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Outline Viruses The Discovery of Viruses The Nature & Structure of Viruses Bacteriophages Disease Viruses Virus Reproduction AIDS Virus Therapies Emerging Viruses Viruses and cancer Prions 1 Discovery of Viruses 1892 Russian Dmitri Ivanovski Could not filter disease agents causing Tobacco mosaic disease. 1898 Dutch botanist, Martinus Biejerinck “kills’ tobacco mosaic disease agent at 90C. 1935 - Wendell Stanley isolated and crystallized the Tobacco Mosaic Virus Nature of Viruses 1. Agents of Disease found in virtually all organisms host range usually specific 2. No cell organization 3. No Metabolism 4. No organelles 5. Cannot reproduce independent of cells 6. Set of genetic instructions 7. Renegade nucleic acid coated with protein 1 Virus Structure Nature of Viruses 1. Nucleic Acid Core All viruses have same basic structure (1) Nucleic acid core – DNA or RNA Double-stranded – most DNA viruses Single-stranded – most RNA viruses Bacteriophage (2) Capsid – protein envelope around nucleic acid core 2. Protein Capsid HIV (3) Envelope – membrane-like 3. Envelope (4) Specialized enzymes inside capsid Phospholipid bilayer Proteins Glycoproteins 5 SARS Virus Genome SARS virus Severe acute respiratory syndrome 1. RNA Virus 2. 29,751 nucleotides 3. Six encoding genes make 2 Replicases Spike proteins Envelope glycoproteins Membrane glycoprotein Nucleocapsid protein Viruses come in a variety of shapes Helical - Tobacco mosaic Icosahedral – Adenovirus Complex - Bacteriophage Viral genome of E. coli bacteriophage 48,502 nucleotides 23 proteins Æ development & maturation Other enzymes Æ integrate virus DNA into host genome 2 Viral Genome Structure Viruses vary in size, as well as in shape 1. DNA Viruses Æ have Double-Stranded DNA Varicella zoster (Chicken pox) Herpes simplex (Herpes) Epstein-Barr (Mononucleosis) 2. RNA Viruses Æ have Single Stranded RNA (+) Stranded RNA Æ RNA = mRNA HIV (AIDS) Enterovirus (Polio) (-) Stranded RNA Æ RNA bases complimentary to mRNA Influenza (flu) Rhabdovirus (rabies) 9 Virus Replication 1) Virions - viruses outside cells metabolically inert Virus Replication – Lytic Cycle Entry Adsorption 2) Viruses are obligate intracellular parasites -Host range = Suitable cells for a virus -Tissue tropism = Types of cells infected Rabies virus Æ neurons Hepatitis virus Æ liver cells 3) Virus hijacks cell transcription & translation machinery 4) Viruses can remain dormant or latent for years Chicken pox Æ children Shingles Æ Adults Synthesis Release Assembly 3 Virus Replication – Lytic Cycle Bacteriophage Replication – Lytic Cycle Prophage - Adsorption = Viral attachment - Entry = Viral entry - Synthesis = Viral components are made - Assembly = Components are put together - Release = Viral exit Lysogenic Cycle 13 Bacteriophage Replication – Lysogenic Cycle - Adsorption = Viral attachment - Entry = Viral entry Induction Æ Prophage exits 14 genome and enters lytic cycle Virus Replication – Two Cycles -Lytic cycle = Virus kills the host cell -Lysogenic cycle = Virus incorporates into the cell’s genome INTEGRATION INDUCTION Lytic phage are called virulent - Synthesis = Viral components are made - Assembly = Components are put together - Release = Viral exit Lysogenic phage are called temperate 15 16 4 HIV and AIDS • HIV = Human Immunodeficiency Virus • AIDS = Acquired immune deficiency syndrome Immune Response 4. B Cells produce Antibodies 3. Cytotoxic T Cell 1. Macrophage 5. Memory B Cells 2. Helper T Cell Helper T Cells activated by Antigenpresenting Macrophages Fig. 26.2c(TE Art) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. gp120 glycoprotein Human immunodeficiency virus (HIV) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. gp120 glycoprotein HIV Infection HIV 2.HIV enters cell by endocytosis. Envelope 1. HIV Attachment to CD4 & CCR5 Host cell DNA Capsid 3. Reverse Transcriptase Makes DNA 4. Virus DNA integrates Into DNA of host cell Enzyme RNA 6. Virus exits macrophage by exocytosis 5. Transcription of virus DNA produces RNA to be translated. 5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mutated HIV gp120 glycoprotein Helper T Cell CD4 receptor CXCR4 Coreceptor specific to T cells HIV Infection 2.HIV enters cell by endocytosis. 1. HIV attachment 3. Reverse Transcriptase Makes DNA Host Cell DNA HIV Replication 4. Virus DNA integrates Into host cell DNA 6. Virus exits by cell lysis 5. Transcription of virus DNA produces RNA to be translated or serve as viral genome. HIV & Disease Evolution HIV Therapies 1. Combination Therapy – Synthetic drugs Block Virus Replication Block Viral Protein Synthesis 2. Vaccine – Introduce defective gene (nef) 3. Blocking entry of virus into cell Chemokines block entry Mutated coreceptors (CCR5) 4. Blocking RNA replication Naturally occuring Cell Antiviral factor blocks virus replication 23 6 Vaccine Influenza Viruses Types of Flu Virus: Different Capsid Protein Type A, B & C… Type A Æ serious epidemics in humans Type B & C Æ mild human infections Subtypes of Flu Virus = Strains Different Envelope proteins (protein spikes) Hemaglutinin “H”– gets virus in cell. Neuraminidase “N”– gets virus out. Emerging Viruses Emerging Viruses Deer mouse hantavirus hemorrhagic-type infection Highly fatal Ebola virus hemorragic virus ≈ 90% fatal SARS virus: respiratory infection ≈ 8% fatal 1. Stimulates production of antibodies. 2. Why a new flu vaccine every year? Viral H and N genes are highly variable 1. mutation 2. recombination. Example Type A flu virus: 13 “H” Subtypes 9 “N” Subtypes Pandemic = global infections 1918 A(H1N1) killed 40 million people 1957 A(H2N2) killed 100,000 Americans 1968 A(H3N2) killed 70,000 Americans (infected 50 million) Emerging Viruses SARS -Severe acute respiratory syndrome -Caused by a coronavirus -Host is civets -RNA genome contains six main genes -SARS vaccines currently being developed 28 7 Viruses and Cancer Prions Viruses may contribute to about 15% of all human cancers Viruses can cause cancer by altering the growth properties of human cells -1. Triggering expression of oncogenes -2. Disrupting tumor-suppressor genes In June 2006, the FDA approved the use of a new HPV vaccine to prevent cervical cancer “Proteinaceous infectious particles” Cause transmissible spongiform encephalopathies (TSEs) -Mad cow disease -Scrapie in sheep -Creutzfeldt-Jacob disease in humans Animals have normal prion proteins (PrPc) -Misfolded proteins (PrPsc) cause disease 29 30 END 31 8