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11/15/2011 Chapter 19 - Viruses Outline I. Viruses A. B. C. D. Structure of viruses Common Characteristics of Viruses Viral replication HIV II. Prions Copyright © 2009 Pearson Education, Inc. The Good the Bad and the Ugly Structural Features and Characteristics Non cellular, viral particles = virions Viruses – fit into the bad category Virions are very small Viruses are not like other living organisms. They are acellular, which means they don’t have their own cells – they hijack other cells and use them to reproduce themselves. Viruses may remain inactive or latent in the host for many years. Viruses lack ribosomes Copyright © 2009 Pearson Education, Inc. Structural Features and Characteristics Copyright © 2009 Pearson Education, Inc. Viral Genomes Viruses usually have: Viral genomes may consist of either 1. Genetic material (DNA or RNA) 2. Protein coat = capsid (helix or icosahedral) 3. Some may have a fatty membrane = envelope Copyright © 2009 Pearson Education, Inc. 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 © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, 1 11/15/2011 Fig. 27.1 Figure 19.3 capsid RNA DNA Membranous RNA envelope Capsid DNA Head Tail sheath capsid Tail fiber Glycoprotein 18 250 nm (a) Tobacco mosaic virus Copyright © 2009 Pearson Education, Inc. Viruses vary in size, as well as in shape 20 nm Glycoproteins 70–90 nm (diameter) 80–200 nm (diameter) 80 225 nm 50 nm (b) Adenoviruses 50 nm (c) Influenza viruses 50 nm (d) Bacteriophage T4 Copyright © 2009 Pearson Education, Inc. Bacteriophage Virus Copyright © 2009 Pearson Education, Inc. Figure 19.1 0.5 mm Copyright © 2009 Pearson Education, Inc. 2 11/15/2011 Corona Virus Responsible for SARS epidemic in 2003 Characteristics of Living Organisms Are Viruses Alive? 1. Contain biological molecules including: Proteins, nucleic acids, carbohydrates and lipids 2. Cellular 3. Reproduce 4. Acquire and use energy - Metabolism 5. Growth and Development 6. Respond to environment 7. Maintain Homeostasis 8. Populations of living organisms evolve and have adaptive traits They are acellular Copyright © 2009 Pearson Education, Inc. Types of viruses - Retrovirus Retroviruses – contain RNA and an enzyme reverse transcriptase. They can’t perform metabolic activity and reproduction without a host Contains either DNA or RNA Do not contain ribosomes, lack the enzymes needed to transcribe DNA Copyright © 2009 Pearson Education, Inc. Types of viruses Bacteriophages – viruses that infect bacteria Reverse transcriptase turns RNA into DNA Copyright © 2009 Pearson Education, Inc. Copyright © 2009 Pearson Education, Inc. 3 11/15/2011 DNA VIRUS Figure 19.4 1 Entry and uncoating 3 Transcription and manufacture of capsid proteins Capsid 2 Replication HOST CELL Viral DNA mRNA Viral DNA 4 Self-assembly of new virus particles and their exit from the cell Animation: Simplified Viral Reproductive Cycle Right-click slide / select “Play” © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, Capsid proteins Copyright © 2009 Pearson Education, Inc. Replicative Cycles of Phages Phages have two reproductive mechanisms: the lytic cycle and the lysogenic cycle The Lytic Cycle The lytic cycle is a phage replicative cycle that culminates in the death of the host cell The lytic cycle produces new phages and lyses (breaks open) 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 © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, Figure 19.5-1 1 Attachment Animation: Phage T4 Lytic Cycle Right-click slide / select “Play” © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, Copyright © 2009 Pearson Education, Inc. 4 11/15/2011 Figure 19.5-2 Figure 19.5-3 1 Attachment 1 Attachment 2 Entry of phage DNA and degradation of host DNA 2 Entry of phage DNA and degradation of host DNA 3 Synthesis of viral genomes and proteins Copyright © 2009 Pearson Education, Inc. Copyright © 2009 Pearson Education, Inc. Figure 19.5-4 Figure 19.5-5 1 Attachment 1 Attachment 2 Entry of phage DNA and degradation of host DNA Phage assembly Tail Release Phage assembly 4 Assembly Head 5 2 Entry of phage DNA and degradation of host DNA Tail fibers 3 Synthesis of viral genomes and proteins Copyright © 2009 Pearson Education, Inc. 4 Assembly Head Tail Tail fibers 3 Synthesis of viral genomes and proteins Copyright © 2009 Pearson Education, Inc. Steps in lytic cycle 1. Attach to a host cell 2. Penetrate host cell – the genetic material must enter the host cell, capsid may remain