Virology Introduction (BIOS5004 Wk1) PDF

Viruses and Virology SARS Foot & mouth disease virus measles Human Virus...

Viruses and Virology SARS Foot & mouth disease virus measles Human Viruses probably infect Immunodeficiency all cellular life… … Virus (human, animal, plant, bacteria, yeast, fungi) Cauliflower mosaic virus Lambda (l) bacteriophage Images: http://www.virology.net/garryfavwebsearch.html Turnip yellow Carter & Saunders Virology: Principles & Applications 2nd edition mosaic virus … … and almost all human cell types eyes, skin, nerves, blood, brain, liver, lungs, gut, genitals  Virus Classification and Taxonomy Classification of viruses is based on various characteristics Molecular composition of the genome Structure of the virus capsid Presence of an envelope; Gene expression strategy (to produce virus proteins) Host range (and possibly cell tropism) Infection pathogenicity https://ictv.global/report Genome sequence similarity and phylogeny  Virus Classification and Taxonomy ICTV – International Committee on the Taxonomy of Viruses The new scope of virus taxonomy: partitioning the virosphere into 15 hierarchical ranks International Committee on Taxonomy of Viruses Executive Committee Nature Microbiology 5:668–674 (2020)  Common misunderstandings about viruses …. Viruses are not cells - they cannot propagate independently - they only propagate inside living cells - they are completely parasitic Viruses are “obligate intracellular parasites” Viruses are not alive - they are inert unless inside a permissive cell Viruses do not grow - each virus has a fixed size - exception = some very small expansion possible in rod or helical viruses Viruses do not divide - viruses duplicate their component biomolecules - new viruses assemble from these molecules - viruses are said to replicate Viruses are not susceptible to antibiotics  Virus have similar components to cells … virus particle or virion PROTEINS GLYCOPROTEINS = tegument or matrix = spikes or peplomers - link capsid & envelope - bind to cell (entry) = nucleocapsid - binds nucleic acid - protects genome MEMBRANE = envelope = capsid - hollow shell - protects genome - binds to cell (entry) GENOME = enzymes - DNA or RNA - carried inside virion or encoded by genome Important differences … NO mitochondria = NO biochemical energy machinery NO ribosomes = NO protein synthesis machinery …  Virus components … virus particle or virion PROTEINS GLYCOPROTEINS = tegument or matrix = spikes or peplomers - link capsid & envelope - bind to cell (entry) = nucleocapsid - binds nucleic acid MEMBRANE - protects genome = envelope = capsid - hollow shell - protects genome GENOME - binds to cell (entry) - DNA or RNA = enzymes - carried inside virion or encoded by genome Virus structural proteins are symmetrically arranged to form capsids rabies virus Ebola virus baculovirus helical rod icosahedral cone polio virus HIV herpesvirus Icosahedral capsids have 20 triangular sides – most appear spherical Symmetrical arrangements of 1, 2, 3 or more types of proteins Papillomavirus Poliovirus Zika virus 2 capsid proteins 4 capsid proteins 1 capsid protein (probably) Herpes viruses* Hepatitis B virus* Human Immunodeficiency virus* 10 capsid proteins 1 capsid protein 1 capsid protein * These examples are enclosed within an outer membrane (envelope)  Helical capsids build hollow cylinders – most use a single protein Many copies of the virus protein (monomer) assemble in a spiral arrangement Typically the virus genome associates intimately with the capsid proteins - structure often referred to as nucleocapsid - variety of lengths, structures seen Tobacco mosaic virus - long, rigid helix Marburg (top) & Ebola (bottom) viruses - highly flexible, often looped Rabies virus - short, bullet-shaped  T4 bacteriophage - combines icosahedral and helical structures head (capsid) region is icosahedral tail region is helical www.bfsc.leidenuniv.nl/images/ellen_fig1.jpg tail has terminal pins and tail fibres micro.magnet.fsu.edu  Viruses have similar components to cells … virus particle or virion PROTEINS GLYCOPROTEINS = tegument or matrix = spikes or peplomers - link capsid & envelope - bind to cell (entry) = nucleocapsid - binds nucleic acid - protects genome MEMBRANE = envelope = capsid - hollow shell - protects genome - binds to cell (entry) GENOME = enzymes - DNA or RNA - carried inside virion or encoded by genome Some viruses have