Capsid,viral assembly

In terms of viral assembly and structure the baculovirus system has been used with tremendous success and some representative examples are discussed in more detail below. Generally speaking, the expressed viral protein (s) can be expected to assemble into particles that are structurally similar if not identical to their native counterparts. This has been shown specifically in the case of the nodavirus Flock House virus, where X-ray analysis of native virions and VLPs showed no differences in the structure of the protein capsid (V. Reddy and J. E. Johnson [The Scripps Research Institute, La JoUa, CA], unpublished data). Similarly, structural investigations at lower resolution, using cryoelectron microscopy and three-dimensional image reconstruction, have confirmed the identity of native and synthetic virions in many other cases. This feature combined with the large amounts that can be obtained has permitted structural analysis of many viruses for which only limited amounts of native virions were available. 

Chemical functionality Rising from their inherent protein capsid-based nature, viral assemblies possess diverse chemical functionalities (i.e., amino acid side chains) that are precisely spaced and can be readily manipulated under mild reaction conditions. This has led to an increasing number of studies directed at further chemical functionalization" and nanomaterials development. 

C. Uetrecht et al.. High-resolution mass spectrometry of viral assemblies molecular composition and stability of dimorphic hepatitis B virus capsids. Proc. Natl. Acad. Sci. USA 105, 9216-9220 (2008)... 

The vims has to mature before it becomes infectious. Maturation usually involves a stmctural change to the vims resulting from the cleavage of a capsid protein. The maturation process may occur during viral assembly or later once the vims has left the host cell. 

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. 

Virus maturation and assembly at the cell membrane or the nuclear membrane has long been seen as a potential target for antiviral compounds. For the virus to mature and be released in a conformation that will insure stability and survival of the viral genome in the exttacellular enviromnent, the protein subunits of the capsid or nucle-ocapsids have to be transported to the assembly point where they will form the final particles around the viral nucleic acid. If this process does not occur in an orderly and programmed manner, the capsid subunits will not form the required multimers and the viral components will become targets for the cellular disposal mechanisms. 

Fig. 1 Antiviral genes inhibit virus replication at different stages of the viral life cycle. Early inhibitors prevent the establishment of the viral genome in the target cell (class I, e.g., entry inhibitors, RT inhibitors for HIV). Intermediate inhibitors prevent viral gene expression or amplification of the viral genome (class II, e.g., siRNAs, antisense RNAs). Late inhibitors prevent virion assembly or release, or inactivate the mature virions (class III, e.g., transdominant core proteins, capsid-targeted virion inactivation, CTVI). A list of antiviral genes in each class is found in Table 1...

The non-enveloped human viruses all have icosahedral capsids. The structural proteins undergo a self-assembly process to form capsids into which the viral nucleic acid is packaged. Most non-enveloped viruses accumulate within the cytoplasm or nucleus and are only released when the cell lyses. 

All enveloped human vimses acquire their phospholipid coating by budding through cellular membranes. The maturation and release of enveloped influenza particles is illustrated in Fig. 3.8. The capsid protein subunits are transported flom the ribosomes to the nucleus, where they combine with new viral RNA molecules and are assembled into the helical capsids. The haemagglutinin and neuraminidase proteins that project fiom the envelope of the normal particles migrate to the cytoplasmic membrane where they displace the normal cell membrane proteins. The assembled nucleocapsids finally pass out from the nucleus, and as they impinge on the altered cytoplasmic membrane they cause it to bulge and bud off completed enveloped particles flxm the cell. Vims particles are released in this way over a period of hours before the cell eventually dies. 

Vainshtein, B. K. (1966). Diffraction of X-Rays by Chain Molecules. Elsevier, Amsterdam. Valery, C., Patemostre, M., Robert, B., Gulik-Krzywicki, T., Narayanan, T., Dedieu, J. C., Keller, G., Torres, M. L., Cherif-Cheikh, R., Calvo, P., and Artzner, F. (2003). Biomimetic organization Octapeptide self-assembly into nanotubes of viral capsid-like dimension. Proc. Natl. Acad. Sci. USA 100, 10258-10262. 

In a paper describing the structure of regular viruses, Caspar and Klug [4] have shown that viral capsids use self-assembly to construct spherical shells up to a hundred nanometers in diameter by utilizing identical copies of proteins as chemical... 

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