Host assemblies, viruses

Douglas, T. and Young, M. (1998) Host-guest encapsulation of materials by assembled virus protein cages. Nature, 393, 152-155. 

Viruses are macromolecular assemblies designed to contain and protect the genome, and deliver it to a specific host cell. Viruses come in various sizes, shapes, and forms. Some are large and some small, some are rodlike... 

Once inside the host cell, the vims must replicate its own nucleic acid. To do this, it often uses part of the normal synthesizing machinery of the host cell. If the vims is to continue its growth cycle, viral nucleic acid and viral protein must be propedy transported within the cell, assembled into the infective vims particle, and ultimately released from the cell. All of these fundamental processes involve an intimate utilization of both cellular and viral enzymes. Certain enzymes that are involved in this process are specifically supplied by the invading vims. It is this type of specificity that can provide the best basis for antiviral chemotherapy. Thus an effective antiviral agent should specifically inhibit the viral-encoded or virus-induced enzymes without inhibition of the normal enzymes involved in the biochemical process of the host cell. Virus-associated enzymes have been reviewed (2,3) (Table 1). 

The transcriptional repression can be broken, however, leading to excision of the viral chromosome from the host genome as a circular DNA, followed by replication of viral DNA, followed by activation of genes needed to assemble virus particles. 

Stability Constants Definition and Determination, p. 1360 Viruses as Host Assemblies, p. 1563... 

Self-Assembling Catenanes. p. 1240 Self-Assembly in Biochemistry-, p. 1257 Self-Assembly Terminology, p. 1263 Strict Self-Assembly and Self-Assembly with Covalent Modifications, p. 1372 The Template Effect, p. 1493 Viruses as Host Assemblies, p. 1563... 

FIGURE 1.25 The virus life cycle. Viruses are mobile bits of genetic iuformatiou encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viral-specific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease. 

The basic problem of virus replication can be simply put the virus must somehow induce a living host cell to synthesize all of the essential components needed to make more virus particles. These components must then be assembled into the proper structure and the new virus particles must escape from the cell and infect other cells. The various phases of this replication process in a bacteriophage can be categorized in seven steps ... 

The eclipse is the period during which the stages of virus multiplication occur. This is called the latent period, because no infectious virus particles are evident. Finally, maturation begins as the newly synthesized nucleic acid molecules become assembled inside protein coats. During the maturation phase, the titer of active virus particles inside the cell rises dramatically. At the end of maturation, release of mature virus particles occurs, either as a result of cell lysis or because of some budding or excretion process. The number of virus particles released, called the burst size, will vary with the particular virus and the particular host cell, and can range from a few to a few thousand. The timing of this overall virus replication cycle varies from 20-30 minutes in many bacterial viruses to 8-40 hours in most animal viruses. We now consider each of the steps of the virus multiplication cycle in more detail. 

As seen in the genetic map, the genes after gene 1.1, transcribed by the T7 RNA polymerase, code for proteins that are involved in T7 DNA synthesis, the formation of virus coat proteins, and assembly. Three classes of T7 proteins are formed class I, made 4-8 minutes after infection, which use the cell RNA polymerase class II, made 6-15 minutes after infection, which are made from T7 RNA polymerase and are involved in DNA metabolism class III, made from 6 minutes to lysis, which are transcribed by T7 RNA polymerase and which code for phage assembly and coat protein. This sort of sequential pattern, commonly seen in many large double-stranded DNA phages, results in an efficient channeling of host resources, first toward DNA metabolism and replication, then on to formation of virus particles and release of virus by cell lysis. 

Completely different mechanisms are involved in the self-assembly of the tobacco mosaic virus (TMV). This virus consists of single-strand RNA, which is surrounded by 2,130 identical protein units, each of which consists of 158 amino acid residues. A virus particle, which requires the tobacco plant as a host, has a rodlike structure with helical symmetry ( Stanley needles ). It is 300 nm long, with a diameter of 18nm. The protein and RNA fractions can be separated, and the viral... 

The endoparasite C. sonorensis has evolved with the ability to generate extrachromosomal genetic elements in the form of multiple double-stranded, superhelical DNA molecules. These DNA molecules are amplified in the calyx cell nucleus, packaged into viruses, and secreted in a complex process of viral maturation, which also provides a complex double viral envelope. One viral envelope is assembled in the cell nucleus, and the other is obtained during budding from the calyx cell surface into the oviduct lumen. Viral envelopes, which are derived from cellular membranes, may mediate species-specific virus host cell and tissue interactions. This could be one important aspect of the species-specific endoparasite-host relationship fundamental to parasite survival. 

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