Chapter 6 An Introduction to Viruses

The Search for the Elusive Virus Louis Pasteur postulated that rabies was caused by a virus (1884) Ivanovski and Beijerinck showed a disease in tobacco was caused by a virus (1890s) 1950s virology was a multifaceted discipline Viruses: noncellular particles with a definite size, shape, and chemical composition

The Position of Viruses in the Biological Spectrum There is no universal agreement on how and when viruses originated Viruses are considered the most abundant microbes on earth Viruses played a role in the evolution of Bacteria, Archaea, and Eukarya Viruses are obligate intracellular parasites

General Size of Viruses Size range – most <0.2 μm; requires electron microscope

Viral Structure Viruses bear no resemblance to cells Lack protein-synthesizing machinery Viruses contain only the parts needed to invade and control a host cell

General Structure of Viruses Capsids All viruses have capsids (protein coats that enclose and protect their nucleic acid) The capsid together with the nucleic acid is the nucleocapsid Some viruses have an external covering called an envelope; those lacking an envelope are naked Each capsid is made of identical protein subunits called capsomers

General Structure of Viruses Two structural capsid types: Helical - continuous helix of capsomers forming a cylindrical nucleocapsid Icosahedral

General Structure of Viruses Copyright © McGraw-Hill Education. Permission required for reproduction or display. Two structural capsid types: Helical - Icosahedral - 20-sided with 12 corners (a) Capsomers Facet Capsomers Vertex Nucleic acid (b) Capsomers Vertex Fiber (c) 8 (d) © Dr. Linda Stannard, UCT/Photo Researchers, Inc. 8

General Structure of Viruses Viral envelope Mostly animal viruses Acquired when the virus leaves the host cell Exposed proteins on the outside of the envelope, called spikes, are essential for attachment of the virus to the host cell

Functions of Capsid/Envelope Copyright © McGraw-Hill Education. Permission required for reproduction or display. Protects the nucleic acid when the virus is outside of the host cell Helps the virus bind to a cell surface and assists the penetration of the viral DNA or RNA into a suitable host cell Capsomers © Dr. Linda Stannard, UCT/Photo Researchers, Inc. Fred P. Williams, Jr./EPA (a) Envelope Capsid DNA core © Eye of Science/Photo Researchers, Inc. (b)

General Structure of Viruses Complex viruses: atypical viruses Poxviruses lack a typical capsid and are covered by a dense layer of lipoproteins Some bacteriophages have a polyhedral nucleocapsid along with a helical tail and attachment fibers

Types of Viruses

Concept Check: How would you describe this virus? Copyright © McGraw-Hill Education. Permission required for reproduction or display. How would you describe this virus? A. Icosahedral and Naked Helical and Naked Complex and Naked Icosahedral and Enveloped Helical and Enveloped Complex and Enveloped

Concept Check: How would you describe this virus? Copyright © McGraw-Hill Education. Permission required for reproduction or display. How would you describe this virus? A. Icosahedral and Naked Helical and Naked Complex and Naked Icosahedral and Enveloped Helical and Enveloped Complex and Enveloped © Dennis Kunkel/CNRI/Phototake

Nucleic Acids Viral genome – either DNA or RNA but never both Carries genes necessary to invade host cell and redirect cell’s activity to make new viruses Number of genes varies for each type of virus – few to hundreds

Nucleic Acids DNA viruses RNA viruses Usually double stranded (ds) but may be single stranded (ss) Circular or linear RNA viruses Usually single stranded, may be double stranded, may be segmented into separate RNA pieces ssRNA genomes ready for immediate translation are positive-sense RNA ssRNA genomes that must be converted into proper form are negative-sense RNA

General Structure Pre-formed enzymes may be present Polymerases – DNA or RNA Replicases – copy RNA Reverse transcriptase – synthesis of DNA from RNA (AIDS virus)

How Viruses Are Classified Main criteria presently used are structure, chemical composition, and genetic makeup Currently recognized: 3 orders, 63 families, and 263 genera of viruses Family name ends in -viridae, i.e.Herpesviridae Genus name ends in -virus, Simplexvirus Herpes simplex virus I (HSV-I)

Human Viruses & Viral Diseases

Human Viruses & Viral Diseases

Modes of Viral Multiplication General phases in animal virus multiplication cycle: Adsorption – binding of virus to specific molecules on the host cell Penetration – genome enters the host cell Uncoating – the viral nucleic acid is released from the capsid Synthesis – viral components are produced Assembly – new viral particles are constructed Release – assembled viruses are released by budding (exocytosis) or cell lysis

