Introduction to virology: Viral structure and classification PROF A.O. ABODERIN 11/4/2019 1 History • By the last ½ of 19th C. existence of a diverse world of bacteria, fungi, and protozoa was well established. • 1840 – Jacob Henle hypothesized the concept of submicroscopic agents • 3 major advances – – spontaneous generation did not occur, – R. Koch demonstrated the causes of anthrax and TB, – importance of sterile fields – Lister 11/4/2019 2 Discovery period • Adolf Mayer, a German scientist discovered Tobacco mosaic disease • Dimitri Ivanofsky, a Russian scientist, reported that “the sap of leaves infected with TMD retains its infectious properties even after filtration through Chamberland filters”. Operational definition of viruses • Martinus Beijerinck, a Dutch soil microbiologist showed that the filtered sap could be diluted and then regain its “strength” after replication in living growing tissue of the plant. “contagium 11/4/2019 vivum fluidum” – a contagious living liquid. 3 A new concept • Mayer, Ivanofsky and Beijerinck contibuted to this: – a filterable agent – too small to be observed in the LM – but able to cause disease by multiplying in living cells. • Loeffler and Frosch rapidly described and isolated the first filtrable agent in animals – the foot-and-mouth disease virus. • Walter Reed and his team in Cuba recognized the first human filterable virus, yellow fever 11/4/2019 4 virus in 1900 Virus • The term virus (from the Latin for slimy liquid or poison) • In the first decades of 20th C. the infectious entities were referred to as filterable agents i.e. operational definition • Virus late became restricted to agents that fulfilled the criteria of the trio above and that were the 1st agents to cause a disease that could not be proven using Koch’s postulates 11/4/2019 5 Developments • By the end of 1930s many viruses have been identified – tumour viruses, – bacteriophages, – Mumps virus, – influenza viruses – many arboviruses • The process of developments continues to the present: – human retroviruses, – several new hepatitis viruses and 11/4/2019 – herpesviruses 6 Basic characteristics of Viruses 1- Structure unique: Although viruses are very heterogeneous, there is a unity of structure, basically protein and nucleic acid. 2-Replication: Note, not binary division, but burst of virus particles. 3-Small size: Viruses are "filterable" agents ranging from 20nm – 300nm in diameter. 4-Obligate (genetic) parasites: Dependent on host cell genetic and protein synthesizing machinery. 5-Genome: Virus genome is either DNA or RNA not both. 11/4/2019 7 Control measures for viruses include capitalizing on our knowledge of: Growth on artificial media Division by binary fission Whether they have both DNA and RNA Whether they have ribosomes Their sensitivity to antibiotics Bacteria Yes Yes Yes Yes Yes Mycoplasma Yes Yes Yes Yes Yes Rickettsia No Yes Yes Yes Yes Chlamydia No Yes Yes Yes Yes Viruses No No No No * No 11/4/2019 8 Viral Structure • Characteristics of virus: – Size – Nucleic acid – Metabolic activities • Components of a typical virus – Virion - the intact virus particle – Capsid- The protein coat – Capsomeres – Nucleic acid – Envelope 11/4/2019 9 VIRUS STRUCTURE 1. 2. 3. 4. 5. All viruses are constructed according to certain basic principles. All viruses contain a nucleic acid genome (RNA or DNA) and a protective protein coat (called the capsid). The capsid is made of similar subunits known as the capsomeres. The nucleic acid genome plus the protective protein coat is called the nucleocapsid which may have icosahedral, helical or complex symmetry. In addition, viruses may or may not have an envelope. Viruses range in size from 20-300 nanometers in diameter to several hundred nanometers in length in the case of the filoviridae. 