Email required. Description required. One Comment Hide Comments Tks!!! Blog Contact Request ebooks Send ebooks Privacy. This fully updated edition represents the rapidly changing field of virology. A major new feature is the inclusion of 26 video interviews with leading scientists who have made significant contributions to the field of virology.
Written in an engagingly readable style and generously illustrated with over full—color illustrations, this approachable volume offers detailed examples that illustrate common principles, specific strategies adopted by different These books teach virology by stressing principles: the rules for reproduction that EVERY virus must follow.
This fully updated edition represents the rapidly changing field of virology. A major new feature is the inclusion of 26 video interviews with leading scientists who have made significant contributions to the field of virology. Home Forum Login. Download PDF Download. Summary of Principles of Virology Page 1. Page 2 About the pagination of this eBook This eBook contains a multi-volume set. This Website Provides Free eBooks to read or download in english fo. Harmful effects of herbicides on the environment pdf invertebrate palaeontology and evolution pdf.
Principles of Virology 2-Volume Set 4th Edition PDF Principles of Virology is the leading virology textbook because it does more than collect and present facts about individual viruses. Share :. Instead, it facilitates an understanding of basic virology by examining the shared processes and capabilities of viruses. Using a set of representative viruses to present the complexity and diversity of a myriad of viruses, this rational approach enables students to understand how reproduction is accomplished by known viruses and provides the tools for future encounters with new or understudied viruses.
This fully updated edition represents the rapidly changing field of virology. 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. Helices are simple structures formed by stacking repeated components with a constant association amplitude and pitch to one another. If this simple relationship is broken, a spiral forms rather than a helix, and a spiral is unsuitable for containing and protecting a virus genome.
Therefore, the pitch of the TMV helix is Flexibility is an important property. Long helical particles are likely to be subject to shear forces and the ability to bend reduces the likelihood of breakage or damage. Helical symmetry is a very useful way of arranging a single protein subunit to form a particle.
Among the simplest helical capsids are those of the bacteriophages of the family Inoviridae, such as M13 and fd. The primary structure of the major coat protein g8p explains many of the properties of these particles.
A mature molecule of g8p consists of approximately 50 amino acid residues a signal sequence of 23 amino acids is cleaved from the precursor protein during its translocation into the outer membrane of the host bacterium and is almost entirely a-helical in structure so that the molecule forms a short rod. Schematic representation of the bacteriophage M13 particle Inoviridae.
Other capsid proteins required for the biological activity of the virion are located at either end of the particle. Inset shows the hydrophobic interactions between the g8p monomers shaded region. A negatively charged region at the amino-terminus that contains acidic amino acids forms the outer, hydrophilic surface of the virus particle, and a basic, positively charged region at the carboxy-terminus lines the inside of the protein cylinder adjacent to the negatively charged DNA genome.
Between these two regions is a hydrophobic region that is responsible for interactions between the g8p subunits that allow the formation of and stabilize the phage particle Figure 2. Inovirus particles are held together by these hydrophobic interactions between the coat protein subunits, demonstrated by the fact that the particles fall apart in the presence of chloroform, even though they do not contain a lipid component.
The value of m protein subunits per complete helix turn is 4. Because the phage DNA is packaged inside the core of the helical particle, the length of the particle is dependent on the length of the genome. In all inovirus preparations, polyphage containing more than one genome length of DNA , miniphage deleted forms containing 0. The structure of the inovirus capsid also explains the events that occur on infection of suitable bacterial host cells.
This interaction causes a conformational change in g8p. Many plant viruses show helical symmetry Appendix 2,. These particles vary from approximately nm Tobravirus to approximately nm Closterovirus in length.
The best studied example is, as stated earlier, TMV from the Tobamovirus group. Quite why so many groups of plant viruses have evolved this structure is not clear, but it may be related either to the biology of the host plant cell or alternatively to the way in which they are transmitted between hosts. Unlike plant viruses, helical, nonenveloped animal viruses do not exist.
A large number of animal viruses are based on helical symmetry, but they all have an outer lipid envelope see later. The reason for this is again probably due to host cell biology and virus transmission mechanisms. All possess single-stranded, negative-sense RNA genomes see Chapter 3.
The molecular design of all of these viruses is similar. The virus nucleic acid and a basic, nucleic-acid-binding protein interact in infected cells to form a helical nucleocapsid. This protein-RNA complex protects the fragile virus genome from physical and chemical damage, but also provides vital functions associated with virus replication. Some of these helical, enveloped animal viruses are relatively simple in structuredfor example, rabies virus and the closely related vesicular stomatitis virus VSV; Figure 2.
