Genome Classification and Structure Lecture 2 Genome Classification and Structure

The size of viruses

How are viruses classified? For the first 60 years there was no system Named according to the: associated diseases e,g poliovirus, rabies, type of disease caused e.g murine leukemia virus, sites in the body affected or from which the virus was first isolated e.g rhinovirus, adenovirus. where they were first isolated Sendai virus, Coxsackievirus, after scientists who discovered them e.g Epstein-Barr virus, or for the way people imagined they were contracted e.g dengue = ‘evil spirit’; influenza = ‘influence’ of bad air. Two systems: The Hierarchical Baltimore Classification System

The Hierarchical virus classification system In 1962 Lwoff, R. W. Horne, and P. Tournier advanced a comprehensive scheme for the classification of all viruses consisting of traditional hierarchical phylum - class - order - family - subfamily - genus - species - strain/type. The most imortant principle embodied in this system was that viruses should be grouped according to their shared properties rather than the protperties of the cells or organisms they infect. Four main characteristics are used: Nature of the nucleic acid: RNA or DNA Symmetry of the capsid Presence or absence of an envelope Dimensions of the virion and capsid At the moment classification is really only important from the level of families down. Members within a virus family are ordered with Genomics, the elucidation of evolutionary relationships ba analyses of nucleic acid and protein sequence similarities. In 1962 Lwoff, R. W. Horne, and P. Tournier advanced a comprehensive scheme for the classification of all viruses consisting of phylum - class - order - family - subfamily - genus - species - strain/type. The subsequently formed internat. commitee on the nomenclature of viruses accepted many principles of this system. The most imortant principle embodied in this system was that viruses should be grouped according to their shared properties rather than the protperties of the cells or organisms theyinfect. Four main characteristics are used: Nature of the nucleic acid: RNA or DNA Symmetry of the capsid Presence or absence of an envelope Dimensions of the virion and capsid At the moment classification is really only important from the level of families down. Members within a virus family are ordered with Genomics, the elucidation of evolutionary relationships ba analyses of nucleic acid and protein sequence similarities. All Families have the suffix -viridaee.g. Caliciviridae, Picornaviridae, Reoviridae. Genera have the suffix -virus. Within the Picornaviridae there are 5 genera: enterovirus, cardiovirus, rhinovirus, apthovirus and hepatovirus. The definition of `species' is the most important but difficult assignment to make with viruses. There is an element of subjectivity about it.

Structural Classes Icosahedral symmetry Helical symmetry Non enveloped (“naked”) Enveloped

Icosahedral capsids a) Crystallographic structure of a simple icosahedral virus. b) The axes of symmetry

Helical Symmetry The simplest way to arrange multiple, identical protein subunits is to use rotational symmetry & to arrange the irregularly shaped proteins around the circumference of a circle to form a disc. Multiple discs can then be stacked on top of one another to form a cylinder, with the virus genome coated by the protein shell or contained in the hollow centre of the cylinder. Tobacco mosaic virus (TMV) is representative of one of the two major structural classes seen in viruses of all types, those with helical symmetry.

Helical symmetry TMV, a filamentous virus Closer examination of the TMV particle by X-ray crystallography reveals that the structure of the capsid actually consists of a helix rather than a pile of stacked disks. A helix can be defined mathematically by two parameters: 1.The amplitude (diameter) 2. The pitch (the distance covered by each complete turn of the helix The structure that TMV adopts is self-ordered and corresponds to a free energy minimum. This was and remains a remarkable discovery. TMV, a filamentous virus

Enveloped helical virus Enveloped icosahedral virus

Enveloped Structure of HIV Transmission Electron Micrograph of HIV-1 The nucleocapsid (arrows) can be seen within the envelope. Enveloped Structure of HIV

The Baltimore Classification System Although many viruses are classified into individual families based on a variety of physical and biological criteria, they may also be placed in groups according to the type of genome in the virion. Over 30 years ago virologist David Baltimore devised an alternative classification scheme that takes into account the nature of the viral nucleic acid.

