Virus

What is a Virus?

A virus is an extremely small, infectious agent that is metabolically inert and only replicates in living hosts.

Introduction

A virus is a small parasite that cannot reproduce by itself. Once it infects a susceptible cell, however, a virus can direct the cell machinery to produce more viruses. Most viruses have either RNA or DNA as their genetic material. The nucleic acid may be single or double-stranded. The entire infectious virus particle, called a virion, consists of the nucleic acid and an outer shell of protein. The simplest viruses contain only enough RNA or DNA to encode four proteins. The most complex can encode 100 – 200 proteins.

The study of plant viruses inspired some of the first experiments in molecular biology. In 1935, Wendell Stanley purified and partly crystallized tobacco mosaic virus (TMV); other plant viruses were crystallized soon thereafter. Pure proteins had been crystallized only a short time before Stanley’s work, and it was considered very surprising at the time that a replicating organism could be crystallized.

A wealth of subsequent research with bacterial viruses and animal viruses has provided detailed understanding of viral structure, and virus-infected cells have proved extremely useful as model systems for the study of basic aspects of cell biology. In many cases, DNA viruses utilize cellular enzymes for synthesis of their DNA genomes and mRNAs; all viruses utilize normal cellular ribosomes, tRNAs, and translation factors for synthesis of their proteins. Most viruses common-deer the cellular machinery for macromolecular synthesis during the late phase of infection, directing it to synthesize large amounts of a small number of viral mRNAs and proteins instead of the thousands of normal cellular macromolecules. For instance, animal cells infected by influenza or vesicular stomatitis virus synthesize only one or two types of glycoprotein, which are encoded by viral genes, whereas uninfected cells produce hundreds of glycoprotein. Such virus-infected cells have been used extensively in studies on synthesis of cell-surface glycoprotein. Similarly, much information about the mechanism of DNA replication has come from studies with bacterial cells and animal cells infected with simple DNA viruses, since these viruses depend almost entirely on cellular proteins to replicate their DNA. Viruses also often express proteins that modify host-cell processes so as to maximize viral replication. For example, the roles of certain cellular factors in initiation of protein synthesis were revealed because viral proteins interrupt their action. Finally, when certain genes carried by cancer-causing viruses integrate into chromosomes of a normal animal cell, the normal cell can be converted to a cancer cell.

Since many viruses can infect a large number of different cell types, genetically modified viruses often are used to carry foreign DNA into a cell. This approach provides the basis for a growing list of experimental gene therapy treatments. Because of the extensive use of viruses in cell biology research and their potential as therapeutic agents, we describe the basic aspects of viral structure and function in this section.

A Viral History

Therefore, it's amazing, given the limited technology of the time, that on February 12, 1892, in St. Petersburg, Russia, a scientist by the name of Dmitri Ivanovsky discovered the possibility of a viral organism. Ivanovsky is therefore credited with starting the modern day study of viruses and the diseases caused by them, something we term virology.

It's pretty cool that he was able to even discover the potential for the existence of viruses way before the electron microscope was invented. He did this by noticing that plants were infected by something we now call a virus, after he had ruled out any possibility of a bacterial agent getting through to the plants by using a series of filters designed to stop the bacteria.

It was a Dutch microbiologist, Martinus Beijerinck, who confirmed Ivanovsky's experiments six years later and coined the modern use of the word 'virus' to describe this new agent of disease. However, it wasn't until almost the middle of the 20th century that modern technology finally proved once and for all that the virus was indeed an actual entity, all thanks to the electron microscope.

Viral Structure

After many years of study by many brilliant individuals around the world, we have come to understand some of the basic nature of the viruses that threaten us, plants and even bacteria. For example, the infective form of a virus that exists outside of its host is known as a virion. Since a virion is out there in the environment and not under the protection of its unwitting host, it needs some of its very own protection.

Hence, each virion is composed of an outer protective protein coat called a capsid. This is kind of like the exoskeleton that insects have. This capsid is composed of protein subunits called capsomeres, which are themselves composed of smaller units called protomers. The proteins for the capsid are encoded by the nucleic acids that are housed within the capsid itself. The viral nucleic acid genome can be either DNA or RNA, the organic molecules essential for life.

