Alphaviruses core proteins

One of the most striking results that has emerged from the high-resolution crystallographic studies of these icosahedral viruses is that their coat proteins have the same basic core structure, that of a jelly roll barrel, which was discussed in Chapter 5. This is true of plant, insect, and mammalian viruses. In the case of the picornaviruses, VPl, VP2, and VP3 all have the same jelly roll structure as the subunits of satellite tobacco necrosis virus, tomato bushy stunt virus, and the other T = 3 plant viruses. Not every spherical virus has subunit structures of the jelly roll type. As we will see, the subunits of the RNA bacteriophage, MS2, and those of alphavirus cores have quite different structures, although they do form regular icosahedral shells. 

The core protein of alphavirus has a chymotrypsin-like fold... 

Form-determining roles for viral structural proteins have been suggested for the inner core of blue tongue virus. In this case, 120 P3 subunits pack to form a T=2 icosahedral inner core (Grimes et al, 1998). This core is subsequently tiled by the P7 protein, which is arranged with T=13 symmetry. Thus, the P3 inner core provides a template surface that serves to control P7 polymerization. A similar case has been made for the alphavirus fusion proteins. These viruses, which consist of nucleoprotein... 

Tellinghuisen, T. L., Hamburger, A. E., Fisher, B. R., Ostendorp, R., and Kuhn, R. J. (1999). In vitro assembly of alphavirus cores by using nucleocapsid protein expressed in Escherichia coli. J. Virol. 73, 5309-5319. 

Wengler, G., Boege, U., Wengler, G., Bischoff, H., and Wahn, K. (1982). The core protein of the alphavirus Sindbis virus assembles into core-like nucleoproteins with the viral genome RNA and with other single-stranded nucleic acids in vitro. Virology 118, 401-410. 

Alphaviruses, such as Sindbis virus and Semliki Forest virus, are a group of mosquito-borne, enveloped RNA viruses that can cause encephalitis, fever, arthritis and rashes in mammals. These viruses have two protein shells—an outer glycoprotein layer and an inner core— which are separated by a lipid bilayer, a membrane. Studies by cryoelectron microscopy have shown that... 

Unlike the nucleocapsid core found in the alphaviruses, the flavivirus core is an open structure with no well-defined subunit organization. At the current resolution of flavivirus cryo-EM reconstructions, little can be said about the transmembrane domains that cross the bilayer or the possible contacts the envelope proteins might make with the underlying core (Kuhn et al, 2002). 

Unfortunately, there are no structures available for either the flaviviruses or alphaviruses under conditions approximating the fusion state. For both groups of viruses, entry is believed to occur following attachment of the virus to the cellular receptor and internalization of the particle into an endosome (Kielian, 1995 Heinz and Allison, 2001). Acidification of the endosome results in rearrangement of envelope proteins and subsequent insertion of the fusion peptide into the endosomal membrane (Levy-Mintz and Kielian, 1991 Allison et al., 2001). Ultimately this results in fusion of cellular and viral membranes and release of the nucleocapsid core and genome RNA into the cytoplasm of the infected cell. In vitro experiments... 

The alphaviruses are a group of 26 icosahedral, positive-sense RNA viruses primarily transmitted by mosquitoes [64]. These 700-A-diameter viruses are some of the simplest of the membrane-enveloped viruses, and members of this group cause serious tropical diseases with characteristic symptoms such as myositis, fever, rash, encephalitis, and polyarthritis [65]. The structures of two different alphavirus-Fab complexes have been determined by cryo-TEM Ross River virus (RR) and Sindbis virus (SIN) [66]. The amino acid sequences of the RR and SIN virus structural and nonstructural proteins are 49 and 64% identical, respectively [67]. The viral RNA genome and 240 copies of the capsid protein form the nucleocapsid core [68-73], and the El and E2 glycoproteins form heterodimers that associate as 80 trimeric spikes on the viral surface. Native SIN and RR lack the E3 glycoprotein because it disassociates from the spike complex after its display on the plasma membrane surface [74, 75]. El has a putative fusion domain that may facilitate host membrane penetration [76, 77]. E2 contains most of the neutralizing epitopes and is also probably involved in host cell recognition [78-80]. 

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