Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Cells and Viruses
DNA-containing viruses

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Fig. 4.1.

Viruses are particles containing Nucleic Acids, Proteins, and sometimes Lipids, capable of reproducing exclusively within a host Cell. Outside The Cell, viruses cannot replicate because most of them lack the Enzymes required for the complete synthesis of a mature viral particle. The diameter of Viral Particles (also referred to as virions) ranges from 20 to 300 nm, making them much smaller than even the smallest Prokaryotic Cells. Since the sizes of proteins and certain nucleic acids fall within the 2 to 50 nm range, a viral particle can essentially be considered a macromolecular complex. Due to their minute size and inability to self-replicate, viruses are often classified as non-living entities.

DNA-Containing Viruses carry either single-stranded or double-stranded DNA as their genetic material, which may be either linear or circular. This DNA encodes information for all viral proteins. Viruses are classified based on whether their DNA is single- or double-stranded and whether the host cell is prokaryotic or eukaryotic. Viruses that infect Bacteria are called Bacteriophages.

The basic Structure of a virus consists of a DNA molecule enclosed in a protein coat known as a capsid. However, A wide variety of structural arrangements exists, ranging from a simple protein-coated DNA molecule (e.g., bacteriophage RP) to complex macromolecular complexes surrounded by membrane structures (e.g., the smallpox virus). If a virus possesses a membrane, it is said to be enveloped; if it lacks a membrane, it is termed "non-enveloped" or "naked." Four main classes of capsids are distinguished among DNA-containing viruses: helical, icosahedral, complex non-enveloped, and complex enveloped.

Helical capsids are typically found in filamentous viruses. They are formed through the self-assembly of asymmetric protein subunits (capsomeres) that combine into a tubular structure with helical Symmetry (e.g., in RP). In most cases, the subunits are homogeneous, meaning the virion surface consists of numerous copies of the same protein, although other proteins may reside beneath the outer capsid. The DNA in such viruses is either elongated or tightly coiled in a complex with specialized binding proteins (Chapter 26). Icosahedral capsids are characteristic of most spherical DNA-containing viruses. An icosahedron is a polyhedron with twenty triangular faces, exhibiting cubic symmetry and an approximately spherical shape. The vertices of the triangles converge to form twelve vertices of the icosahedron; pentameric protein structures, or pentons, are typically located at these junction points. These areas may also harbor protein fibers frequently associated with the vertices (e.g., in phiX174—see Fig. 4.1). The faces of the icosahedron are filled with other protein subunits, usually grouped into hexameric structures known as hexons (e.g., in adenovirus—see Fig. 4.1). The number of subunits required to fill the faces is determined by the overall size of the virion; consequently, different icosahedral viruses contain varying numbers of hexons—typically while maintaining a constant number of pentons. The DNA is usually tightly packed within the capsid and is occasionally associated with proteins or Polypeptides that help stabilize its structure.

Complex non-enveloped capsids are typical of bacteriophages: they consist of parts with Different types of symmetry. In bacteriophage T2, for instance, the DNA is located in an icosahedral HEAD, while tubular and fibrillar structures serve to "recognize" the bacterium and inject the DNA into it (Lysozyme, located at the distal end of the tail fiber, also participates in this recognition process).

Complex enveloped capsids occur exclusively in Eukaryotic Cell viruses. They are characteristic of many viruses with a nucleoid consisting of DNA-Protein Complexes. These complexes are surrounded by one or more protein layers possessing either icosahedral or irregular symmetry, and an outer membrane whose protein components are almost entirely of viral origin, whereas its lipid structures are cellular. Infection is the process by which a virus invades a host cell and "reprograms" its metabolic machinery to produce virions. Virus-infected cells either remain alive (in which case the virus is considered non-virulent) or undergo lysis, resulting in the release of viral particles. Lysis is the invariable outcome of infection by DNA-containing bacteriophages. Animal DNA viruses rarely cause lysis; however, cells may die due to chromosomal damage sustained during infection, As a result of the Organism's immunological response, or simply from the disruption of normal cellular Functions by the virus.

Fig. 4.2. GENERALIZED SCHEME OF DNA virus reproduction.

Viral reproduction is a clearly defined cycle that ultimately leads to The formation of mature viral particles following the synthesis of new viral protein molecules and numerous copies of viral DNA. Although the details of this process may vary among different DNA-containing viruses, it is fundamentally universal. In bacterial viruses, the entire cycle can be completed in less than an hour, whereas in many animal viruses, it takes more than a day.

Adsorption of the virus to the host cell is the initial stage of infection. It occurs at specific receptor sites (protein or lipid) on the cell surface, which are recognized by specialized protruding PARTS OF THE virion to which it firmly attaches. In non-enveloped viruses, these structures may be protein spikes (e.g., in adenovirus and bacteriophage T2), whereas in enveloped viruses, they are typically proteins embedded in the viral membrane. During adsorption, specific Protein-Protein Interactions take place, resulting in the initiation of the DNA penetration stage.

The penetration of viral DNA into the host cell varies among different viruses. The DNA of many bacteriophages (e.g., bacteriophage T2) is thought to enter The Cell as follows: the protein sheath contracts like a telescopic structure, and the DNA is "injected" into the bacterium. In animal viruses, the DNA typically enters the cell through a process akin to the fusion of the virion's outer layer with The cell membrane. This is easy to envision for enveloped viruses, where simple membrane fusion occurs; for non-enveloped viruses, the mechanism is less clear. Unlike bacteriophages, the DNA of animal viruses almost always enters the cell accompanied by closely associated proteins; the subsequent dissociation of the DNA from these proteins is carried out by enzymes.

To understand the processes described below, the reader may first need to study Part III of this book.

METABOLISM/31.html">Transcription and Replication of the viral genetic material typically involve host cell enzymes. First, the viral DNA is copied by host cell RNA polymerases to produce mRNA, which is then translated (Chapter 25). DNA copies of the viral genome are also synthesized from certain Viral DNA molecules using either cellular or virus-encoded DNA polymerases (Chapter 20). These DNA copies are subsequently utilized during the assembly of viral particles. In some cases, such as in bacteriophage T4, the earliest newly synthesized viral mRNA molecules are translated into special proteins that modify the host cell polymerases, causing them to cease transcription of cellular genes while retaining The ability to transcribe viral genes. In which part of the cell do transcription and replication of viral DNA take place: The Nucleus or the Cytoplasm? For bacteriophages, this dilemma does not exist; as for animal DNA viruses, neither localization appears to be exclusively used by this group of viruses: in some, transcription and replication occur in the host Cell Nucleus (e.g., herpesvirus), while in others, they take place in the cytoplasm (e.g., Poxviruses).

Translation of viral mRNA on host cell Ribosomes leads to The production of viral proteins. Some of these proteins are subsequently used to build capsids, others bind to viral DNA, likely stabilizing it (in many animal viruses), while still others—though never incorporated into mature virions—participate in their assembly process as enzymes (e.g., in bacteriophage T2).

The assembly of a virus from its components within the host cell can occur spontaneously (in which case it is called self-assembly) or depend on the assistance of accessory proteins. Viral DNA is typically coated with a protein layer—the capsid. The capsid, in turn, may be enclosed within a Membrane Structure usually acquired by the virion from the host cell: upon exiting the cell via budding, the viral particle becomes surrounded by The Plasma Membrane.