an envelope = a membrane surrounding the capsid Virus glycoproteins are embedded in the virion envelope A virus protein layer links the capsid and envelope This may be a loose association (tegument) or a close-fitting structure (matrix)  Herpesviruses Influenza viruses - multiple glycoproteins - 2 glycoproteins - loose envelope - envelope contains multiple helical nucleocapsids Human immunodeficiency virus Hepatitis B virus - 2 glycoproteins, close envelope - 3 versions of 1 glycoprotein - also some cellular proteins - also forms empty envelope structures virus  Virus genomes … virus particle or virion PROTEINS GLYCOPROTEINS = tegument or matrix = spikes or peplomers - link capsid & envelope - bind to cell (entry) = nucleocapsid - binds nucleic acid - protects genome MEMBRANE = envelope = capsid - hollow shell - protects genome - binds to cell (entry) GENOME = enzymes Virus genomes show diversity in …. - carried inside virion or - size (within limits) encoded by genome - composition (DNA or RNA) (single or multiple “chromosomes”) - conformation (single or double stranded) (circular or linear)) - gene coding strategy (on both or one strand) (positive, negative or ambi-sense) - gene copy number (haploid, merodiploid, diploid)  “SENSE” refers to the nucleotide sequence of a coding region Gene-sense, positive-sense (same as mRNA) Anti-sense, negative-sense It is relevant when considering: - A single gene region in a dsDNA cellular or virus genome - A single gene region in a dsRNA virus genome - The coding strategy of a single-stranded virus genome (ssDNA or ssRNA)  Some virus genomes bind closely with proteins e.g. cellular histones - papillomaviruses, herpesviruses Viral proteins - aid genome structure & function e.g. influenza polymerase and nucleoproteins - twist the ssRNA genome into a dsRNA helix - cut cellular RNA to provide a replication primer e.g. adenovirus terminal protein – serine in C-terminal end has exposed hydroxyl group - acts as primer for DNA genome replication - overcomes the end-replication problem e.g. polio virus VPg protein – allows binding to cell ribosomes (translation)  All virus genomes must contain at least 1 origin of replication (ori) Several varied replication strategies have been identified …. e.g. rolling circle e.g. strand displacement e.g. bidirectional (theta) e.g. unidirectional All viruses must ultimately replicate two complementary nucleic acid strands (even if the genome is single stranded) All virus genomes must contain promoters to regulate gene expression Small virus genomes typically use co-ordinated regulation = several genes regulated by shared promoters e.g. Papillomaviruses, Hepatitis B virus, Human Immunodeficiency virus (HIV) Larger virus genomes can regulate the majority of their genes independently, with most genes having their own promoter e.g. Herpesviruses (Herpes simplex, Cytomegalovirus), Poxviruses (smallpox)  Virus genomes may use unusual sequences for protein synthesis Picornaviruses (e.g. polio virus) - self-complementary sequences at the 5’ end of the RNA genome - Self-anneal into a series of stem-loops = Internal Ribosome Entry Site, IRES - ribosomes bind the RNA even though it has no 5’ cap Retroviruses (e.g. HIV) - self-complementary sequences within gene coding sequences - Self-anneal into a stem loop - stem-loop anneals with adjacent sequence = Pseudoknot - ribosome slips during translation (frame-shift) extending the gene coding capacity Reading for virology content – some suitable textbooks Carter & Saunders (2013) Lostroh (2019) Virology: Principles & Applications Molecular and Cellular Biology 2nd edition of Viruses Wiley Press CRC Press Both of these textbooks are well-laid out and have good content and clarity of writing / explanations, although the newer book has wider concepts in fairly bite-sized chunks that add to the basic concepts and link it to infection. Reading for virology content – reference textbook Howley, Knipe & Whelan Fields Virology Volumes 1 & 2 6th edition (2016) – available in our library Wolters Kluwer 7th edition (2021) Chapter 75 has a section on T4 This is the reference book that professional virologists use. Each chapter is a scientific review written by key researchers. As such it’s acknowledged as the top source book in the field, but the level of detail can be overwhelming. Perhaps save this for if you’re studying a virology aspect for your Project.