These viruses are built up around the negative-sense RNA genome, which in rhabdoviruses is about 11, nucleotides 11 kilo- bases [kb] long. The RNA genome and basic nucleocapsid N protein interact to form a helical structure with a pitch of approximately 5 nm, which, together with two nonstructural proteins, L and NS which form the virus polymerase; see Chapter 4 , makes up the core of the virus particle.
Rhabdovirus particles, such as those of vesicular stomatitis virus, have an inner helical nucleocapsid surrounded by an outer lipid envelope and its associated glycoproteins.
The Function and Formation of Virus Particles 33 in diameter. In common with most enveloped viruses, the nucleocapsid is surrounded by an amorphous layer with no visible structure that interacts with both the core and the overlying lipid envelope, linking them together. This is known as the matrix.
The matrix M protein is usually the most abundant protein in the virus particle; for example, there are approximately copies of the M protein, copies of the N protein, and G protein trimers in VSV particles. The lipid envelope and its associated proteins are discussed in more detail later. Many different groups of viruses have evolved with helical symmetry. Simple viruses with small genomes use this architecture to provide protection for the genome without the need to encode multiple different capsid proteins.
More complex virus particles utilize this structure as the basis of the virus particle but elaborate on it with additional layers of proteins and lipids. The rules for arranging subunits on the surface of a solid are a little more complex than those for building a helix.
In theory, a number of solid shapes can be constructed from repeated subunitsdfor example, a tetrahedron four triangular faces , a cube six square faces , an octahedron eight triangular faces , a dodecahedron 12 pentagonal faces , and an icosahedron, a solid shape consisting of 20 triangular faces arranged around the surface of a sphere Figure 2. Early in the s, direct examination of a number of small spherical viruses by electron microscopy revealed that they appeared to have icosahedral symmetry.
As described earlier, it is more economic in terms of genetics to design a capsid based on a large number of identical, repeated protein subunits rather than fewer, larger subunits. It is unlikely that a simple tetrahedron consisting of four identical protein molecules would be large enough to contain even the smallest virus genome.
If it were, it is probable that the gaps between the subunits would be so large that the particle would be leaky and fail to carry out its primary function of protecting the virus genome. In order to construct a capsid from repeated subunits, a virus must know the rules that dictate how these are arranged. Illustration of the 2e3e5 symmetry of an icosahedron.
Regular icosahedra have faces consisting of equilateral triangles and are formed when the value of P is 1 or 3.
All other values of P give rise to more complex structures with either a left-hand or right-hand skew. This means that 60 identical subunits are required to form a complete capsid 3 subunits per face, 20 faces.
A few simple virus particles are constructed in this way, for example, bacteriophages of the family Microviridae, such as fX An empty precursor particle called the procapsid is formed during assembly of this bacteriophage. Assembly of the procapsid requires the presence of the two scaffolding proteins that are structural components of the procapsid but are not found in the mature virion.
In most cases, analysis reveals that icosahedral virus capsids contain more than 60 subunits, for the reasons of genetic economy just given. A regular icosahedron composed of 60 identical subunits is a very stable structure because all the subunits are equivalently bonded i. With more than 60 subunits it is impossible for them all to be arranged completely symmetrically with exactly equivalent bonds to all their neighbors, since a true regular icosahedron consists of only 20 subunits.
To solve this problem, in Caspar and Klug proposed the idea of quasi-equivalence. Their idea was that subunits in nearly the same local environment form nearly equivalent bonds with their neighbors, permitting self-assembly of icosahedral capsids from multiple subunits. This means that values of T fall into the series 1, 3, 4, 7, 9, 12, 13, 16, 19, 21, 25, 27, 28, and so on. All other values of P give rise to icosahedra of the skew class, where the subtriangles making up the icosahedron are not symmetrically arranged with respect to the edge of each face Figure 2.
With larger more complex viruses there is uncer- taintydthe triangulation number of large and complex Mimivirus particles could have any one of nine values between and Icosahedra with triangulation numbers of 1, 3, and 4. Geminivirus particles consist of twinned icosahedra, fused together at one of the pentameric vertices corners.
This allows some members of this family to contain a bipartite genome see Chapter 3. These direct the assembly of the capsid, typically by bringing together preformed subassemblies of proteins see discussion of fX earlier. Variations on the theme of icosahedral symmetry occur again and again in virus particles.
The capsids of picornaviruses Picornaviridae provide a good illustration of the construction of icosahedral viruses. Detailed atomic structures of the capsids of a number of different picornaviruses have been determined.
These include poliovirus, foot-and-mouth disease virus FMDV , human rhinovirus, and several others. This work has revealed that the structure of these virus particles is remarkably similar to those of many other genetically unrelated viruses, such as insect viruses of the family Nodaviridae and plant viruses from the comovirus group.
