Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 169

Virus particles have been selected during evolution for effective transmission of the nucleic acid genome from one host cell to another within a single organism or among host organisms (Table 4.1). A primary function of an infectious virus particle (called the virion) is protection of the genome, which can be damaged irreversibly by a break in the nucleic acid or by mutation during passage through hostile environments. During its travels, a virus particle may encounter a variety of potentially lethal chemical and physical agents, including proteolytic and nucleolytic enzymes; extremes of pH, humidity, or temperature; and various forms of natural radiation. In all virus particles, the nucleic acid is sequestered within a sturdy barrier formed by extensive interactions among the viral proteins that comprise the protein coat. Such protein-protein interactions can maintain surprisingly stable capsids: many virus particles composed of only protein and nucleic acid survive exposure to large variations in the temperature, pH, or chemical composition of their environment. For example, when dried onto a solid surface, human rotavirus (a major cause of gastroenteritis) loses <20% of its infectivity in 30 days at room temperature, whereas the infectivity of poliovirus (a picornavirus) is reduced by some 5 orders of magnitude within 2 days. This same reduction in infectivity of poliovirus requires >250 days when particles suspended in water are incubated at room temperature at neutral pH. Certain picornaviruses are even resistant to very strong detergents. The highly folded nature of coat proteins and their dense packing to form shells render them largely inaccessible to proteolytic enzymes. Some viruses also possess an envelope, typically derived from cellular membranes, into which viral glycoproteins have been inserted. The envelope adds not only a protective lipid membrane but also an external layer of protein and sugars formed by the glycoproteins. Like the cellular membranes from which they are derived, viral envelopes are impermeable to many molecules and block entry of chemicals or enzymes in aqueous solution.

To protect the nucleic acid genome, virus particles must be stable. However, they must also attach to an appropriate host cell and deliver the genome to the interior of that cell, where the particle is at least partially disassembled. The protective function of virus particles depends on stable intermolecular interactions among their components during assembly, egress from the virus-producing cell, and transmission. On the other hand, these interactions must be reversed readily during entry and uncoating in a new host cell. In only a few cases do we understand the molecular mechanisms by which these apparently paradoxical requirements are met. Nevertheless, it is clear that contact of a virion with the appropriate cell surface receptor or exposure to a specific intracellular environment can trigger substantial conformational changes. Virus particles are therefore metastable assemblies that have not yet attained the minimum free energy conformation (Fig. 4.2). The latter state can be attained only once an unfavorable energy barrier has been surmounted, following induction of the irreversible conformational transitions that are associated with attachment and entry. Virions are not simply inert entities. Rather, they are molecular machines (nanomachines) that play an active role in delivery of the nucleic acid genome to the appropriate host cell and initiation of the reproductive cycle.