Viral Classification and Structure PDF

Viral Classification Biomedical Science III Virology (MVI3MV1) Department of Virology 2025 Lunga Xaba Re-cap Properties of Viruses 1. DNA/RNA (Bad news) surrounded by a protein coat (capsid) and have a nucleic acid core comprising DNA or RNA. 2.(may be) enclosed i...

Viral Classification Biomedical Science III Virology (MVI3MV1) Department of Virology 2025 Lunga Xaba Re-cap Properties of Viruses 1. DNA/RNA (Bad news) surrounded by a protein coat (capsid) and have a nucleic acid core comprising DNA or RNA. 2.(may be) enclosed in a protective envelope 3. viruses do not grow, neither respire nor metabolize. They lack organelles 4.OBLIGATE INTRACELLULAR PARASITES Inactive outside of host cells, only become active within host cells. Once in host protein coat dissembles allowing for replication, assembly and release. reproduce only within the host cells  Overview History & Rationale ICTV Classification Properties Hierarchy Nomenclature Baltimore Classification Learning goals The rationale for a classification system Know the two classification systems ICTV and Baltimore The nomenclature used for the ICTV classification (eg. Order (virales), family ( viridae), subfamily (virinae) 7 groups Baltimore classification Be able to draw a diagram  History of taxonomy Initially, There was no system and haphazard naming E.g. According to the disease – rabies, hepatitis viruses E.g. according to the cause – influenza E.g. According to the body site – rhinovirus E.g. According to the area it was discovered – Rift Valley fever virus E.g. According to the person who discovered it - Epstein-Barr virus (EBV) History of taxonomy Then, in the 60s Advent of electron microscopy Deciphered more information about viruses – e.g. structure, shape, composition Realized the complexity and diversity of them They don’t fit neatly into existing classification systems for cellular organisms A new hierarchical system was developed Nature of the nucleic acid in the virion Symmetry of the protein shell Presence or absence of a lipid membrane Dimensions of the virion and capsid  History of taxonomy Then, in the 70s Advent of sequencing technologies Genomics started to play a role in taxonomy The classification therefore needed adjusting and reclassifying We developed the International Committee on the Taxonomy of Viruses (ICTV) to handle this task. Simultaneously, David Baltimore developed an alternative classification Baltimore Classification Based on type of genome, and how it replicates.  Taxonomy concepts Monothetic system Based on a single characteristic or a series of single characteristics. Good for plants and animals. The characteristics are both Lends itself to necessary and sufficient in order to hierarchy identify members of a category Polythetic system Good for viruses, as Akin to family resemblance it accounts for Criteria are neither necessary nor various properties sufficient simultaneously There is a set of criteria. A minimum number of criteria must be satisfied. No single criterion is essential.  ICTV ICTV( International Committee on Taxonomy of Viruses) deals with viral species in a polythetic fashion Requires consideration of various properties of viruses A group of virologists rationalise assignment properties to groups of viruses The system has to evolve over time as more information becomes availible  Virus species Lowest taxon in the hierarchy of classification First formally defined in 2000: a polythetic class of viruses that constitute a replicating lineage and occupy a particular ecological niche Example: polythetic class Genome relatedness Tropism Antigenic properties members have several properties in common Mode of transmission But they do not necessarily all share a single common defining property differ from the higher viral taxa, which are “universal” classes and as such are defined by properties that are necessary for membership Virus species Viruses (including virus isolates, strains, variants, types, sub-types, serotypes, etc.) should wherever possible be assigned as members of the appropriate virus species, although many viruses remain unassigned because they are inadequately characterized. All virus species must be represented by at least one virus isolate. s Genera, Families, Orders Almost all virus species are Distinguishing properties: members of recognized genera Virus morphology Genome organization Some genera are members of Method of replication Size of proteins recognized sub-families All sub-families and most genera are members of recognized HIERARCHY LEVELS: families. An Order is the highest (Order) Family taxonomic level into which (Sub-family) viruses can be classified Genus Species Some families are members of recognized orders: Nidovirales, Mononegavirales, Herpesvirales  Nomenclature NB: Suffixes are given for the various taxa Taxon Suffix Order -virales Family -viridae Subfamily -virinae Genus -virus Specie No specific suffix Rules Taxa should be capitalized