Virology, Luis Materon, Ph.D.

- UTPA

9/3/12 12:35 PM

Virology, Luis Materon, Ph.D. - UTPA

faculty.utpa.edu

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Virus Evolution

As obligate intracellular parasites with limited genome size, they are among the most efficient and economical of life forms. Encode only those functions that they can not adapt from their hosts. There are obvious differences between the DNA viruses, the retroviruses, and the RNA viruses. It is unclear whether all viruses had a single origin or whether there were multiple origins. DNA viruses do not cause the rapidly moving worldwide pandemics of human disease as RNA viruses (e.g. flu). DNA viruses sequester within their hosts and may be quiescent for decades and then reemerge with their genomes virtually unchanged.

Viruses have evolved ways to:

Increase their coding capacity by utilizing more than one reading frame to encode unrelated proteins. Replicate alternatively in two very different hosts (e.g. the replication of the yellow fever virus in mosquitos and in humans).

Manage Two Competing Structural Requirements:

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Virology, Luis Materon, Ph.D. - UTPA

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Stability to survive outside of a cell for minutes or days. Capability for rapid disassembly upon entry into a susceptible host cell.

Evolution.
For comparative studies, we are in possession of virus isolates not more than 80 years old. From a detailed analysis of the properties of the virus extant today, we can hope to extrapolate Backward toward the origin of viruses Forward toward future patterns of change and evolution, especially among human pathogens. We need to know how viruses change in response to changing environmental factors, how rapidly they change, and to what types of selection pressures they are responding.

Viral Structure
Components: Nucleic acid core and a surrounding protein coat called capsid. In addition, some viruses have a surrounding lipid bilayer membrane called an envelope. A complete virus particle, including its envelope, if it has one, is called a virion.

Nucleic Acids
The British immunologist Peter Medawar (Nobel Prize,1960) once described viruses
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Virology, Luis Materon, Ph.D. - UTPA

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as a piece of bad news wrapped up in protein. ==> genome disrupts host cellular activity and kills cell. Viral genomes consist of DNA or RNA Nucleic Acids Can Be: Single stranded (ss) or double stranded (ds). Linear or circular. Segmented (several fragments). All genetic information in RNA viruses is carried out by RNA. RNA genomes occur only in viruses. The percentage of nucleic acid in relation to protein is about 1% for the influenza virus and about 50% for certain bacteriophages. The total amount of nucleic acid varies from a few thousands nucleotides (or pairs) to as many as 250,000 nucleotides (E. colis chromosome consists of about 4 million np).

The Capsid
Protein shell that protects and determines the shape of the virus. Play key role in attachment of some viruses to host cells.

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Virology, Luis Materon, Ph.D. - UTPA

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Capsids are made of protein units called capsomers. The number, type and arrangement of proteinsmaking the capsomers are characteristic of viruses and are useful in identification and classification. When a virus particle is magnified, the capsid appears as the most prominent geometric feature. Each capsid is made of identical blocks (capsomers), and each capsomer, in turn, is made of a cluster of smaller protein molecules (protomers). Capsomers spontaneously self-assemble into the finished capsid. Depending on how the capsomers are shaped and arranged, the binding results in two different types: Helical capsids (= helical viruses)

Polygonal capsid (= icosahedral viruses) Capsids follow the laws of crystallography. Electron microscopy, X-ray diffraction, biochemical analysis, and immunological techniques have provided much information on structure and composition of viruses.

Morphological Types Icosahedral viruses

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Virology, Luis Materon, Ph.D. - UTPA

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Helical viruses Enveloped viruses Complex viruses

Icosahedral (polygonal) Viruses

Many sided capsids contain two types of capsomers: Triangular hexons that form the flat faces. Round pentons that form the corners. The bonding between capsomers is noncovalent and weaker than the bonding within a capsomer. The hexamers form the edges and faces of the icosahedron, and pentamers are the vertices. A polyhedron with 12 vertices (evenly spaced corners) has 20 equilateral triangles as faces. Capsids of all polygonal viruses have this sort of symmetry but have major variation in capsomer numbers. ==> The capsid of poliovirus has 32 capsomers and adenovirus has 240 capsomers. The pentamers and hexamers may be composed of one type of protein subunit, or the proteins in the pentamers may differ from those of the hexamers.
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Virology, Luis Materon, Ph.D. - UTPA

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Individual capsomers can look either ring or dome shaped, and the capsid itself can appear spherical or cubical. Another factor that alters their appearance is the presence or absence of an outer envelope. There is little organization of nucleic acid in the capsid.

