from one species to another. RNA viruses tend to have high mutation rates because replication of their nucleic acid lacks proofreading. Some mutations create new viral strains with sufficient genetic differences from earlier strains that they can infect individuals who had acquired immunity to these earlier strains. Flu epidemics are caused by new strains of influenza virus to which people have little immunity. H1N1 virus of Influenza outbreak from Mexico recently. These strains can cause pandemics, global epidemics. The avian flu is a virus that recently appeared in humans and originated in wild birds Emerging viruses are those that appear suddenly or suddenly come to the attention of scientists like Severe acute respiratory syndrome (SARS) recently appeared in China.

31 Figure µm (a) 2009 pandemic H1N1 influenza A virus (b) 2009 pandemic screening (c) 1918 flu pandemic

32 Dissemination of viral disease A viral disease can spread from a small, isolated population to become a widespread epidemic. For example, AIDS went unnamed and virtually unnoticed for decades before spreading around the world. Technological and social factors, including affordable international travel, blood transfusion technology, sexual promiscuity, and the abuse of intravenous drugs, allowed a previously rare disease to become a global scourge.

33 Viral spread between species A third source of new viral diseases is the spread of existing viruses from one host species to another. It is estimated that about three-quarters of new human diseases originated in other animals. For example, a species of bat has been identified as the likely natural initiator of the SARS virus.

34 Flu epidemics illustrate the effects of viruses moving between species There are three types of influenza virus: Types B and C- infect only humans and have never caused an epidemic Type A- which infects a range of animals. Influenza A strains have caused three major flu epidemics among humans in the last 100 years. The worst was the Spanish flu pandemic of , which killed 40 million people. This strain probably originated in birds and then passed between different species, undergoing mutations. In animals infected with multiple strains of flu virus, the different strains underwent genetic recombination, leading to the emergence of a virus capable of infecting human cells. Humans lacked immunity to this novel, virulent recombinant virus.

35 Viral Diseases in Plants Figure More than 2,000 types of viral diseases of plants are known and cause spots on leaves and fruits, stunted growth, and damaged flowers or roots Most plant viruses have an RNA genome Viruses can spread from one plant cell to another through plasmodesmata. Plant viruses spread disease in two major modes: Horizontal transmission, entering through damaged cell walls Vertical transmission, inheriting the virus from a parent

36 Viroids and Prions: The Simplest Infectious Agents Viroids are circular RNA molecules that infect plants and disrupt their growth. These small RNA molecules can disrupt plant metabolism and stunt plant growth, perhaps by causing errors in the regulatory systems that control plant growth. Viroids show that a single molecule can act as an infectious agent to spread disease. Viroids are small circular RNA molecules that infect plants and disrupt their growth.

37 Prions are infectious proteins that spread disease Prions are slow-acting (10 year onset), virtually indestructible infectious proteins that cause brain diseases in mammals Prions propagate by converting normal proteins into the prion version Scrapie in sheep, mad cow disease, and Creutzfeldt- Jakob disease in humans are all caused by prions Prions are likely transmitted in food. Prions are virtually indestructible. They are not destroyed or deactivated by heating to normal cooking temperatures. There is no known cure for prion diseases.

38 How can a protein be a transmissible pathogen? Fig How prions (probably) propagate: 1. Prions are just misfolded normal proteins. 2. When a prion comes in contact with a normally folded protein, it might induce that protein to fold into the same abnormal shape. 3. $ --- Aggregates of misfolded (prion) protiens may just cause brain cells to be disfunctional and eventually brain degeneration will occur.

39 H1N1 flu vaccination Figure 19.UN01c