Written in Italics Preceded by the name of the taxon Species First word should not be capitalized, unless there are proper nouns Examples Formal description of human respiratory syncytial virus: This virus belongs to the order Mononegavirales, family Paramyxoviridae, subfamily Pneumovirinae, genus Pneumovirus, species Human respiratory syncytial virus. Virologists may use more informal names for some of the viruses, example herpesvirus = any member of the family Herpesviridae Baltimore Classification DNA —> RNA —> protein Based on Nature of genome (DNA vs RNA) Polarity of genome (positive vs negative sense) Reverse transcription (Yes or no) Based on the nature of the pathway from nucleic acid to mRNA synthesis 7 categories Groups 1&2 : DNA, replicates via DdDp Group 3 : dsRNA, replicates in cytoplasm Groups 4&5 : ssRNA, polarity of the genome Group 6 : +sense RNA viruses that replicate via a DNA intermediate Group 7: dsDNA viruses that replicate via a ssRNA intermediate FIGURE 2.. The Baltimore classification, a vims classification scheme based on the form ,of' nucleic acid present in virion particles and the pathway- for expression of the genetic material as rness,en,ger RNA.1The orig inal schemecontained groups I t hro1UghVI and has be,en expanded to accnmmodate DNA- containing, mversetranscribingviruses. Virus taxonomy The advent of nucleotide sequence determination has revolutionized biology and largely rationalized taxonomy The universal virus taxonomy provides a classification scheme that is supported by verifiable data and expert consensus. It is an indispensable framework both for further study of the currently recognized virus species and for the identification and characterization of newly emergent viruses Overview Principles viral Structure Nomenclature in virus structure Functions of a virion Methods of studying viral structure Capsid symmetry Helical Symmetry Icosahedral symmetry Self assembly Viruses with envelopes Viral Structure Biomedical Science III Virology (MVI3MV1) Department of Virology 2025 Learning goals Understand virus structure Be able to draw and label a diagram of an enveloped virus Definition of viral structure nomenclature Function of the structural proteins in relation to the function of the virion Understand the principle of the methods used to identify or study viral structure Structural difference between enveloped vs non- enveloped viruses and how this impacts other biological properties Viral Structure Nomenclature used in virus structure Term Synonym Definition Subunit Single, folded polypeptide chain Structural unit Unit from which capsid or nucleocapsid are built (maybe made up of one or more protein subunits Capsid Coat Protein shell surrounding the viral nucleic acid Nucleocapsid Core Nucleic acid-protein assembly packaged within the virion Envelope Viral Membrane Host cell-derived lipid bilayer with viral glycoproteins Virion Viral particle Infectious viral particle Principles of viral structure Viral particles (virions) are made up of structural proteins and nonstructural components including enzymes, small RNAs(sRNAs) and cellular macromolecules Primary function of a virion: ▪ Protect viral genome ▪ Effective transmission of viral genome from one host cell to another Viral particles (virions) are designed to protect the viral genome Genetic economy dictates the construction of capsids from small subunits Virus particles are metastable structures Functions of virion proteins Protection of the Genome Assembly of stable protective protein shell Specific recognition and packaging of nucleic acid genome Interaction with host cell membranes to form the envelope Delivery of the genome Binding to external receptors of the host cell Transmission of signals that induce uncoating of the genome Induction of fusion with host cell membranes Interaction with internal components of the infected cell to direct transport of the genome to the appropriate site Additional functions Interaction with cellular components for transport to intracellular sites of assembly Interactions with cellular components to ensure an efficient infectious cycle Methods of studying virus structure Electron microscopy Physical methods Chemical methods  Electron microscopy Examine structure and morphology of virus particles Overcomes the shortcomings of light microscopy Types 1. transmission electron microscope (TEM) - valuable 2. scanning electron microscope (SEM) = beautiful Information 1. absolute number of virus particles present in any preparation (total count) 2. appearance and structure of the virions  Astrovirus Rotavirus Adenovirus Calicivirus Physical methods Historical (1930s) filtration through colloidal membranes of various pore sizes - first estimates of the size of virus particles. In the 60s - Sedimentation properties of viruses in ultracentrifuge Differential centrifugation – obtain purified and highly concentrated preparations viruses, free of contamination from host cell components Relative density