Virus Genome structure

Reddy, E.P. Smith, M.J. Srinivasan, A. Nucleotide sequence of Abelson murine leukemia virus genome structural similarity of its transforming gene product to other one gene products with tyrosine-specific kinase activity. Proc. Natl. Acad. Sci. USA, 80, 3623-3627 (1983)... 

Reed, K.E. Rice, C.M. Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties. Cum Top. Microbiol. Immunol. 242, 55-84 (2000). 

Fig. 6. Resolution assessments, (a) Differential phase residual method based on the 45 phase difference criterion used in the 8.5-A resolution (indicated by arrow) structure of the herpesvirus capsid (Zhou et al., 2000). (b) Fourier shell correlation method based on the 0.5 Fourier shell correlation coefficient criterion used in the assessment of effective resolution of the rice dwarf virus (RDV) structure at 6.8 A (Zhou et al, 2001). The imperfect FSC value (<1.0) is partly due to the presence of nonicosahedrally ordered dsRNA genomes within the RDV virions. [Adapted from Zhou et al. (2000, 2001), with permissions from the publishers.]...

F. Genome Structure in Helical Single-Stranded RNA Viruses. 228... 

The satellite ssRNA viruses are a group of ssRNA icosahedral viruses, which are the satellites to certain plant viruses (Pritsch and Mayo, 1989). Satellite tobacco necrosis virus (STNV), a satellite virus to tobacco necrosis virus, was in fact one of the first icosahedral virus structures to be determined by X-ray crystallography (Liljas et al, 1982). In more recent years, two other satellite plant viruses, satellite tobacco mosaic virus (STMV) (Larson et al, 1993, 1998) and satellite panicum mosaic virus (SPMV) (Ban and McPherson, 1995), have been determined. These are perhaps the simplest and smallest icosahedral viruses whose structures have been determined by X-ray crystallography. Of relevance to our discussion is the structure of STMV determined to 1.8-A resolution, which shows extraordinary details about genome organization (Larson et al, 1998 Larson and McPherson, 2001). 

Enveloped viruses have a number of tricks to balance these conflicting constraints. In keeping with the economy of virus genomes and structures, some of these tricks even serve multiple purposes. Eirst, critical functions... 

Genome replication/packaging, in double-stranded RNA viruses, 234 Genome size, 379-380 Genome structural organization... 

HIV-1 PR cleaves the multidomain protein encoded by the virus genome to yield separated structural proteins. Structure-based drug-design studies have shown that in the substrate-cleavage site - two Asp-Thr-Gly loops at the subunit-subunit interface (Fig. 5a) - the almost coplanar conformation of the catalytic Asp dyad is crucial for enzymatic function and for the binding of both substrate and inhibitors [88-90]. 

Hijikata, M., Kato, N., Ootsuyama, Y., Nakagawa, M., and Shimotohno, K. (1991) Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc. Natl. Acad. Sci. USA 88, 5547-5551. 

Fig. 11.4. Genomic structure of transforming viruses in the domestic fowl.

Another icosahedral plant virus used as a viral template is CCMV, a member of the Bromoviridae family. CCMV has a diameter of 28.6 nm and is comprised of a coat protein shell encapsulating a single strand of positive-sense RNA. Similar to CPMV, the genome of CCMV is comprised of multiple strands of RNA, with the three unique strands of RNA packaged individually into virus particles. The individual coat protein capsids of CCMV are composed of 190 amino acid residues and have a total mass of 19.8 kDa. Each coat protein subunit folds into the canonical virus -barrel structure. The protein shell of the virus is composed of 180 identical coat protein subunits. In contrast to CPMV, CCMV particles are stable at pH 5 but swell up to 10% in size when the pH is increased to 7. As illustrated in Figure 7, when the virus is swollen, pores are created within the protein shell, which permit the interior of the virns particles to be penetrated by small molecnles. The transition... 

Eichler and Kruger [147] showed by tissue culture experiments, that various viral antigens related to virus replication and to the synthesis of structural components appear earlier in cells stimulated with . purpurea expressed sap, timunox and TP-1, but not following the stimulation with isoprinosine. Similarly, virus genome containing cells increased after stimulation with thymic preparations (thymostimulin and thymopentin), but not with . purpurea expressed sap and isoprinosine. The authors conclude that the synthesis of proteins or DNA of lym-photropic viruses may be transiently enhanced when lymphoid cells are stimulated by certain non-specific immunostimulants. There was no evidence, however, of increased virus replication. 

Svitkin, Y. V., Ugarova, T. Y., Chernovskaya, T. V., Lyapustin, V. N., Lashkevich, V. A., and Agol, V. I., 1981, Translation of tick-borne encephalitis virus (flavi-virus) genome in vitro Synthesis of two structural polypeptides. Virology 110 26. 

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

A capsid is a proteinaceous shell encasing the viral genome. Viral capsids are polymeric, ordered structures composed of one or more virus encoded subunits. 

The infectious cycle of a (+)-strand RNA virus such as the hepatitis C virus differs by the fate of the viral RNA genome in the infected cell. Upon entry into the cell, the HCV genome is used as a messenger RNA to drive the synthesis of a large polyprotein precursor of about 3,000 residues [2]. The structural proteins are excised from the precursor by host cell signal peptidase. 

---