Viral coat assemblies

The asymmetric unit contains one copy each of the subunits VPl, VP2, VP3, and VP4. VP4 is buried inside the shell and does not reach the surface. The arrangement of VPl, VP2, and VP3 on the surface of the capsid is shown in Figure 16.12a. These three different polypeptide chains build up the virus shell in a way that is analogous to that of the three different conformations A, C, and B of the same polypeptide chain in tomato bushy stunt virus. The viral coat assembles from 12 compact aggregates, or pen tamers, which contain five of each of the coat proteins. The contours of the outward-facing surfaces of the subunits give to each pentamer the shape of a molecular mountain the VPl subunits, which correspond to the A subunits in T = 3 plant viruses, cluster at the peak of the mountain VP2 and VP3 alternate around the foot and VP4 provides the foundation. The amino termini of the five VP3 subunits of the pentamer intertwine around the fivefold axis in the interior of the virion to form a p stmcture that stabilizes the pentamer and in addition interacts with VP4. 

In the case of HIV, treatment with N-butyl deoxynojirimycin (15) did not prevent viral coat assembly, but it did greatly impair infec-tivity. This is believed to be because of conformation changes in gpl20 coat protein, which prevented its shedding after CE)4 binding, and as a result, prevented gp41 exposure, precluding fusion and entry into the cells (see Sections 2.2.3 and 2.2.6) (203). 

A particle that spontaneously assembles from viral coat proteins in the absence of other viral components. Vims-like particles (VLPs) generated from recombinant coat proteins are used in vaccines against hepatitis B vims and papillomavirus. 

Assembly of llic viral particle. New viral coat proteins assemble mto capsids (the pnitcin envelope that surrounds nucleic acid and associated molecules in the cure) and viral genomes."... 

Interference with assembly of viral coat proteins and viral RNA into new virus particles. Interferons may induce in the ribosomes of the host cells production of enzymes that inhibit translation of viral proteins. Avarol and avarine are thought to interfere with cytoskeletal assembly of virus particles. PROTEASE inhibitors can prevent the release of reverse transcriptase, and HIV-1 proteinase (e.g. saquinavir) are under development or in trial application. 

The outcome of infection by SV40 depends on the organism infected. When simian cells are infected, the virus enters the cell and loses its protein coat. The viral DNA is expressed first as mRNAs and then as proteins. The large-T protein is the first one made (Figure 14.6), triggering the replication of viral DNA, followed by viral coat proteins. The virus takes over the cellular machinery for both replication of DNA and protein synthesis. New virus particles are assembled, and eventually the infected cell bursts, releasing the new virus particles to infect other cells. 

When a virus infects a cell, several events occur that are specific for the invader and hence offer opportunities for selective attack. First of all, there is the contact with the cell, then the penetration of the cell s plasma membrane and the (often simultaneous) rejection of the viral coating-protein. If the virus is of the RN A type, reverse transcriptase is soon in manufacture, but in any case the synthesis of nucleic acid polymerases dominates this early stage of invasion. Next follows the synthesis of viral nucleic acids, structural proteins, and yet more enzymes, followed by the assembly of these components to form the complete virus. Finally, some thousands of these virions are liberated from each cell. Apart from the possibilities for finding selective inhibitors for each of these stages, the patient could also be helped by other drugs to control the secondary (non-viral) symptoms, which are often of an inflammatory or anaphylactic character. 

Filamentous viruses, which are high-aspect ratio agents that proliferate in the presence of host cells, have regular self-assembled structures, and the viral coat proteins on their surface can be genetically or chemically modified to functionalise the nanovector. The tobacco mosaic virus is one of the most extensively studied ID structure for nanoscale applications, and their properties, functionalisation, and assembly into nanodevices are highlighted in the recent review by Ghodssi and co-workers. Mao and co-workers have recently demonstrated that filamentous bacteriophage can be converted into novel photo-responsive nanowires... 

Unlike bacteria, virus particles (virons) are capable of replication only within a host cell. Once within the host cell, the viral nucleic acid directs the synthesis of specific enzymes needed to replicate itself, and directs the synthesis of the viral-coating protein (capsid). The capsid protects the nucleic acid from enzyme attack, and in the absence of high temperatures (above about 70°C the virus may remain intact for several decades. Separation of the nucleic acid from the capsid is necessary in order that the virus becomes active, but the separated components appear to have the capacity for self-assembly to reconstruct the virus particle. 

Most viral coats consist of large numbers of a single kind of protein unit. Some viruses, however, contain more than one kind of protein and may also have an outermost layer of lipid (possibly phos-phorylated) and/or glycoprotein. The well-protected AIDS virus (HIV) is believed to be a complex assembly of this type (Figure 11.52) [135]. The first description of the HIV virus as the causative agent in AIDS was due to Montagnier and Gallo in 1983. 

Intact CCMV or its coat proteins have also been employed as viral building blocks for the self-assembly of molecular materials by Nolte, Comelissen and coworkers. For example, the coat proteins of CCMV were utilized to form DNA-templated tubular assemblies of viral coat proteins. As illustrated in Figure 11, the templates consisted of a single-strand DNA (ssDNA) of repeating thymine units of various lengths (T, where q is the number of thymine bases present). To form the negatively... 

Self-assembly is utilized by nature in a variety of its systems. Such instances are the result of the evolutionary mechanisms that have been shaping the biosphere of our world since the inception of life on Earth. Amongst these natural assembly mechanisms are the self-organization of highly-symmetrical viral coats (1,2,3) and the actions of actin filaments in the cytoplasm of our cells (3,4). 

Viruses represent particularly evolved forms of macro-molecular assemblies. Mature virions are encoded by a protective coat that is formed in part by virally encoded proteins. Viruses come in many shapes and sizes, but they all share the property of using multiple copies of coat proteins to protect their genomic material. In many cases the proteins assemble to form a symmetric shell, where the symmetries are either helical as found in tobacco mosaic virus or icosahedral as seen in the spherical viruses. The use of multiple copies of a protein to form a viral coat is enormously efficient from a genomic point of view however, it introduces several interesting structural problems. 

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