Introduction to medicaly important Virues, Summaries of Medical Microbiology

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Introduction to Viruses

The lecture notes

presented are based on

the book "Lippincott's

Illustrated Reviews

Microbiology".

A virus is an infectious agent that is minimally constructed of two components:

1. A genome consisting of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), but not both,
2. a protein-containing structure (capsid) designed to protect the genome. Many viruses have additional structural features, for example, an envelope composed of a protein-containing lipid bilayer, whose presence or absence further distinguishes one virus group from another. A complete virus particle combining these structural elements is called a virion.

In functional terms, a virion can be envisioned as a delivery system that surrounds a nucleic acid payload. The delivery system is designed to protect the genome and enable the virus to bind to host cells. The payload is the viral genome and may also include enzymes required for the initial steps in viral replication—a process that is obligately intracellular. The pathogenicity of a virus depends on a great variety of structural and functional characteristics. Therefore, even within a closely related group of viruses, different species may produce significantly distinct clinical pathologies.

Genome The type of nucleic acid found in the virus particle is perhaps the most fundamental and straightforward of viral properties. It may be RNA or DNA, either of which may be single- stranded (ss) or double stranded (ds). The most common forms of viral genomes found in nature are ss RNA and ds DNA. However, both dsRNA and ssDNA genomes are found in viruses of medical significance.

Single-stranded viral RNA genomes are further subdivided into those of “positive polarity” (that is, of messenger RNA sense, which can therefore be used as a template for protein synthesis), and those of “negative polarity” or are antisense (that is, complementary to messenger RNA sense, which cannot therefore be used directly as a template for protein synthesis). Viruses containing these two types of RNA genomes are commonly referred to as positive-strand and negative-strand RNA viruses, respectively.

Capsid symmetry The protein shell enclosing the genome is, for most virus families, found in either of two geometric configurations helical (rod-shaped or coiled) or icosahedral (spherical or symmetric). The capsid is constructed of multiple copies of a single polypeptide type (found in helical capsids) or a small number of different polypeptides (found in icosahedral capsids), requiring only a limited amount of genetic information to code for these structural components.

1. Helical symmetry: Capsids with helical symmetry, such as the paramyxoviridae, consist of repeated units of a single polypeptide species that—in association with the viral nucleic acid—self-assemble into a helical cylinder. Each polypeptide unit (protomer) is hydrogen- bonded to neighboring protomers. The complex of protomers and nucleic acid is called the nucleocapsid. Because the nucleic acid of a virus is surrounded by the capsid, it is protected from environmental damage.

Among viruses of medical importance, there are both naked and enveloped icosahedral viruses, but all the helical viruses of animals are enveloped and contain RNA. Envelope An important structural feature used in defining a viral family is the presence or absence of a lipid-containing membrane surrounding the nucleocapsid. This membrane is referred to as the envelope. A virus that is not enveloped is referred to as a naked virus. In enveloped viruses, the nucleocapsid is flexible and coiled within the envelope, resulting in most such viruses appearing to be roughly spherical. The envelope is derived from host cell membranes. However, the cellular membrane proteins are replaced by virus-specific proteins, conferring virus-specific antigenicity upon the particle.

VIRAL REPLICATION: THE ONE-STEP GROWTH CURVE

The one-step growth curve is a representation of the overall change, with time, in the amount of infectious virus in a single cell that has been infected by a single virus particle. In practice, this is determined by following events in a large population of infected cells in which the infection is proceeding as nearly synchronously as can be achieved by manipulating the experimental conditions. Whereas the time scale and yield of progeny virus vary greatly among virus families, the basic features of the infectious cycle are similar for all viruses. The one-step growth curve begins with the eclipse period, which is followed by a period of exponential growth.

B. Exponential growth The number of progeny virus produced within the infected cell increases exponentially for a period of time, then reaches a plateau, after which no additional increase in virus yield occurs. The maximum yield per cell is characteristic for each virus-cell system and reflects the balance between the rate at which virus components continue to be synthesized and assembled into virions, and the rate at which the cell loses the synthetic capacity and structural integrity needed to produce new virus particles. This may be from 8 to 72 hours or longer, with yields of 100 to 10,000 virions per cell.

STEPS IN THE REPLICATION CYCLES OF VIRUSES The individual steps in the virus replication cycle are presented as sequentially, beginning with virus attachment to the host cell and leading to penetration and uncoating of the viral genome. Gene expression and replication are followed by assembly and release of viral progeny.

2. Host cell receptor molecules: The receptor molecules on the host cell membrane are specific for each virus family. Not surprisingly, these receptors have been found to be molecular structures that usually carry out normal cell functions. For example, cellular membrane receptors for compounds such as growth factors may also inadvertently serve as receptors for a particular virus. Many of the compounds that serve as virus receptors are present only on specifically differentiated cells or are unique for one animal species. Therefore, the presence or absence of host cell receptors is one important determinant of tissue specificity within a susceptible host species, and also for the susceptibility or resistance of a species to a given virus. Information about the three-dimensional structure of virus binding sites is being used to design antiviral drugs that specifically interact with these sites, blocking viral adsorption.

B. Penetration Penetration is the passage of the virion from the surface of the cell, across the cell membrane and into the cytoplasm. There are two principal mechanisms by which viruses enter animal cells: receptor mediated endocytosis and direct membrane fusion.

1. Receptor-mediated endocytosis: This is basically the same process by which the cell internalizes compounds such as growth regulatory molecules and serum lipoproteins, except the infecting virus particle is bound to the host cell surface receptor in place of the normal ligand. The cell membrane invaginates, enclosing the virion in an endocytotic vesicle (endosome). Release of the virion into the cytoplasm occurs by various routes, depending on the virus but, in general, it is facilitated by one or more viral molecules. In the case of an enveloped virus, its membrane may fuse with the membrane of the endosome, resulting in the release of the nucleocapsid into the cytoplasm.