The Icosahedron

It has twofold, threefold, and fivefold axes of rotational symmetry. Symmetry Is the key feature of a structure. It is the collection of all operations (e.g. rotation axes) that bring the object into self-coincidence. Shape Is the overall physical envelope of the object. Many objects that have icosahedral symmetry do not have icosahedral shape; for example, the pentagonal dodecahedron. Inded, most viruses that have icosaheral symmetry do not have icosahedral shape.

Helical viruses
Long thin hollow cylinders composed of distinct protomers (e.g. TMV) The protein subunits are arranged in a helical spiral with the genome fitted into a groove on the inner portion of the protein.

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Virology, Luis Materon, Ph.D. - UTPA

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The nucleic acid is enclosed in the capsid as the protomers are assembled. They are narrow (15-20 nm) and may be quite long (300-400 nm). May be rigid or flexible, depending on the nature of the constituent proteins.

Helical Symmetry of Capsids

Capillovirus Carlavirus Closterovirus (1,000 nm in length) Furovirus Hordeovirus Potevirus Potyvirus Tobamovirus (includes TMV) Tobravirus (100 nm in legth) Why do these plant viruses have evolve this structure? == Not clear. It could be related to the biology of the host plant cell, or alternatively, to the way in which they are transmitted between hosts. Helical, naked (non-enveloped) animal viruses do not exist. A large number of animal viruses have helical symmetry, but all have the addition of an outer lipid envelope (Orthomyxoviridae, Rhabdoviridae, Paramyxoviridae).

Enveloped viruses
Have a typical bilayer membrane outside their capsids.

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Virology, Luis Materon, Ph.D. - UTPA

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Acquire their envelope after they are assembled in the cell as they bud, or move through, one or several membranes. Composition generally is determined by the viral nucleic acid and by the substances derived from the host membranes. Combinations of lipids, proteins and carbohydrates make up most envelopes. Depending on the virus, projections referred to as spikes may or may not extend from the viral envelope.

Spikes
These surface projections are glycoproteins that serve to attach virions to specific receptor sites on susceptible host cell surfaces. In certain viruses (flu), spikes causes various types of RBC to clump or hemagglutinate - a property that is useful in viral identification.

Advantages of the Envelope

Because envelopes are similar to host cell membranes, viruses may be hidden from attack by the host immune system. Envelopes help viruses infect new cells by fusion of the envelope with hosts cell or plasm membrane.

Disadvantages of the Envelope

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Enveloped viruses are damaged easily. Enveloped viruses can be destroyed by increased temperature freezing thawing pH below 6.0 pH above 8.0 lipid solvents disinfectants (chlorine, hydrogen peroxide, phenol) ==> Naked viruses generally are more resistant to such environmental conditions.

Nucleocapsid
Comprises the viral genome together with the capsid. Viruses with only a nucleocapsid and no envelope are called naked (nonenveloped viruses). The Capsid of a Naked Virus Protects the nucleic acid from nuclease enzymes in biological fluids.
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Promotes the viruss attachment to susceptible host cells.

Complex Viruses
Have complex symmetry, but often is assembled from parts synthesized separately (head, tail, capsomer). Have a more intricate structure than the helical, icosahedral, enveloped or naked viruses. Examples The poxviruses are very large viruses that contain a DNA core but lack a regular capsid and have in its place several layers of lipoproteins and coarse surface fibrils. The bacteriophage group. Escherichia coli virus T4 which is composed of a polyhedron head, a tail, whiskers, tail fibers, and other parts.

Other Substances
Enzymes for specific operations within the host cell. Examples are polymerases for synthesizing DNA and RNA, and enzymes for digesting host DNA and proteins. Virus completely lack genes for synthesis of metabolic enzymes. This deficiency has little consequence, because they have adapted to take over
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Virology, Luis Materon, Ph.D. - UTPA

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the hosts metabolic resources. Arenaviruses pack along host ribosomes, and retroviruses borrow the hosts tRNA molecules.

Antibodies and Viral Proteins

When the host has been infected, its immune system produces antibodies (proteins that react with the surface proteins of the virus). Some viruses can escape antibodies because regions of the genes that code for these viruses surface proteins are susceptible to mutations. Mutations produce altered proteins and thus antibodies can not act upon them. That is why we get influenza more than once.

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