of particles, measured in solutions of sucrose reveals information about the proportions of nucleic acid and protein Physical methods Spectroscopy Use ultraviolet light to examine the nucleic acid content ofthe particle electrophoretic analysis Study viral proteins or nucleic acids by gel electrophoresis x-ray diffraction Structures of viruses can be determined Resolution of images measured in angstroms (Å) Not suitable for all viruses ✓ Have to propagate virus to a high titre ✓ Have to purify the virus to a high degree ✓ purified virus must also be able to form crystals larg enough to diffract radiation Nuclear magnetic resonance imaging based in the absorption of radiofrequency radiation by atomic nuclei in the presence of an external magnetic field Chemical Methods Classical method Example stepwise disruption of particles by slow alteration of pH or the gradual addition of protein-denaturing agents such as urea, phenol, or detergents. indicate the basis of the stable interactions between its components Can also be used to observe alteration or loss of antigenic sites on the surface of particles Viral capsid All viruses possess a capsid or nucleocapsid (‘core’) Most viral particles appear rod shaped or spherical under EM Small coding capacity of viral genomes Capsid constructed from small number of proteins, regularly and repetitively arranged Maximal contact Non-covalent bonds Results in a symmetrical structure 1. Helical symmetry 2. Icosahedral Symmetry The virus particles can form spontaneously it is in a free energy minimum state Icosahedral Helical Non-enveloped Enveloped Matrix Lipid Glycoprotein Helical symmetry Examples: Influenza, Measles, Rabies All helical animal viruses happen to have ss RNA genomes and an envelope filamentous or rod-like Open structure – can enclose any volume by varying its length The longer helical particles can curve or bend –strength through flexibility Each helix subunit binds identically with each other and on the inside of the helix binds identically with nucleotides of the genome Enveloped with helical nucleocapsid (influenza virus) Icosahedral symmetry Examples: Herpesviruses, adenovirus, picornaviruses Closed structure- restricted volume An icosahedron is a shape consisting of 20 triangular faces arranged around a sphere First noticed by electron microscopy Most icosahedral viruses are made of 60 protein subunits (3 subunits (i.e. a trimer) per face). This is the simplest conformation, and each subunit binds with the neighbours identically. E.g. AV Simple icosahedrons display 2-3-5 rotational symmetry Icosahedral Symmetry Triangulation number (T): Each face of the icosahedron is made of atleast 3 subunits. There are 20 faces. Therefore, larger icosahedral viruses will need to make up the faces with multiples of 60 subunits. Total number of subunits in a structure is 60T Enveloped with icosahedral nucleocapsid (herpesvirus) Quasiequivalence: When a capsid contains >60 subunits, each occupies a more or less equivalent position and forms bonds with their neighbours in a similar fashion. Other capsid architectures Most viruses are helical or icosahedral Examples of exceptions to the rule are retroviruses (HIV) and poxviruses (vaccinia) Retroviridae Two single strands of RNA genome Surrounded by matrix protein Encapsidated by a spherical, cylindrical or conical capsid (e.g. HIV) Poxviridae Large, brick-shaped particles 200 – 400 nm long Extracellular form contains two envelopes > 100 proteins Dumbell shaped core with icosahedral heads with T=7 symmetry. Retrovirus Pox virus Rhabdovirus Filovirus Rhinovirus Parvovirus Influenza Paramyxovirus e.g. RSV, mumps, measles Coronavirus Packaging Nucleic Acid Genome Encapsidation of viral genome is specific process mediated by packaging signals encoded within the viral genome (non-structural proteins) Packaging is mediated by: Direct contact with the viral genome, condensing and protecting the genome OR Packaging by cellular proteins (nucleosomes), Advantages: 1. none of the limited viral genetic information needs to be devoted to DNA-binding proteins 2. viral genome is transcribed by cellular RNAs and enters the infected cell nucleus as nucleoprotein closely resembling cellular templates Envelope Some viruses exit the cell without destroying the host cell envelope They instead ‘bud’ from the surface of the cell, acquiring a lipid envelope in the process. Embedded in the envelope are Transmembrane proteins Contain hydrophobic domains Form a channel through the envelope E.g., ion channels Enables the virus to control the permeability of the membrane E.g. influenza M2 protein External proteins Sits outside the membrane, but anchored with a transmembrane domain Can be associated with each other – multimeric spikes – visible on EM May be glycosylated – glycoproteins Importance Receptor binding Membrane fusion Haemagglutination Major antigens References for this lecture: Alan Cann Principles of Molecular Virology Flint Principles of Virology