Computer modeling of the aberrant VZV nucleocapsid is relevant to two active areas of herpesviral research: (I) capsid structure and encapsidation of viral DNA and (ii) herpesvirus as immunogens. In the first situation the modeling data complement the elegant studies from the laboratories of Brown, Homa, and Steven. Newcomb et al. (1993) greatly expanded the original studies of HSV icosahedron structure by defining the actual polypeptide components of the pentons and the triplexes. They also showed that treatment with 6.0 M urea quantitatively removed the pentons from the capsid vertices, but the icosahedral structure was preserved. The Homa laboratory cloned the six HSV capsid genes (UL18, UL19, UL26, UL26.5, UL35, and UL38) in baculovirus and expressed the products in insect cells, to form an authentic HSV capsid (Thomsen et al., 1994). They observed that US26.5 gene product (also called VP22a) was necessary to form the inner core of the B capsid. When some of these products were omitted from the insect cell expression system, incomplete capsid shells were formed. Yet the incomplete HSV forms did not resemble the aberrant VZV capsids.

What then is the cause of the aberrant VZV nucleocapsid? Since the percentage of aberrant particles varies with cell type, the VZV genome must contain all required capsid genes. Therefore, we speculate that the difference between the prototypic and the aberrant capsid depends on packaging mechanisms, which in turn may be influenced by the cell substrate. We presume in the prototypic VZV nucleocapsid that an assembly protein is processed and a full-length DNA genome is packaged through a single vertex into the capsid, based on the HSV model (Newcomb and Brown, 1994; Thomsen et al., 1994). We suggest two possible mechanisms to account for the aberrant VZV capsids: a defect in full-length DNA synthesis or an accumulation of the assembly protein. The fact that short segments of viral DNA can enter a capsid has been demonstrated by Vlazny et al. (1982) in the HSV model, but similar studies have not been performed in the various VZV systems. Alternatively, there may be a defect in distribution of the VZV assembly protein, whereby the protein collects in the vertices of the core. For example, earlier studies of CMV capsids from the Gibson Laboratory are compelling. They shoed that CMV capsids with aberrant cores were easily induced when CMV was grown in cell culture in the presence of an inhibitor of DNA synthesis (Lee et al., 1988). Furthermore, the aberrant capsids were enriched for the assembly protein but contained only 1/7 as much DNA as the C capsids Finally , the aberrant CMV capsids were 7% smaller than the other capsids; we also observed that the diameter of the aberrant VZV capsids was slightly less than that of the prototypic VZV capsid.

Grose, C., Harson, R. and Beck, S. (1995). Computer Modeling of Prototypic and Aberrant Nucleocapsids of Varicella-Zoster Virus. Virology 214, 321-329

References:
 

1. Lee, J. Y., Irmiere, A., and Gibson, W. (1988). Primate cytomegalovirus assembly: Evidence that DNA packaging occurs subsequent to B capsid assembly. Virology 167, 87-96
2. Newcomb, W.W., and Brown , J.C. (1994). Induced extrusion of DNA from the capsid of herpes simplex virus type 1. J. Virol. 68, 433-440.
3. Newcomb, W.W., Trus, B.L., Booy, G.P., Steven, A.C., Wall, J.S., and Brown, J.C. (1993). Sturcture of the herpes simplex virus capsid: Molecular composition of the pentons and triplexes. J. Mol.Biol. 232, 499-511.
4. Thomsen, D.R., Roof, L.L., and Homa, F.L. (1994). Assembly of herpes simplex virus (HSV) intermediate capsids in insect cells infected with recombinant baculoviruses expressing HSV capsid proteins. J.Virol. 68, 2442-2457.
5. Vlanzny, D.A., Kwong, A., and Frenkel, N. (1982). Site-specific cleavage/packaging of herpes simplex virus DNA and the selective maturation of nucleocapsids containing full-length viral DNA. Proc. Natl. Acad. Sci. USA 79,1423-1427