The capsid is composed of 60 repeated subassemblies of proteins, each containing three major subunits, VP1, VP2, and VP3. Three virus proteins VP1, 2, and 3 comprise the surface of the particle. A fourth protein, VP4, is not exposed on the surface of the virion but is present in each of the 60 repeated units that make up the capsid. Picornavirus capsids contain four structural proteins. In addition to the three major proteins VP earlier , there is a small fourth protein, VP4.
VP4 is located predominantly on the inside of the capsid and is not exposed at the surface of the particle. The way in which the four capsid proteins are processed from the initial polyprotein see Chapter 5 was discovered by biochemical studies of picornavirus-infected cells Figure 2.
Five VP4 monomers form a hydrophobic micelle, driving the assembly of a pentameric subassembly. The Function and Formation of Virus Particles 39 chemistry, structure, and symmetry of the proteins that make up the picornavirus capsid reveal how the assembly is driven.
Because they are the cause of a number of important human diseases, picorna- viruses have been studied intensively by virologists. This interest has resulted in an outpouring of knowledge about these structurally simple viruses. Detailed knowledge of the structure and surface geometry of rhinoviruses has revealed lots about their interaction with host cells and with the immune system.
In recent years, much has been learned not only about these viruses but also about the identity of their cellular receptors see later and Chapter 4. The information from these experiments has been used to identify a number of discrete antibody-neutralization sites on the surface of the virus particle. Some of these correspond to continuous linear regions of the primary amino acid sequence of the capsid proteins; others, known as conformational sites, result from separated stretches of amino acids coming together in the mature virus.
They correspond primarily to hydrophilic, exposed loops of amino acid sequence, readily accessible to antibody binding and repeated on each of the pentameric subassemblies of the capsid. Enveloped viruses So far, this chapter has concentrated on the structure of naked virus particlesd that is, those in which the capsid proteins are exposed to the external envi- ronment. These viruses escape from infected cells at the end of the replication cycle when the cell dies, breaks down, and lyses, releasing the virions that have been built up internally.
This simple strategy has drawbacks. In some circum- stances, it is wasteful, resulting in the premature death of the cell and reducing the possibilities for persistent or latent infections.
Many viruses have devised strategies to exit their host cell without causing its total destruction. The viability of the cell depends on the integrity of this membrane.
Viruses leaving the cell, therefore, must allow this membrane to remain intact. This is achieved by extrusion budding of the particle through the membrane, during which the particle becomes coated in a lipid envelope derived from the host cell membrane. The virus envelope is therefore similar in composition to the host cell membrane Figure 2.
Enveloped virus particles are formed by budding through a host cell membrane, during which the particle becomes coated with a lipid bilayer derived from the cell membrane. For some viruses, assembly of the structure of the particle and budding occur simultaneously, whereas in others a preformed core pushes out through the membrane.
In the majority of cases, enveloped viruses use cellular membranes as sites allowing them to direct assembly. Formation of the particle inside the cell, maturation, and release are in many cases a continuous process. The site of assembly varies for different viruses. Not all use the cell surface membrane; many use cytoplasmic membranes such as the Golgi apparatus.
Others, such as herpesviruses, which replicate in the nucleus, may utilize the nuclear membrane. In these cases, the virus is usually extruded into some sort of vacuole, in which it is transported to the cell surface and subsequently released. These points are discussed in more detail in Chapter 4. The Function and Formation of Virus Particles 41 If the virus particle became covered in a smooth, unbroken lipid bilayer, this would be its downfall.
Such a coating is effectively inert, and, although effective as a protective layer preventing desiccation of or enzyme damage to the particle, it would not permit recognition of receptor molecules on the host cell. So viruses modify their lipid envelopes with several classes of proteins that are associated in one of three ways with the envelope Figure 2. These can be summarized as follows: n Matrix proteins. These are internal virion proteins whose function is to link the internal nucleocapsid assembly to the envelope.
Some matrix proteins contain transmembrane anchor domains. Others are associated with the membrane by hydrophobic patches on their surface or by proteineprotein interactions with envelope glycoproteins. Several classes of proteins are associated with virus envelopes. Matrix proteins link the envelope to the core of the particle. Virus-encoded glycoproteins inserted into the envelope serve several functions.
External glycoproteins are responsible for receptor recognition and binding, while transmembrane proteins act as transport channels across the envelope. Host-cell-derived proteins are also sometimes found to be asso- ciated with the envelope, usually in small amounts. These proteins are anchored to the envelope and can be subdivided into two further types: n External glycoproteins are anchored in the envelope by a single transmem- brane domain, or alternatively by interacting with a transmembrane protein see next.
