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Transcript
The history of viruses dates back to 1670 when the colour breaking of tulips was published in “Trait des tulips”, wherein it was mentioned that the color variegation might be due to a disease. The first scientific proof of the mosaic disease of tobacco came in 1892, when Dimitry Iwanowisky proved that the infected sap was capable of inducing the mosaic disease in healthy plants, even after passing through bacterial- proof filter candles. M W Beinerink1898 gave the name to this infectious agent ‘contagium vivum fluidum’, and latter on as filterable viruses. Meanwhile Bour and Beijerink coined the term virus for this infectious agent. The structural virology started only after the work of Stanely who in 1935 isolated the tobacco mosaic virus in crystalline form for which he was awarded the noble prize. With the advancement of optical instrumentation, structural and molecular virology gained momentum. Characters of viruses Lwoff and Tournier in 1966 described the following characters of viruses: Viruses posses only one type of nucleic acids either DNA or RNA and never both; virions reproduce from their sole nucleic acid; virions are unable to grow or undergo binary fission; they lack the genetic information for the synthesis of Lipmann system; and viruses make use of their host machinery (absolute parasitism). However, F C Bawden reduced the long list of characters, defined viruses as “submicroscopic infective entities that multiply only intracellularly and are potentially pathogenic.” Hahon in 1964 called these definitions as orthodox and treated viruses as transmitters or vehicles of information bearing genetic material and defined viruses as “bits of infectious heredity in search of chromosomes.” This definition seems to be relevant when the second school of thought, i.e. “retrogressive evolution of viruses” is taken into account. General structure of viruses Generally a virus consists of a strand of nucleic acid surrounded by a protein coat; hence viruses are nucleoproteinacious. The whole virus particle is called virion. The protein coat is known as capsid, and the individual protein subunits are called capsomeres. The nucleic acid together with protein coat is called nucleocapsid. Therefore, viruses have three important components which give them the structural organization and help in its replication in an appropriate host cell. These components are: Capsid Genome Envelope and enzymes 1. CAPSID Capsid is a protein covering which encloses the nucleic acid; hence capsid, along with the nucleic acid, is called nucleocapsid. The proteins in the capsid are arranged in smaller identical sub units, each unit is called a capsomere. The arrangement of capsomeres is characteristic for a particular virus. The capsomeres are made up of monomers called protomers. There may be similar or several types of protomers in the capsid.The protomers are connected to one another with the help of bonds. Protomers as well as capsomeres once exposed to proper conditions, associate spontaneously to form the capsid without any external help. This process is called self- assembly. For example in tobacco mosaic virus protomers aggregate to form a two layered disc. It is followed by the association of code proteins with RNA at a special site near 3end of the genome. RNA forms a loop and inserts itself inside the hole of the disc. The association of the protomers continues till the whole of the RNA gets inserted in the capsid. The arrangement of capsomeres in association with the nucleic acid gives a definite symmetry to the virus particle. It may be helical or polyhedral, and some viruses represent the both. The capsid performs the following functions in a virus particle: 1. It protects the nucleic acid from any kind of damage as a result of mechanical force, ultra-violet radiations or due to the activity of host enzymes. 2. It helps the virus in its attachment to a host cell with specific receptors. 3. It enables the virus particle to penetrate the cell membrane of the host to inject the nucleic acid in the host cytoplasm. 2. GENOME Unlike other organisms, viruses show a great variation in their genome. Primarily viruses posses either DNA or RNA as their genetic material, but never both. It may be single- stranded or double- stranded. It can be linear, circular or segmented. The virus genome varies in size from 3500 nucleotides to about 230 kbp (kilo base pairs). With the advancement in the molecular biology techniques, attention has been paid to explore the genomic composition of viruses. The following generalizations may be made about the viral genome: • Plant viruses usually contain RNA. It may be singlestranded (ss RNA) or double- stranded (ds RNA).However, some plant viruses contain DNA. (Table 02) • Animal viruses generally contain double strandedDNA (ds DNA);however, some animal viruses posses single- stranded RNA (ss RNA) and a few have double- stranded RNA (ds RNA) (Tabl 01) • Bacterial virsuses (Bacteriophages) contain DNA (single stranded /double stranded) or RNA (single stranded /double stranded) (Table 03) (01) Adopted (02) Table 01. Animal viruses 02. Plant viruses from Presscort. Table (03) Table 03 Bacterial viruses 2.1 RNA virus genome As mentioned earlier that RNA genome is of two types: Single- stranded RNA and Double- stranded RNA Single