Animal Virus Multiplication

Adsorption and Host Range Virus coincidentally collides with a susceptible host cell and adsorbs specifically to receptor sites on the membrane Spectrum of cells a virus can infect – host range Hepatitis B – human liver cells Poliovirus – primate intestinal and nerve cells Rabies – various cells of many mammals Copyright © McGraw-Hill Education. Permission required for reproduction or display. Envelope spike Host cell membrane Capsid spike Receptor Host cell membrane Receptor (a) (b)

Penetration/Uncoating Flexible cell membrane is penetrated by the whole virus or its nucleic acid by: Endocytosis – entire virus is engulfed and enclosed in a vacuole or vesicle Fusion – envelope merges directly with membrane resulting in nucleocapsid’s entry into cytoplasm

Variety in Penetration and Uncoating

Replication and Protein Production Varies depending on whether the virus is a DNA or RNA virus DNA viruses generally are replicated and assembled in the nucleus RNA viruses generally are replicated and assembled in the cytoplasm Positive-sense RNA contain the message for translation Negative-sense RNA must be converted into positive-sense message

Release Assembled viruses leave the host cell in one of two ways: Budding – exocytosis; nucleocapsid binds to membrane which pinches off and sheds the viruses gradually; cell is not immediately destroyed Lysis – nonenveloped and complex viruses released when cell dies and ruptures Copyright © McGraw-Hill Education. Permission required for reproduction or display. (b) © Chris Bjornberg/Photo Researchers, Inc. Copyright © McGraw-Hill Education. Permission required for reproduction or display. Host cell membrane Viral nucleocapsid Viral glycoprotein spikes Cytoplasm Capsid RNA Budding virion Free infectious virion with envelope Viral matrix protein (a)

Concept Check: Viruses commonly contain both DNA and RNA A. False B. True Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.

Concept Check: Viruses commonly contain both DNA and RNA. True False

Damage to Host Cell Cytopathic effects - virus-induced damage to cells Changes in size and shape Cytoplasmic inclusion bodies Inclusion bodies Cells fuse to form multinucleated cells Cell lysis Alter DNA Transform cells into cancerous cells

Effects of Some Human Viruses

Persistent Infections Persistent infections - cell harbors the virus and is not immediately lysed Can last weeks or host’s lifetime; several can periodically reactivate – chronic latent state Measles virus – may remain hidden in brain cells for many years Herpes simplex virus – cold sores and genital herpes Herpes zoster virus – chickenpox and shingles

Viral Damage Some animal viruses enter the host cell and permanently alter its genetic material resulting in cancer – transformation of the cell Transformed cells have an increased rate of growth, alterations in chromosomes, and the capacity to divide for indefinite time periods resulting in tumors Mammalian viruses capable of initiating tumors are called oncoviruses Papillomavirus – cervical cancer Epstein-Barr virus – Burkitt’s lymphoma

Multiplication Cycle in Bacteriophages Bacteriophages – bacterial viruses (phages) Most widely studied are those that infect Escherichia coli – complex structure, DNA Multiplication goes through similar stages as animal viruses Only the nucleic acid enters the cytoplasm - uncoating is not necessary Release is a result of cell lysis induced by viral enzymes and accumulation of viruses - lytic cycle

Steps in Phage Replication Adsorption – binding of virus to specific molecules on host cell Penetration – genome enters host cell Replication – viral components are produced Assembly – viral components are assembled Maturation – completion of viral formation Lysis & Release – viruses leave the cell to infect other cells 35

Multiplication of Bacteriophage Copyright © McGraw-Hill Education. Permission required for reproduction or display. E. coli host 7 Release of viruses Bacteriophage Bacterial DNA Viral DNA Lysogenic State 1 Adsorption Viral DNA becomes latent as prophage. 2 Penetration 6 Lysis of weakened cell Lytic Cycle DNA splits Spliced viral genome 3 Duplication of phage components; replication of virus genetic material 5 Maturation Viral DNA Bacterial DNA molecule Capsid DNA The lysogenic state in bacteria. The viral DNA molecule is inserted at specific sites on the bacterial chromosome. The viral DNA is duplicated along with the regular genome and can provide adaptive genes for the host bacterium. Tail + Tail fibers 4 Assembly of new virions Sheath Bacteriophage Bacteriophage assembly line. First the capsomers are synthesized by the host cell. A strand of viral nucleic acid is inserted during capsid formation. In final assembly, the prefabricated components fit together into whole parts and finally into the finished viruses.