Most of the structure of the protein is on the outside of the membrane, sometimes with a short internal tail. Often, individual glycoprotein monomers associate with each other to form the multimeric spikes visible in electron micrographs on the surface of many enveloped viruses.
This enables the virus to control the permeability of the membrane e. Such proteins are often important in modifying the internal environ- ment of the virion, permitting or even driving biochemical changes necessary for maturation of the particle and development of infectivity e. Although there are many enveloped vertebrate viruses, only a few plant viruses have lipid envelopes. Except for plant rhabdoviruses, only a few bunyaviruses that infect plants and members of the Tospovirus genus have outer lipid envelopes.
This limitation does not apply to viruses of prokaryotes, where there are a number of enveloped virus families e. However, there are many viruses whose structure is more complex. Since the last edition of this book was published, the Internet has matured as a medium for sharing information. In the same period, tremendous advances in understanding the structure and function of even the most complex virus particles have been made. It is very difficult to get across the complexity and beauty of some of these structures in a printed book.
It will be very helpful to your understanding to look at the virus structure resources on the web site that accompanies this book. An example of such a group is the Poxviridae. These viruses have oval or brick- shaped particles to nm long. The external surface of the virion is ridged in parallel rows, sometimes arranged helically.
The particles are extremely complex and contain more than different proteins Figure 2. During replication, two forms of particles are produced, extracellular forms that contain two membranes and intracellular particles that have only an inner membrane.
Poxvirus particles are some of the most complex virions known and contain more than virus-encoded proteins, arranged in a variety of internal and external structures. Under the electron microscope, sections of poxvirus particles reveal an outer surface of the virion composed of lipids and proteins.
This layer surrounds the core, which is biconcave dumbbell-shaped , with two lateral bodies whose function is unknown. The core is composed of a tightly compressed nucleo- protein, and the double-stranded DNA genome is wound around it.
Poxviruses are among the most complex particles known. They are at one end of the scale of complexity and are included here as a counterbalance to the descriptions of the simpler viruses given earlier. In between these extremes lie intermediate examples of the tailed bacteriophages.
The order Caudovirales see Chapter 3 , consisting of the families Myoviridae, Siphoviridae, and Podoviridae, has been extensively studied for several reasons. At the end of the tail is a plate that functions in attachment to the bacterial host and also in penetration of the bacterial host cell wall by means of lysozyme-like enzymes associated with the plate.
Inside this compound structure there are also internal proteins and polyamines associated with the genomic DNA in the head, and an internal tube structure inside the outer sheath of the helical tail. The sections of the particle are put together by separate assembly pathways for the head and tail sections inside infected cells, and these come together at a late stage to make up the infectious virion Figure 2.
These viruses illustrate how complex particles can be built up from the simple principles outlined earlier. Each icosahedron has one morphological subunit missing, and the icosahedra are joined at the point such that the mature particle contains protein monomers arranged in 22 morphological subunits. Baculoviruses have attracted interest for a number of reasons. The head and tail sections are assembled separately and are brought together at a relatively late stage. This complex process was painstakingly worked out by the isolation of phage mutants in each of the virus genes involved.
In addition to the major structural proteins, a number of minor scaffolding proteins are involved in guiding the formation of the complex particle. In addition, occluded baculoviruses see later are used as expression vectors to produce large amounts of recombinant proteins. Some baculovirus particles exist in two forms: a relatively simple budded form found within the host insect, and a crystalline, protein-occluded form responsible for environmental persistence.
If this outer protein shell is present, the whole structure is referred to as an occlusion body and the virus is said to be occluded Figure 2. There are two genera of occluded baculoviruses: the Nucleopolyhedrovirus genus, with polyhedral occlusions to 15, nm in diameter and which may contain multiple nucleocapsids within the envelope e.
The function of these large occlusion bodies is to confer resistance to adverse environmental conditions, which enables the virus to persist in soil or on plant materials for extended periods of time while waiting to be ingested by a new host. These viruses can be regarded as being literally armor-plated. Interestingly, the strategy of producing occluded particles appears to have evolved independently in at least three groups of insect viruses.
In addition to the baculoviruses, occluded particles are also produced by insect reoviruses cytoplasmic polyhedrosis viruses and poxviruses entomopoxviruses. To solve this problem, the occlusion body is alkali-labile and dissolves in the high pH of the insect midgut, releasing the nucleocapsid and allowing it to infect the host.
Although the structure of the entire particle has not been completely deter- mined, it is known that the occlusion body is composed of many copies of a single protein of approximately amino acidsdpolyhedrin.
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