stranded RNA (ss RNA) virus genome A single stranded RNA genome may be of plus (+) sense i.e. with the same polarity as that of mRNA, negative (-) sense incapable of gene expression or ambisense, i.e. a mixture of both (+) and (-) sense. Positive (+) sense single stranded RNA The RNA of such viruses after uncoating in the cytoplasm acts as mRNA and directs the synthesis of virus proteins responsible for genome replication. Virus groups with such genomes share some common features, for example: І. Purified (+) sense RNA can induce infection directly without any virus protein. П. Virus genome at its 5’ and 3’ ends posses an untranslated region which do not code for any protein. Ш. Both the ends are modified, 5 end by a methylated nucleotide cap and 3 end by polyadenylation. The modification helps the viral RNA in its recognition by the host cell. The examples of ss + sense RNA viruses are Calciviruses, Astroviruses and viruses,tobamoviruses and bromoviruses. Picorna Negative (-) strand RNA Viruses After uncoating of virus particle in the cytoplasm, the (-) RNA strand remains associated with the transcriptase enzyme to synthesize an mRNA which codes for structural proteins and enzymes that direct the synthesis of + RNA. From + RNA more – RNA strands are synthesised which act as genome for progeny viruses. Rhabdoviruses, Paramyxoviruses and orthomyxoviruses have (-) sense RNA. Rabies virus, tomato spotted wilt virus, and potato yellow dwarf viruses are the common examples. Ambisense genome organisation Some viruses are partly + sense and partly – sense, e.g. Arena viruses and some Buniya viruses. o Double- stranded RNA virus genome In case of animals only Reoviruses posses ds RNA, while as in case of plants Partiviridae and Reoviridae posses ds RNA. Wound Tumor and Rice Dwarf viruses are the common examples. 2.2 DNA virus genomes On the basis of the genome size the DNA genome of viruses can be divided into two groups: (a)Smaller DNA genome, and (b) Larger DNA genome. o Smaller DNA genome The best studied example of the smaller DNA genome is that of bacteriophage M3. The genome of this virus is circular with a single- stranded DNA and has about 7200 nucleotides. The double stranded- DNA genome of smaller size is that of phage lambda with 49 kbp and T4 Phage with a genome size of 160 kbp. The DNA is of linear shape. In case of animal viruses, Parvo virus and Polyoma viruses have smaller DNA genome. However parvo virus is the only single- stranded DNA virus. o Larger DNA genome There is a large number of viruses whose genome is double- stranded and considerably large. The genome of these viruses resembles that of the host cellular genome in many respects, such as presence of histone proteins, polyadenylation, and in presence of split genes through coding and non coding segments. Herpes virus and Adenoviuses are the examples of viruses with large DNA genomes. Herpes virus has a genome size of about 230 kbp with linear double stranded DNA, while as that of Adenovirus is 30-38 kbp in a linear form. Segmented and multipartite genome When the genome is divided in to two or more nucleic acid molecules and is packed in to a single virus particle, the genome is said to be segmented. Orthomyxoviruses, reoviruses and buniya viruses are the examples of segmented virus genomes. Influenza virus has 8 RNA molecules with 890-2341 nucleotides. In case the genome is segmented but packed into separate virus particles, it is said to be multipartite. Such viruses can have two or three capsids and are accordingly called bipartite and tripartite viruses. Multipartite genome is only found in plant viruses, e.g. geminiviruses. In these viruses genome is packed into many capsids. 3. Envelope and enzymes Many viruses, those of plants, animals and bacteria have complex membranous structures around the nucleocapsid, which is called envelope or peplos. The virus envelope glycoproteins consists of a lipid bilayer with embedded in it. Besides, there are carbohydrates. The lipid and carbohydrates are derived from the membranes of the host cell, whereas the glycoproteins are of viral origin. Envelope sometimes give rise projections which are called spikes or peplomers. These structures help the virus in the attachment with the host cell surface. Besides they are used as a taxonomic tool in virus classification. Because of flexible nature of envelope, enveloped viruses have a variable shape and are called pleomorphic. However, in some viruses the envelope is firmly attached to the capsid and the viruses have a constant shape. Based on the presence and absence of envelope, the viruses are grouped as enveloped and non- enveloped viruses. (Tables A & B) DNA animal viruses Non enveloped viruses Parvovirus --- ss DNA Enveloped viruses hepadnavirus --- partially ds DNA Papovirus --- ds DNA Poxvirus--- ds DNA Adenovirus ---ds DNA Herpes virus --- ds DNA Iridovirus---ds DNA Table (A): Enveloped and non- enveloped DNA viruses RNA: animal viruses Non- enveloped viruses Enveloped viruses Picornavirus – ss RNA Rhabdovirus – ss. RNA Reovirus – ds RNA Togavirus---ss RNA Orthomyxovirus ---ss RNA Bunyavirus ---ss RNA Coronavirus ---ss RNA Arenavirus ---ss RNA Retrovirus---ss RNA Paramyxovirus ---ss RNA Table (B): Enveloped and non- enveloped RNA viruses Influenza virus is a well- studied example of an enveloped virus. (Fig.01 A, B). Spikes emerge out 10 