ECOLOGICAL BIOCHEMISTRY - Study Guide - V. M. Isaienko 2005

Chapter I. VIRAL INFECTIONS AND ORGANISMAL RESPONSES (General Concepts)

Viruses (from Latin virus meaning poison) represent a non-cellular form of living matter. They are obligate parasites capable of replicating exclusively within the Cells of the organisms they parasitize (host organisms).

Occasionally, when viruses are not clearly classified according to Taxonomy, the broader term "virus-like particles" is widely used.

The distinguishing criterion separating viruses from other organisms is that viruses possess genetic material represented by only a single type of nucleic acid (either DNA or RNA), whereas cellular organisms contain both Types of Nucleic acids. Viruses also differ fundamentally from other organisms in lacking protein-synthesizing machinery. The viral genetic material is replicated solely within the host Organism's Cell, reprogramming the intracellular biochemical processes so that The Cell begins synthesizing viral Proteins. These include both Enzymes essential for viral genome Replication and structural Proteins of the viral capsid, which shields the genetic material from nuclease degradation. In addition to a protein capsid, many viruses possess an outer envelope—the supercapsid—composed of host cell plasma Membrane Lipids and viral Glycoproteins.

In virus-infected cells, new Viral Particles—virions—are assembled from viral Nucleic Acids and Proteins. At the virion stage, prior to entering a cell, a virus exhibits no metabolic activity.

The absolute dependence of viruses on cellular synthesizing systems indicates that viruses are not organisms in the full sense of the word, given that even Mycoplasmas possess their own protein-synthesizing systems.

Since METABOLISM/2.html">THE CONCEPT OF an "individual" cannot be applied to a virion as a specific stage of a viral life cycle, the term "population" is difficult to apply to viruses in a strict sense. However, one can arguably speak of a viral population both at the level of infected organisms and at the level of host organism populations. A viral species is defined as a collection of strains of a given virus that share similarities and thus form species-characteristic traits. A viral strain, much like a bacterial strain, constitutes a pure culture isolated from a specific infected organism and possessing distinct PHYSIOLOGICAL AND BIOCHEMICAL properties.

Based on their Morphology, viruses are classified into rod-shaped (e.g., tobacco mosaic virus), filamentous (potato Y virus), spherical (Influenza virus), cuboidal (smallpox virus), and complex forms (Bacteriophages).

When characterizing The chemical composition of viruses, it should be noted that the mandatory components of a viral particle are one of the two nucleic acids (RNA or DNA), protein, and ash elements. These three components are universal to all viruses, whereas other constituents—such as lipids and CARBOHYDRATES—are far from universally present.

Viruses consisting solely of protein, nucleic acid, and ash elements most commonly belong to the group of simple, so-called minimal viruses, which lack differentiation, intrinsic enzymes, or any specialized structures. Plant viruses and certain animal and insect viruses fall into this category. Conversely, nearly all bacteriophages, despite chemically belonging to minimal viruses, are actually highly complex and differentiated structures. Viruses that, alongside PROTEIN AND NUCLEIC acid, also incorporate lipids and carbohydrates typically belong to complexly organized viruses. The majority of viruses in this group parasitize plants and animals.

Viral DNA molecules can be linear or circular, double-stranded or single-stranded along their entire length, or single-stranded only at the ends. Furthermore, while most nucleotide sequences in the viral genome occur only once, repeated sequences may be present at the termini.

In Introduction/7.html">RNA-containing Viruses, the replicating genetic system consists solely of RNA. The structural integrity of the RNA is essential for its activation. The Molecular Weight of viral RNA varies across a wide range—from 7 • 10⁶ Da in Picornaviruses to over 2 • 10⁸ Da in Retroviruses—although the volume of Genetic information varies to a significantly lesser extent.

The proteins of thus-far investigated viruses consist of standard Amino Acids belonging to the natural L-series. The amino acid ratios in viral proteins closely resemble those found in bacterial, animal, and plant proteins. Dicarboxilic acids predominate in viral protein. This holds true both for viruses with a low nucleic acid content and for those with a high RNA or DNA content.

One of the components occasionally detected in purified viral preparations is carbohydrates, present in amounts exceeding the carbohydrate content of the nucleic acid. Data regarding both the quantitative and qualitative COMPOSITION OF THE carbohydrate component in viruses remain rather contradictory.

They are most abundant in the elementary bodies of influenza virus and classical fowl plague virus—accounting for up to 17%.

The term "viral enzymes" can be used in both a narrow and a broad sense. In the first instance, it refers to enzymatic activity associated with extracellular viral particles. The broad interpretation of the term denotes the entire Complement of enzyme systems involved in viral synthesis within an infected cell—that is, the enzymes of an intracellularly replicating virus.

The presence of enzymes within viral particles has been established with absolute certainty for the Lysozyme and phosphatase activities of bacteriophages and the neuraminidase activity of myxoviruses. In all other cases, either convincing Evidence of the genuinely viral Water/144.html">Origin of the enzymes has not been obtained, or conversely, the enzymatic activity has been conclusively proven to stem from cellular contaminants.

