Viral vectors capsid

P.J. Reier, R.J. Mandel, and N. Muzyczka. 2004. Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential effi-... 

Burger, C., Gorbatyuk, O. S., Velardo, M. J., Peden, C. S., Williams, P., Zolotukhin, S., Reier, P. J., Mandel, R. J. and Muzyczka, N. (2004). Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol. Ther. 10, 302-317. 

Burger C, Gorbatyuk OS, Velardo MJ, Pederr CS, Williams P, Zolotukhirr S, Reier PJ, Marrdel RJ, Muzyczka N (2004) Recombirrarrt AAV viral vectors pseudo typed widr viral capsids from serotypes 1, 2, arrd 5 display differerrdal efficierrcy arrd cell tropism after delivery to differerrt regiorrs of dre cerrtral rrer vous system. Mol Tlrer 10 302-317. 

Davidoff AM, Gray JT, Ng CY, Zhang Y, Zhou J, Spence Y, Bakar Y, Nathwani AC. Comparison of the ability of adeno-associated viral vectors pseudotyped with serotype 2, 5, and 8 capsid proteins to mediate efficient transduction of the liver in murine and nonhuman primate models. Mol Ther 2005 11 875-888. 

Surace E, Auricchio A, Reich S, et al. Delivery of adeno-associated viral vectors to the fetal retina impact of viral capsid proteins on retinal neuronal progenitor transduction. J Virol 2003 77 7957-7963. 

An additional virus that has more recently gained some attention as a possible vector is that of the sindbis virus. A member of the alphavirus family, this ssRNA virus can infect a broad range of both insect and vertebrate cells. The mature virion particles consist of the RNA genome com-plexed with a capsid protein C. This, in turn, is enveloped by a lipid bilayer in which two additional viral proteins (El and E2) are embedded. The E2 polypeptide appears to mediate viral binding to the surface receptors of susceptible cells. The major mammalian cell surface receptor it targets appears to be the highly conserved, widely distributed laminin receptor. 

Contrary to the case of the parvovirus B19, the general rule is normally to obtain a capsid with a monomer ratio similar to the native virus core or capsid. However if it is intended to incorporate a large number of different viral proteins in the capsid or, at least, to express a large number of proteins, it is generally better to use a dual or even an higher-order vector to ensure that the capsids obtained are native-like. 

FIGURE 4.3 Schematic representation comparing the full and deconstructed virus vector strategies, (a) TMV expression vector, (b) Provector system for rapid assembly of viral amplicons in planta. P promoter, TMV Pol TMV polymerase, MP movement protein, GOI gene of interest, CP capsid protein, T terminator, RS recombination site. (Adapted from Gleba et al. (2004). Curr. Opin. Plant Biol., 7, 182-188.)... 

Expression of viral structural proteins in a heterologous system does not always lead to formation of the desired assembly intermediate or end product. This is particularly the case when the proteins are expressed in E. coli or when individual components are expressed separately in different cells. In these cases, the proteins are usually purified and then assembled in vitro. Alternatively, assembly is possible using whole cell lysates. For example, assembly of HSV-1 capsids, which requires a minimum of four structural proteins, was observed on mixing of lysates derived from insect cells infected with different baculovirus vectors (Newcomb et al, 1994). Similarly, reovirus cores, obtained from native virions, could be... 

One of the major concerns in the use of Ad vectors for gene therapy purposes is the induction of an innate immune response. Administration of an Ad vector causes inflammation of the infected tissue, especially in the liver (110, 113-115). The induction of chemokine production at the infected site attracts neutrophils, leading to necrosis and apoptosis in the liver. The development of gutless Ad vectors markedly reduce inflammatory responses and cellular infiltration (116). However, inflammation induced by the viral capsid proteins itself cannot be prevented (110). 

---