Comparison of Bacteriophage and Animal Virus Copyright © McGraw-Hill Education. Permission required for reproduction or display. Head Bacterial cell wall Tube Viral nucleic acid Cytoplasm Copyright © McGraw-Hill Education. Permission required for reproduction or display. © K.G. Murti/Visuals Unlimited

Concept Check: Which of the following is a step found in animal virus multiplication but not in bacteriophage replication? Adsorption Penetration Uncoating Assembly Release

Concept Check: Which of the following is a step found in animal virus multiplication but not in bacteriophage replication? Adsorption Penetration Uncoating Assembly Release

Lysogeny: The Silent Virus Infection Not all phages complete the lytic cycle Some DNA phages, called temperate phages, undergo adsorption and penetration but don’t replicate The viral genome inserts into bacterial genome and becomes an inactive prophage – the cell is not lysed Prophage is retained and copied during normal cell division resulting in the transfer of temperate phage genome to all host cell progeny – lysogeny Induction can occur resulting in activation of lysogenic prophage followed by viral replication and cell lysis

Lytic and Lysogenic Lifecycles Copyright © McGraw-Hill Education. Permission required for reproduction or display. E. coli host 7 Release of viruses Bacteriophage Bacterial DNA Viral DNA Lysogenic State 1 Adsorption Viral DNA becomes latent as prophage. 2 Penetration 6 Lysis of weakened cell Lytic Cycle DNA splits Spliced viral genome 3 Duplication of phage components; replication of virus genetic material 5 Maturation Viral DNA Bacterial DNA molecule Capsid DNA The lysogenic state in bacteria. The viral DNA molecule is inserted at specific sites on the bacterial chromosome. The viral DNA is duplicated along with the regular genome and can provide adaptive genes for the host bacterium. Tail + Tail fibers 4 Assembly of new virions Sheath Bacteriophage Bacteriophage assembly line. First the capsomers are synthesized by the host cell. A strand of viral nucleic acid is inserted during capsid formation. In final assembly, the prefabricated components fit together into whole parts and finally into the finished viruses.

Lysogeny Lysogeny results in the spread of the virus without killing the host cell Phage genes in the bacterial chromosome can cause the production of toxins or enzymes that cause pathology – lysogenic conversion Corynebacterium diphtheriae Vibrio cholerae Clostridium botulinum

Techniques in Cultivating and Identifying Animal Viruses Obligate intracellular parasites that require appropriate cells to replicate Methods used: Cell (tissue) cultures – cultured cells grow in sheets that support viral replication and permit observation for cytopathic effects Bird embryos – incubating egg is an ideal system; virus is injected through the shell Live animal inoculation – occasionally used when necessary

Methods for Growing Viruses

Medical Importance of Viruses Viruses are the most common cause of acute infections Several billion viral infections per year Some viruses have high mortality rates Possible connection of viruses to chronic afflictions of unknown cause Viruses are major participants in the earth’s ecosystem

Detection and Treatment of Animal Viral Infections More difficult than other agents Consider overall clinical picture Take appropriate sample Infect cell culture – look for characteristic cytopathic effects Screen for parts of the virus Screen for immune response to virus (antibodies) Antiviral drugs can cause serious side effects

Prions and Other Infectious Particles Prions - misfolded proteins, contain no nucleic acid Extremely resistant to usual sterilization techniques Cause transmissible spongiform encephalopathies – fatal neurodegenerative diseases

Prions Diseases Common in animals: Scrapie in sheep and goats Bovine spongiform encephalopathies (BSE), a.k.a. mad cow disease Wasting disease in elk Humans – Creutzfeldt-Jakob Syndrome (CJS) 48

Other Noncellular Infectious Agents Satellite viruses – dependent on other viruses for replication Adeno-associated virus – replicates only in cells infected with adenovirus Delta agent – naked strand of RNA expressed only in the presence of hepatitis B virus Viroids – short pieces of RNA, no protein coat; only been identified in plants

Concept Check: Exposure to Nucleases that degrade DNA and RNA would damage all of the following EXCEPT Animal Viruses Bacteriophage Prions Satellite Viruses Viroids

Concept Check: Exposure to Nucleases that degrade DNA and RNA would damage all of the following EXCEPT Animal Viruses Bacteriophage Prions Satellite Viruses Viroids