BIOCHEMISTRY - L. Stryer - 1984

VOLUME 3

Part IV INFORMATION

CHAPTER 30. VIRUSES

Viruses are infectious Nucleic Acids enclosed in a protective coat. They are the most efficient of all intracellular parasites. Unlike Cells, viruses cannot generate energy through metabolic reactions or synthesize Proteins. They also differ from cells in that they contain either DNA or RNA, but never both simultaneously. Some viruses contain single-stranded nucleic acid, whereas others contain double-stranded. Viruses vary widely in structural complexity, ranging from the Qβ phage—an RNA-containing phage with only 4 genes—to the smallpox virus, whose genome comprises roughly 250 genes. The mature extracellular product of viral reproduction is called a virion (or viral particle). The nucleic acid within the virion is encased in a protein capsid that protects it from enzymatic degradation and mechanical damage. It is the capsid that ensures the delivery of the nucleic acid into the cells of a susceptible host. In some more complex animal viruses, the capsid is surrounded by an envelope containing Lipids and Glycoproteins.

We have already seen that The Study of viruses has had a profound impact on The Development of molecular biology. The discovery of Messenger RNA is a prime example. Researchers' sustained interest in viruses is driven by several factors. First, viral Replication serves as a model for Cell development because it is accompanied by the sequential expression of genes and the assembly of macromolecules into highly ordered structures. The relatively small number of viral genes, the high rate of replication, and the ease of genetic analysis also make viruses highly attractive model systems. Second, viruses provide key insights into Evolutionary Processes and the molecular aspects of host-parasite interactions. Third, certain viruses cause Cancer in experimental animals. The potential role of viruses in human cancers is also being intensively investigated.

30.1 The Coats of Small Viruses Consist of Many Identical Protein Subunits

The total number of Amino Acids in a viral coat always exceeds the number of NUCLEOTIDES in its genome. For instance, the protein coat of a single tobacco mosaic virus (TMV; Fig. 30.2) particle contains about 340,000 amino acid residues, whereas its RNA contains only 6,400 nucleotides. In 1957, Francis Crick and James Watson pointed out that a viral protein coat cannot consist of a single large molecule or a set of many different small proteins, because The amount of viral nucleic acid is far too small to code for such a huge number of amino acid residues. On the other hand, the protein coat cannot be reduced in size, as it must enclose all the nucleic acid. Viruses solve this genetic bottleneck by building their coats from A large number of protein subunits of one or a few types. For example, the TMV coat consists of 2,130 identical subunits (each 158 residues long).

Class="center">Table 30.1. Types of viruses

Fig. 30.1. Electron micrograph of T4 virions in infected cells

Fig. 30.2. Electron micrograph of a tobacco mosaic virus (TMV) particle

The number of ways to construct a viral coat from identical subunits is quite limited. Stability is achieved by maximizing the number of bonds and utilizing identical contacts between subunits. The resulting Structure must be symmetrical. Two Modes of Protein coat Organization are most probable: a cylindrical coat with helical Symmetry, and a spherical coat with icosahedral symmetry (Fig. 30.3). Essentially, all small viruses are either rod-shaped or spherical particles (or a combination of both forms). The rules governing The structure of spherical viruses were formulated by Donald Caspar and Aaron Klug, drawing inspiration from the architectural designs of Buckminster Fuller.

Fig. 30.3. Model of an icosahedron

30.2. Self-Assembly of Tobacco Mosaic Virus (TMV)

The simplest and best-understood viral assembly process is that of TMV. This rod-shaped virus is 3000 Å long, 180 Å in diameter (Fig. 30.4), and has a mass of approximately 40,000 kDa. 2,130 identical coat protein subunits are densely packed in a helix around a single-stranded RNA molecule containing 6,390 nucleotides. The RNA is deeply embedded within the protein, rendering it inaccessible to ribonucleases. Each protein subunit interacts with three nucleotides. When isolated from the protein capsid, the RNA is highly labile, whereas intact TMV retains its infectivity for decades.

Fig. 30.4. Model of a portion of TMV showing the helical arrangement of protein subunits around the single-stranded RNA molecule

The subunits of TMV are not covalently linked to one another. TMV can be dissociated into Protein and RNA using, for example, concentrated acetic acid. In 1955, Heinz Fraenkel-Conrat and Robley Williams demonstrated that, under appropriate conditions, dissociated coat subunits and TMV RNA spontaneously reassociate to form Viral Particles indistinguishable from native TMV in structure and infectivity. This was the first demonstration of the self-assembly of an active biological structure. The self-assembly process is one in which the components spontaneously associate under suitable environmental conditions to form a specific structure.