Cont.. One of the most significant advances in virology of the past 30 years has been the understanding of how viral genomes are expressed. Cellular genes are encoded in dsDNA, from which mRNAs are produced to direct the synthesis of protein. Francis Crick conceptualized this flow of information as the central dogma of molecular biology:

The Baltimore classification system Based on genetic contents and replication strategies of viruses. According to the Baltimore classification, viruses are divided into the following seven classes: 1. dsDNA viruses 2. ssDNA viruses 3. dsRNA viruses 4. (+) sense ssRNA viruses (codes directly for protein) 5. (-) sense ssRNA viruses 6. RNA reverse transcribing viruses 7. DNA reverse transcribing viruses where "ds" represents "double strand" and "ss" denotes "single strand".

Virus Classification I - the Baltimore classification All viruses must produce mRNA, or (+) sense RNA A complementary strand of nucleic acid is (–) sense The Baltimore classification has + RNA as its central point Its principles are fundamental to an understanding of virus classification and genome replication, but it is rarely used as a classification system in its own right

Concept By convention, mRNA is defined as a positive (+) strand because it is the template for protein synthesis. A strand of DNA of the equivalent sequence is also called the (+) strand. RNA and DNA strands that are complementary to the (+) strand are, of course, called negative (-) strands. When originally conceived, the Baltimore scheme encompassed six classes of viral genome, as shown in the figure.  Subsequently the gapped DNA genome of hepadnaviruses (e.g. hepatitis B virus) was discovered. The genomes of these viruses comprise the seventh class.  During replication, the gapped DNA genome is filled in to produce perfect duplexes, because host RNA polymerase can only produce mRNA from a fully double-stranded template

From Principles of Virology Flint et al ASM Press

The seven “Baltimore” replication classes

Virus classification This is a based on three principles – that we are classifying the virus itself, not the host the nucleic acid genome the shared physical properties of the infectious agent (e.g capsid symmetry, dimensions, lipid envelope)

How many? In 2010 the International Committee on Taxonomy of Viruses (ICTV) formally recognized: 6 Orders 87 Families 19 Subfamilies 348 Genera and 2285 Species of viruses

Naming Viruses Order has the suffix – virales e.g Picornavirales All Families have the suffix -viridae e.g. Caliciviridae, Picornaviridae, Reoviridae.  Genera have the suffix -virus.  E.g Family Picornaviridae there are 5 genera: enterovirus, cardiovirus, rhinovirus, apthovirus and hepatovirus.

Orders of Viruses Caudovirales (3 Families) Herpesvirales (3 Families) Mononegavirales (4 Families) Nidovirales (3 Families) Picornavirales (5 Families) Tymovirales (4 Families) Virus families not assigned to an order  (65 Families)

Picornavirales Viruses with vertebrate, insects and plant hosts. This group consists of viruses which have (+) sense single stranded RNA genomes. Share a number of common features: conserved RNA-dependent RNA polymerase genome has a protein attached to the 5' end no overlapping open reading frames within the genome all the RNAs are translated into a polyprotein before processing Families within this group: Dicistroviridae (2 Genera) Iflaviridae (1 Genus) Marnaviridae (1 Genus) Picornaviridae (12 Genera) Secoviridae (1 Subfamily and 5 Genera not in a Subfamily)

Picornaviridae Aphthovirus (3 Species) Avihepatovirus (1 Species) Cardiovirus (2 Species) Enterovirus (10 Species) Erbovirus (1 Species) Hepatovirus (1 Species) Kobuvirus (2 Species) Parechovirus (2 Species) Sapelovirus (3 Species) Senecavirus (1 Species) Teschovirus (1 Species) Tremovirus (1 Species)

Enteroviruses Cause a wide range of infections. Poliovirus, the prototypical enterovirus, can cause a subclinical or mild illness, aseptic meningitis, or paralytic poliomyelitis, a disease that has been eradicated in most parts of the world. The nonpolio viruses (group A and B coxsackieviruses, echoviruses, enteroviruses) continue to be responsible for a wide spectrum of diseases in persons of all ages, although infection and illness occur most commonly in infants.

RNA viruses From Principles of Virology Flint et al ASM Press

DNA viruses From Principles of Virology Flint et al ASM Press

Coronavirus (+) RNA genome encodes five translational reading frames. The capped and poly-A subgenomic mRNAs have the same 5’ leader and nested 3’ sequences. NO splicing - “skipping” RNA Pol

Influenza A Multipartite genome of eight helical nucleocapsid segments of (-) strand RNA