11/4/2019 10 11/4/2019 11 Enveloped virus 11/4/2019 Herpes virus 12 Enveloped virus 11/4/2019 13 Nucleic acid • • • • • Composed of either RNA or DNA Size ranges from 3kb (e.g. hepadna-) to 300kb Encodes from 3-4 to several 100s proteins Single or double stranded, circular or linear RNA genomes comprise either a single molecule of NA or multiple discrete segments • RNA Segments vary from as few as two in Arenaviridae to 12 in Reoviridae • It may have a positive sense or negative sense 11/4/2019 14 The capsid (Virus coat) • Made up of proteins, arranged in multiple almost identical units - capsomeres • Is antigenic and specific for each virus type and so used for virus identification in serological tests. • It protects the viral genome from inactivation by adverse environmental factors and • Helps to determine the symmetry of the virus. • It facilitates attachment and entry of virus into 11/4/2019 15 the cell. Virus symmetry • Repetition of capsid subunits leads to structural arrangements with symmetric features • All but the most complex viruses exhibit either helical or icosahedral symmetry – Helical – repeating protein subunits are bound at regular intervals along a helical spiral formed by NA. All animal viruses with helical symmetry have RNA genomes (B) – Icosahedral – viruses with icosahedral symmetry usually have a spheric shape, with 2-fold, 3-fold, and 5-fold axes of rotational symmetry (A) 11/4/2019 16 Virus symmetry 11/4/2019 17 11/4/2019 18 Icosahedral symmetry 11/4/2019 Adenovirus 19 Virus Taxonomy • Progression in classification Filterable agents – size. Common pathogenic properties, common organ tropisms, and common ecological and transmission properties: e.g. hepatitis viruses, enteroviruses, arboviruses. Since the 1950s Morphologic & physicochemical criteria determine classification More recently – genetic relatedness. There is availability of nucleotide sequences of genomes. 11/4/2019 20 Virus Taxonomy • In the 1950s and 1960s, there was an explosion in the discovery of new viruses • The International Committee on the Nomenclature of Viruses (ICNV) was formed in 1966 and became ICTV in 1973. • ICTV operates under the auspicies of the Virology Division of the International Union of Microbiological Societies. ICTV has 6 committees, 45 study groups and >400 participating virologists 11/4/2019 21 Virus Taxonomy • The 6th report of the ICTV, published in 1995, records a universal taxonomy scheme comprising 1 order, 71 families, 11 subfamilies, and 164 genera, including many floating genera, and more than 4,000 member viruses. • Virus nomenclature does not involve the use of Latinized binomial terms 11/4/2019 22 Criteria for Classification • • • • • Virus classification involves naming and placing viruses into a taxonomic system. Virus classification is based mainly on phenotypic characteristics, including morphology, nucleic acid type, mode of replication, host organisms, and the type of disease they cause. 11/4/2019 23 Current classification • The type and structure of the viral NA and the strategy used in its replication • The type of symmetry of the virus (helical versus icosahedral) • The presence or absence of a lipid envelope 11/4/2019 24 ICTV Classification System Viral classification starts at the level of order and follows as thus, with the taxon suffixes given in italics: • Order (-virales) – Family (-viridae) • Subfamily (-virinae) – Genus (-virus) » Species (-virus) Names of orders and families are italicized. Species names generally take the form of [Disease] Virus. Recognition of orders very recent and deliberately slow; to date, only three have been named, and most families remain unplaced. Approximately 80 families and 4000 species of virus are known. 11/4/2019 25 11/4/2019 29 Virus-Cell Interactions • Viruses require intact cell to replicate • Viruses must disassemble the infecting particle. • Stages in Virus-Cell Interaction – Attachment – Penetration – Disassembly – Transcription 11/4/2019 - Translation - Replication - Assembly - Release 30 Attachment • single capsid components that extend from the virion surface, such as the attachment proteins of adenovirus, reovirus, rotavirus • surface glycoproteins of enveloped viruses such as influenza virus and HIV. • CD4 for HIV I, acetylcholine receptor for rabies virus, or intercellular adhesion molecule I for rhinovirus. 11/4/2019 31 Penetration & Disassembly • Enveloped viruses such as paramyxoviruses and retroviruses enter cells by fusion of the viral envelope with the cell membrane. • Other viruses enter cells by receptormediated endocytosis. • nonenveloped viruses, must traverse cell membranes without a fusion mechanism involving a viral envelope. 11/4/2019 32 Genome Replication • Translation-competent genomes e.g. alphaviruses, flaviviruses & picornaviruses: plus sense, (+)sense • (-)sense RNA genomes paramyxoviruses, orthomyxoviruses & rhabdoviruses • Reoviruses • Retroviruses • DNA viruses except poxviruses replicate in the nucleus 11/4/2019 33 Thank you for listening 11/4/2019 34