The pathological impact on organisms during viral diseases at the biochemical level involves the interplay of several factors: 1) the Toxic Effect of viral Gene products on the metabolism of infected cells; 2) the host cell's response to viral Gene Expression within infected cells; and 3) the modification of host cell gene expression resulting from structural or functional interaction with the viral genetic material.

In most cases, the symptoms of acute viral diseases can be directly linked to the destruction of cells by the infecting virus.

For a virus to replicate, it must first penetrate a cell. The host range is determined by both the cell types and the organism species that the virus is capable of infecting and supporting replication in. Some viruses have a broad host range, whereas others infect only a single cell type within specific organism species.

Cellular infection by a virus comprises several stages. The first involves the attachment of the virion to the cell surface via a specialized protein—the antireceptor—which binds to a cellular receptor. A classic example of an antireceptor is the influenza virus hemagglutinin. Complex viruses, such as Poxviruses and Herpes simplex virus, may possess multiple types of antireceptor molecules. Moreover, antireceptor molecules can feature multiple domains, each interacting with a specific receptor. Mutations in genes encoding antireceptors sometimes lead to a loss of their ability to interact with receptors.

The Second Stage is the penetration of the viral particle into the cell. This can occur via: 1) translocation of the entire virus across The Plasma Membrane; 2) pinocytosis of viral particles, resulting in their accumulation within cytoplasmic vacuoles; or 3) fusion of the plasma membrane with the viral envelope.

The Third Stage of cellular infection by a virus is the so-called uncoating of the viral particle, which results in the release of the viral genome. Once the viral genome is freed from its protein coat, it serves as an information source for replication and Transcription, acting as a template for The Biosynthesis of corresponding products. The replication of viral genomes proceeds via the duplication of genetic material, namely DNA or RNA. DNA replication is carried out primarily through the same biochemical mechanisms that govern the replication of cellular genetic material. Replication of a viral DNA genome within the host cell is possible if The Genome Functions as a replicon recognized by the replication machinery of either cellular or viral origin. Cellular and viral enzymes may participate jointly in the replication process. In some cases, replication commences only after a series of preliminary stages and the establishment of specific conditions. During a viral infection, the repertoire of cellular enzymes may be supplemented—sometimes by enzymes introduced into the cell by the virion (poxviruses, vesicular stomatitis virus, influenza virus, retroviruses), and sometimes by enzymes synthesized de novo as products of viral genes. The latter are particularly well-documented in certain phages whose reproduction relies on a specialized DNA component. These phages carry the genetic information required to synthesize the corresponding enzymes. Viruses can also induce the synthesis of enzymes that catalyze reactions previously mediated solely by cellular enzymes.

Most RNA-containing viruses replicate by generating RNA copies without the involvement of intermediate DNA templates, allowing their replication to proceed in cells with inhibited DNA Synthesis. These viruses encode their own RNA replicase. Host cells lack such an enzyme. In certain groups of RNA-containing viruses, this nucleic acid is replicated via an intermediate complementary DNA synthesized on the viral RNA template with the aid of Reverse Transcriptase. This enzyme is introduced into the host cell by the virion along with the viral RNA.

During replication, viral nucleic acid is not associated with specific proteins found in mature virions. Under certain conditions, Nucleic Acid Replication takes place even when chemical Protein Synthesis is inhibited. In the process leading to the formation and release of new viral particles, the synthesis of virion proteins typically begins after nucleic acid replication has already commenced. As a result of this protein synthesis, a pool of precursors accumulates, serving as the source of material utilized during capsid assembly. Maturation is a complex and irreversible process: neither the nucleic acid nor the structural proteins incorporated into the complete capsid or a part of it are ever released again within the same cell. Consequently, during capsid assembly, the viral genome is removed from the replicating nucleic acid pool, and capsid proteins are withdrawn from the precursor protein pool. If viruses possess an envelope, it attaches to the capsid at a later stage—either in the Cell Cytoplasm or through interaction with The cell membrane. Such an assembly process, which involves precursor filling stages, explains The phenomenon of phenotypic mixing, whereby a cell coinfected with two distinct yet compatible viruses produces virions with capsids built from subunits encoded by different genomes.

Depending on the duration of the virus's presence in the cell and The Nature of the alterations in its functioning, Three types of viral infection are distinguished. In the first type, newly formed viral particles leave the cell simultaneously, causing it to rupture and die, which leads to a lytic infection. In the second type of viral infection, known as a persistent (stable) infection, new viruses leave the host cell gradually. The cell continues to live and divide while producing new viruses, although its functioning may be altered. The third type of infection is called latent (hidden). The genetic material of the virus integrates into the cell's Chromosomes, and upon Cell Division, it is replicated and passed on to daughter cells. Under certain conditions, in some of the affected cells, the latent virus becomes activated, multiplies, and its progeny leave the cells, leading to either a lytic or persistent type of infection.