In some cases, the viral capsid may also be surrounded by a viral envelope, which is a lipid bilayer derived from the host cell and one that increases the infectivity of a virus. This envelope, sometimes called a coat, can change rapidly in response to many different factors and allows the virus to avoid your immune system if necessary.

Viruses do, however, have a few key features in common. These include:

·         A protective protein shell, or capsid

·         A nucleic acid genome made of DNA or RNA, tucked inside of the capsid

·         A layer of membrane called the envelope (some but not all viruses)

Structure and Function

Viruses are small obligate intracellular parasites, which by definition contain either a RNA or DNA genome surrounded by a protective, virus-coded protein coat. Viruses may be viewed as mobile genetic elements, most probably of cellular origin and characterized by a long co-evolution of virus and host. For propagation viruses depend on specialized host cells supplying the complex metabolic and biosynthetic machinery of eukaryotic or prokaryotic cells. A complete virus particle is called a virion. The main function of the virion is to deliver its DNA or RNA genome into the host cell so that the genome can be expressed (transcribed and translated) by the host cell. The viral genome, often with associated basic proteins, is packaged inside a symmetric protein capsid. The nucleic acid-associated protein, called nucleoprotein, together with the genome, forms the nucleocapsid. In enveloped viruses, the nucleocapsid is surrounded by a lipid bilayer derived from the modified host cell membrane and studded with an outer layer of virus envelope glycoproteins.

Classification of Viruses

Morphology: Viruses are grouped on the basis of size and shape, chemical composition and structure of the genome, and mode of replication. Helical morphology is seen in nucleocapsids of many filamentous and pleomorphic viruses. Helical nucleocapsids consist of a helical array of capsid proteins (protomers) wrapped around a helical filament of nucleic acid. Icosahedral morphology is characteristic of the nucleocapsids of many “spherical” viruses. The number and arrangement of the capsomeres (morphologic subunits of the icosahedron) are useful in identification and classification. Many viruses also have an outer envelope.

Chemical Composition and Mode of Replication: The genome of a virus may consist of DNA or RNA, which may be single stranded (ss) or double stranded (ds), linear or circular. The entire genome may occupy either one nucleic acid molecule (monopartite genome) or several nucleic acid segments (multipartite genome). The different types of genome necessitate different replication strategies.

Nomenclature

Aside from physical data, genome structure and mode of replication are criteria applied in the classification and nomenclature of viruses, including the chemical composition and configuration of the nucleic acid, whether the genome is monopartite or multipartite. The genomic RNA strand of single-stranded RNA viruses is called sense (positive sense, plus sense) in orientation if it can serve as mRNA, and antisense (negative sense, minus sense) if a complementary strand synthesized by a viral RNA transcriptase serves as mRNA. Also considered in viral classification is the site of capsid assembly and, in enveloped viruses, the site of envelopment.

Structure and Function

Viruses are inert outside the host cell. Small viruses, e.g., polio and tobacco mosaic virus, can even be crystallized. Viruses are unable to generate energy. As obligate intracellular parasites, during replication, they fully depend on the complicated biochemical machinery of eukaryotic or prokaryotic cells. The main purpose of a virus is to deliver its genome into the host cell to allow its expression (transcription and translation) by the host cell.

A fully assembled infectious virus is called a virion. The simplest virions consist of two basic components: nucleic acid (single- or double-stranded RNA or DNA) and a protein coat, the capsid, which functions as a shell to protect the viral genome from nucleases and which during infection attaches the virion to specific receptors exposed on the prospective host cell. Capsid proteins are coded for by the virus genome. Because of its limited size (Table 41-1) the genome codes for only a few structural proteins (besides non-structural regulatory proteins involved in virus replication). Capsids are formed as single or double protein shells and consist of only one or a few structural protein species. Therefore, multiple protein copies must self assemble to form the continuous three-dimensional capsid structure. Self assembly of virus capsids follows two basic patterns: helical symmetry, in which the protein subunits and the nucleic acid are arranged in a helix, and icosahedral symmetry, in which the protein subunits assemble into a symmetric shell that covers the nucleic acid-containing core.