nm from the surface at about 7-8 nm intervals. These spikes have enzymatic, absorptive, heamagglutinating and / or antigenic activity. There are two types of spikes present in influenza virus. These are called H.spikes and N. spikes. N. spikes posses an enzyme called neuraminidase (hence the name N. spike), which helps the virus in penetrating the mucous layers of the respiratory epithelium to reach the host cells. Besides neuraminidase helps in assembly process and budding out of virus from the host. Other spikes with hem-agglutinin proteins bind the viruses to red blood cell membranes and cause hemagglutination. Usually viruses lack enzymes, but still some viruses do have enzymes in their capsid or envelo, e.g. Neuraminidase in Influenza virus. Some enzymes are involved in nucleic acid replication, e.g. RNA- dependent RNA polymerase in Influenza virus, and RNA- dependent DNA polymerase in HIV. (a) (b) Fig.01. (a): An electron-micrograph of influenza virus (b): Diagram of Influenza virus (Adopted from Presscort, 2006) Symmetry of Viruses Symmetry refers to any structure, which when rotated around an axis so that the same form is seen from all sides.The morphology of virus is determined by the arrangement of protomers (protein morphological units). Primarily, viruses have two kinds of symmetries, viz. spherical or icosahedral and helical or rod shaped. However, some viruses have binal symmetry, i.e. they are partly helical and partly icosahedral. Therefore, viruses occur in three main shapes viz, icosahedral, helical and complex. o Icosahedral or polyhedral symmetry When protomers aggregate into units of five or six capsomeres, they condense to form an icosahedrons, with 20 faces of equilateral triangles and 20 apices. Pentamers or pentons are at the vertices of the icosahedrons and hexamers or hexons form edges and triangular faces. Viruses with such a type of symmetry are called icosahedral or polyhedral. The number of capsomeres in an icosahedron varies from virus to virus, e.g. ф X 174 has 12 capsomers, turnip yellow mosaic and polio viruses have 32 each, polyoma virus has 72, herpes virus has 162, and adeno viruses have 252 capsomeres. A common example of an icosahedron is the Adeno virus, whose detailed structure is discussed here. (Fig.2 A,B). The Adenoviruses are DNA- containing viruses, which cause mild respiratory infections in humans. Some adenoviruses cause tumors in animals. The virus has a diameter of 75 nm and its coat consists of 11 to 15 distinct proteins. The major coat proteins are called hexons and constitute the major proteins of the faces of the icosahedrons. The hexons are actually trimers, composed of three identical polypeptides. At the five vertices of the icosahedrons are 12 pentons. Some characteristic fibers are attached to the pentons, which help the virus particle in its attachment with the host cell. The moleculer weight of the DNA is 20 × 10⁶ Daltons. (A) (B) Fig.02 (A) A model of an icosa hedral capsid (Adeno Virus) (B) An electron micrograph of Adeno virus. (Adopted from M.T. Madigan) o Helical Symmetry When the protomers are arranged in such a way that they form a long rigid hollow tube, the virus symmetry is said to be helical. Tobacco Mosaic Virus (TMV) is the best studied example of helical capsid (fig. 03 A, B). TMV is an RNA virus about 150 A° thick and 3000 A° long, with a central hole of 40 A°. The capsid is composed of 2130 identical protein subunits, with a molecular weight of 17000 daltons. Each subunit has 158 amino acids. The helix has 16⅓ subunits per turn. There are 130 turns along the helix. The length of the helical viruses is determined by the length of the nucleic acid. The nucleic acid in TMV is a single stranded RNA molecule coiled into a helix and has a diameter of 80 A°. RNA helix has 49 nucleotides with a pitch of 23 A°. There are 6400 nucleotides with a molecular weight of 2× 10⁶ Daltons. (A) (B) Fig03:A. - A model of T.M.V. Helical array of protomers with RNA coiling B. - An electron micrograph of T.M.V at high resolution power (courtesy J.T. Finch) Adopted from Presscort o Complex Symmetry Some viruses do not fit in to the helical or icosahedral symmetries, but rather show a combination of both and, therefore, have a binal symmetry. Pox viruses and bacteriophages are the common examples of complex viruses. The structure of bacteriophage T4 will be discussed here in detail. The bacteriophage is tadpole like, with a polyhedral head and a cylindrical tail. The head is an icosahedron elongated by one or two rows of hexamers in the middle. It has a diameter of 96 X 65 nm, and is made up of 2000 similar protein subunits, and contains a circular double-stranded DNA about 53µm long. The tail has helical symmetry. It is attached with the head by means of a collar or neck piece. It has a central hollow tube, a sheath surrounding the tube and a complex base plate. The sheath is made up of 144 protein subunits arranged in 24 rings and each ring made of six protein subunits. The base plate is hexagonal and has a pin and a jointed tail fiber at each corner. The length of the tail fiber is 130 A°. The tail fibers are the organs of attachment to the specific sites of the host cell (Fig 04 A, B) (A) Fig04:A.—Diagramatic (B) representation bacteriophage. Source: Presscort of T-even B. --- An Electron micrograph of T. even Bacteriophage. Source: Madigan