on outside 3. Virus cuts host DNA into pieces 4. Uses host cell for protein synthesis 5. Assemble new viral particles 6. Lysis - Release by rupturing host cell. Some virus do not lyse host cell, instead they bud off. Copyright © 2009 Pearson Education, Inc. 0.25 µm Copyright © 2009 Pearson Education, Inc. 5 11/15/2011 Lysogenic cycle The Lysogenic Cycle Some viruses don’t immediately kill their hosts They integrate their DNA into the host DNA When the viral DNA is integrated into the host DNA, the genetic material it is called a prophage, the infected cell is the lysogen Induction: The virus will switch to the lytic phase 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 © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, Copyright © 2009 Pearson Education, Inc. Daughter cell with prophage Figure 19.6b Cell divisions produce a population of bacteria infected with the prophage. Phage DNA circularizes. Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Lysogenic cycle Certain factors determine whether lysogenic cycle lytic cycle or Prophage is entered is induced Phage DNA integrates into the bacterial chromosome, becoming a prophage. Animation: Phage Lambda Lysogenic and Lytic Cycles Right-click slide / select “Play” © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, Figure 19.6a Phage DNA The bacterium reproduces, copying the prophage and transmitting it to daughter cells. Copyright © 2009 Pearson Education, Inc. Replicative Cycles of Animal Viruses The phage injects its DNA. Phage DNA circularizes. Phage Bacterial chromosome There are two key variables used to classify viruses that infect animals DNA or RNA? Single-stranded or double-stranded? Lytic cycle The cell lyses, releasing phages. Certain factors determine whether lysogenic cycle lytic cycle or is entered is induced New phage DNA and proteins are synthesized and assembled into phages. Copyright © 2009 Pearson Education, Inc. © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, 6 11/15/2011 Figure 19.7 Retroviruses Capsid Capsid and viral genome enter the cell RNA Envelope (with glycoproteins) Retroviruses have RNA which gets changed to a a double stranded DNA HOST CELL Template Viral genome (RNA) mRNA Retroviruses have an enzyme called reverse transcriptase to do this ER HIV is a retrovirus, HIV uses the lysogenic cycle then switches to the lytic cycle Capsid proteins Copy of genome (RNA) Glycoproteins New virus Copyright © 2009 Pearson Education, Inc. Figure 19.8a Copyright © 2009 Pearson Education, Inc. Glycoprotein Figure 19.8b Viral envelope Capsid RNA (two identical strands) Reverse transcriptase HOST CELL HIV Viral RNA HIV Membrane of white blood cell Reverse transcriptase RNA-DNA hybrid DNA Chromosomal DNA RNA genome for the next viral generation NUCLEUS Provirus mRNA 0.25 m HIV entering a cell New virus Copyright © 2009 Pearson Education, Inc. New HIV leaving a cell Copyright © 2009 Pearson Education, Inc. Steps in HIV Virus Replication 1. Attach to a host cell = helper T Cell (CD4 cells) HIV envelope has gp120 fits CD4 receptor on T cell Then binds with coreceptor ie CCR5 2. Penetrate host cell using endocytosis 3. Viral RNA is turned into viral DNA Using the enzyme reverse transcriptase 4. Integrate the viral DNA into the host Animation: HIV Reproductive Cycle Using the enzyme integrase Right-click slide / select “Play” © 2011©Pearson Education, Inc.Inc. Copyright 2009 Pearson Education, Copyright © 2009 Pearson Education, Inc. 7 11/15/2011 Steps in HIV Virus Replication Fig. 27.6 5. Transcribe the integrated viral DNA to make viral mRNA 6. Protein synthesis 7. Assemble new viral particles Using the enzyme protease 8. Release, using exocytosis Copyright © 2009 Pearson Education, Inc. HIV Human Immunodeficiency Virus: Cause AIDS HIV is a particularly devastating virus because it attacks the hosts immune system The human immune system has T cells to protect us against foreign bodies like viruses and bacteria. T cells have receptors on their surface that recognize foreign vs our own cells Copyright © 2009 Pearson Education, Inc. HIV Infection Reverse transcriptase does the opposite of RNA polymerase: It turns RNA into a double stranded DNA molecule Integrase puts this viral DNA into the T cell’s DNA For a period of time the DNA may not produce any protein but if the host cell replicates then the viral DNA is also replicated Copyright © 2009 Pearson Education, Inc. Copyright © 2009 Pearson Education, Inc. HIV Infection HIV receptors on the surface of the