General Concepts
Structure and Function
Viruses are small obligate intracellular parasites, which by definition contain either a RNA or DNA genome surrounded by a protective, virus-coded protein coat. Viruses may be viewed as mobile genetic elements, most probably of cellular origin and characterized by a long co-evolution of virus and host. For propagation viruses depend on specialized host cells supplying the complex metabolic and biosynthetic machinery of eukaryotic or prokaryotic cells. A complete virus particle is called a virion. The main function of the virion is to deliver its DNA or RNA genome into the host cell so that the genome can be expressed (transcribed and translated) by the host cell. The viral genome, often with associated basic proteins, is packaged inside a symmetric protein capsid. The nucleic acid-associated protein, called nucleoprotein, together with the genome, forms the nucleocapsid. In enveloped viruses, the nucleocapsid is surrounded by a lipid bilayer derived from the modified host cell membrane and studded with an outer layer of virus envelope glycoproteins.
Classification of Viruses
Morphology: Viruses are grouped on the basis of size and shape, chemical composition and structure of the genome, and mode of replication. Helical morphology is seen in nucleocapsids of many filamentous and pleomorphic viruses. Helical nucleocapsids consist of a helical array of capsid proteins (protomers) wrapped around a helical filament of nucleic acid. Icosahedral morphology is characteristic of the nucleocapsids of many “spherical” viruses. The number and arrangement of the capsomeres (morphologic subunits of the icosahedron) are useful in identification and classification. Many viruses also have an outer envelope.
Chemical Composition and Mode of Replication: The genome of a virus may consist of DNA or RNA, which may be single stranded (ss) or double stranded (ds), linear or circular. The entire genome may occupy either one nucleic acid molecule (monopartite genome) or several nucleic acid segments (multipartite genome). The different types of genome necessitate different replication strategies.
Nomenclature
Aside from physical data, genome structure and mode of replication are criteria applied in the classification and nomenclature of viruses, including the chemical composition and configuration of the nucleic acid, whether the genome is monopartite or multipartite. The genomic RNA strand of single-stranded RNA viruses is called sense (positive sense, plus sense) in orientation if it can serve as mRNA, and antisense (negative sense, minus sense) if a complementary strand synthesized by a viral RNA transcriptase serves as mRNA. Also considered in viral classification is the site of capsid assembly and, in enveloped viruses, the site of envelopment.
Structure and Function
Viruses are inert outside the host cell. Small viruses, e.g., polio and tobacco mosaic virus, can even be crystallized. Viruses are unable to generate energy. As obligate intracellular parasites, during replication, they fully depend on the complicated biochemical machinery of eukaryotic or prokaryotic cells. The main purpose of a virus is to deliver its genome into the host cell to allow its expression (transcription and translation) by the host cell.
A fully assembled infectious virus is called a virion. The simplest virions consist of two basic components: nucleic acid (single- or double-stranded RNA or DNA) and a protein coat, the capsid, which functions as a shell to protect the viral genome from nucleases and which during infection attaches the virion to specific receptors exposed on the prospective host cell. Capsid proteins are coded for by the virus genome. Because of its limited size (Table 41-1) the genome codes for only a few structural proteins (besides non-structural regulatory proteins involved in virus replication). Capsids are formed as single or double protein shells and consist of only one or a few structural protein species. Therefore, multiple protein copies must self assemble to form the continuous three-dimensional capsid structure. Self assembly of virus capsids follows two basic patterns: helical symmetry, in which the protein subunits and the nucleic acid are arranged in a helix, and icosahedral symmetry, in which the protein subunits assemble into a symmetric shell that covers the nucleic acid-containing core.
Table 41-1
Chemical and Morphologic Properties of Animal Virus Families Relevant to Human Disease.
Some virus families have an additional covering, called the envelope, which is usually derived in part from modified host cell membranes. Viral envelopes consist of a lipid bilayer that closely surrounds a shell of virus-encoded membrane-associated proteins. The exterior of the bilayer is studded with virus-coded, glycosylated (trans-) membrane proteins. Therefore, enveloped viruses often exhibit a fringe of glycoprotein spikes or knobs, also called peplomers. In viruses that acquire their envelope by budding through the plasma or another intracellular cell membrane, the lipid composition of the viral envelope closely reflects that of the particular host membrane. The outer capsid and the envelope proteins of viruses are glycosylated and important in determining the host range and antigenic composition of the virion. In addition to virus-specified envelope proteins, budding viruses carry also certain host cell proteins as integral constituents of the viral envelope. Virus envelopes can be considered an additional protective coat. Larger viruses often have a complex architecture consisting of both helical and isometric symmetries confined to different structural components. Small viruses, e.g., hepatitis B virus or the members of the picornavirus or parvovirus family, are orders of magnitude more resistant than are the larger complex viruses, e.g. members of the herpes or retrovirus families:
Classification of Viruses
Viruses are classified on the basis of morphology, chemical composition, and mode of replication. The viruses that infect humans are currently grouped into 21 families, reflecting only a small part of the spectrum of the multitude of different viruses whose host ranges extend from vertebrates to protozoa and from plants and fungi to bacteria.
Morphology
Helical Symmetry
In the replication of viruses with helical symmetry, identical protein subunits (protomers) self-assemble into a helical array surrounding the nucleic acid, which follows a similar spiral path. Such nucleocapsids form rigid, highly elongated rods or flexible filaments; in either case, details of the capsid structure are often discernible by electron microscopy. In addition to classification as flexible or rigid and as naked or enveloped, helical nucleocapsids are characterized by length, width, pitch of the helix, and number of protomers per helical turn. The most extensively studied helical virus is tobacco mosaic virus (Fig. 41-1). Many important structural features of this plant virus have been detected by x-ray diffraction studies. Figure 41-2 shows Sendai virus, an enveloped virus with helical nucleocapsid symmetry, a member of the paramyxovirus family .
Figure 41-1
The helical structure of the rigid tobacco mosaic virus rod.