envelope bind with the receptors CD4 and coreceptor CCR5) on the T cells, penetrated host cell Protein coat (capsid) dissolves HIV has three main enzymes: Integrase, reverse transcriptase and protease Copyright © 2009 Pearson Education, Inc. HIV Infection Eventually the viral DNA in the host cell will begin to make proteins needed to make new HIV Proteases help package the new virus components into a new envelope using the host cell membrane The new viruses are released from the host to infect other cells Copyright © 2009 Pearson Education, Inc. 8 11/15/2011 HIV Treatments There is no cure. These treatments can slow the spread of the virus in the body but not completely get rid of it There are three main targets to fight HIV: 1. Reverse Transcriptase Inhibitors AZT anti-viral drug AZT is a reverse transcriptase inhibitor. It also inhibits DNA polymerase but has 100 – 300 X greater affinity for reverse transcriptase AZT is a thymidine analog Bind to and disable reverse transcriptase 2. Protease Inhibitors 3. Fusion Inhibitors - prevent HIV entry into cells. Copyright © 2009 Pearson Education, Inc. HIV in the US In 2009 there were an estimated 48,100 new HIV infections in the US 1.2 million people in the United States are living with HIV infection and 1 in 5 are unaware of their infection. More than 16,000 people with AIDS were estimated to have died in 2008, and nearly 594,500 people with AIDS in the US have died since the epidemic began. Influenza Virus In 1918 – 1919 influenza killed 20 - 50 million people, more than the numbers of soldiers in WWI The type of influenza that causes the most problem infects both bird, swine and human hosts Influenza virus capsid covered with envelope with protein spikes. Different strains have different types of proteins. Copyright © 2009 Pearson Education, Inc. In 2007, an estimated 33 million people worldwide ( 2.5 million children) were living with HIV/AIDS. Approximately two-thirds of these people live in Sub-Saharan Africa; another 20 percent live in Asia and the Pacific. More than 25 million people with HIV/AIDS have died since the first AIDS cases were identified in 1981. In 2007 alone, HIV/AIDS-associated illnesses caused the deaths of approximately 2.1 million people worldwide (330,000 children) Hantavirus The hantavirus causes pneumonia Hosts include deer mice (peromyscus) and humans Transmitted through respiratory exposure to rodent fecal droppings and urine Copyright © 2009 Pearson Education, Inc. 9 11/15/2011 Ebola virus Viruses can cause cancer Ebola virus causes severe hemorrhagic fever Natural host unknown Death rates 50 – 90% of those infected Copyright © 2009 Pearson Education, Inc. Hepatitis B infection – liver cancer Papilloma virus – cervical cancer Copyright © 2009 Pearson Education, Inc. Prions A similar disease is Scabies in sheep Mad Cow Disease, Kuru and Creutzfelt-Jakob diseases are all caused by prions Prions are abnormal proteins, they are not as soluble as the normal proteins. The normal protein is needed for nerve cells to operate properly Prions are able to convert normal proteins into more abnormal proteins The abnormal proteins coagulate in the brain causing transmissible spongiform encephalopathies (TSEs) Copyright © 2009 Pearson Education, Inc. In England infected sheep were fed to cows, leading to an outbreak of mad cow disease Humans ate the infected cow meat and some people have contracted mad cow disease – the estimates of how many people vary widely To contract mad cow disease you need to eat the part of the cow that is contaminated: brain or spinal tissue. Copyright © 2009 Pearson Education, Inc. Figure 19.11 Important Concepts Know the vocabulary in the lecture Prion Normal protein Structural features and characteristics of viruses, what are common shapes of the caspids Original prion New prion Aggregates of prions Steps in a virus replication both lysogenic cycle and lytic cycle Be able to describe in detail the steps of HIV infection of T Cells What are retroviruses and what enzyme do they have Copyright © 2009 Pearson Education, Inc. Copyright © 2009 Pearson Education, Inc. 10 11/15/2011 Important Concepts What three enzymes does HIV have, what are their functions What cells are the host cell of HIV What are the main targets of HIV drugs Examples of viruses given in class and their hosts Know the examples of viruses that cause cancer, and what cancers they cause. Prions – what are they, what diseases are associated with them Copyright © 2009 Pearson Education, Inc. 11