Picornavirus

In this chapter we will examine the construction principles of spherical viruses, the structures of individual subunits and the host cell binding properties of the surface of one of the picornaviruses, the common cold virus. 

Figure 16.11 Schematic diagram of a picornavirus particle, illustrating the volume occupied by RNA and protein. The surface of the particle contains protrusions and depressions.

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. 

Picornaviruses construct their shells from 60 copies each of three different polypeptide chains. These 180 subunits are arranged within the shell in a manner very similar to the 180 identical subunits of bushy stunt virus. In some picornaviruses there are protrusions around the fivefold axes, which are surrounded by deep "canyons." In rhinoviruses, the canyons form the virus s attachment site for protein receptors on the surface of the host cells, and they are adjacent to cavities that bind antiviral drugs. 

Arnold, E., et al. Implications of the picornavirus capsid structure for polyprotein processing. Proc. Natl. Acad. ScL USA. 84 21-25, 1987. 

The circumstances under which water becomes contaminated are as varied as the ways water is taken internally. It is then conceivable that almost any virus could be transmitted through the water route. The increased use of water for recreational purposes increases the incidence of human contact with bodies of water and, consequently, with waterborne viruses and bacteria. The major waterborne viruses among pathogens, and the most likely candidates for water transmission, are the picornaviruses (from pico, meaning very small, and RNA, referring to the presence of nucleic acid). The characteristics of picornaviruses are shown in Table 1. Among the picornaviruses are the enteroviruses (polioviruses, coxsackieviruses. 

Table 1. Picornavirus Characteristics (Very Small RNA Viruses)...

Susceptibility of viruses to antimicrobial agents can depend on whether the viruses possess a lipid envelope. Non-lipid viruses are frequently more resistant to disinfectants and it is also likely that such viruses cannot be readily categorized with respect to their sensitivities to antimicrobial agents. These viruses are responsible for many nosocomial infections, e.g. rotaviruses, picornaviruses and adenoviruses (see Chapter 3), and it may be necessary to select an antiseptic or disinfectant to suit specific circumstances. Certain viruses, such as Ebola and Marburg which cause haemorrhagic fevers, are highly infectious and their safe destruction by disinfectants is of paramount importance. 

Diana GD, McKinlay MA, Otto MJ, Akullian V, Oglesby CJ. [[(4,5-Dihy-dro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating. Med Chem 1985 28 1906-1912. 

Diana GD, Oglesby RC, Akullian V, et al. Structure-activity studies of 5-[[4-(4,4-dihydro-2-oxazolyl)phenoxy]alkyl]-3-methylisoxazoles inhibitors of picornavirus uncoating. J Med Chem 1987 30 383-388. 

Diana GD, Cutcliffe D, Oglesby RC, Otto MJ, Mallamo JP, Akullian V, McKinlay MA. Synthesis and structure-activity studies of some disubsti-tuted phenylisoxazoles against human picornavirus. J Med Chem 1989 32 450-455. 

Diana GD, Rudewicz P, Pevear DC, et al. Picornavirus inhibitors trifluo-romethyl substitution provides a global protective effect against hepatic metabolism. J Med Chem 1995 38 1355-1371. 

Semler BL, Wimmer E (2002) Molecular biology of picornaviruses. ASM, Washington DC... 

Picornain 2A [EC 3.4.22.29] catalyzes the hydrolysis of peptide bonds including the selective cleavage of a particular peptide bond in the picornavirus polyprotein. Picornain 3C [EC 3.4.22.28] catalyzes the selective hydrolysis of the Gin—Gly bond in the poliovirus polyprotein. 

Figure 16.2 A plot of peak signal-to-noise versus maximum vector length for the / = 72 section of a self-rotation function for a picornavirus (approx. 150 A radius), space group P22i2i, a = 354,...

Most vaccine vectors developed to date are viral-based, with poxviruses, picornaviruses and adenoviruses being used most. In general, such recombinant viral vectors elicit both strong humoral and cell-mediated immunity. The immunological response (particularly the cell-mediated response) to subunit vaccines is often less pronounced. 

Three regions of the picornavirus stmcture deserve special attention because they appear to play crucial roles in the viral life cycle as well as bear on the function of the capsid-binding compounds. These regions are the canyon, the VP1 hydrophobic pocket, and the [3 cylinder. 

Some compounds which have been shown to inhibit picornavirus replication. These are thought to bind in the VP1 hydrophobic pocket. References are indicated on the figure. 

Many of the picornavirus structures have been shown to have electron density in their VP1 pockets even in the absence of any added drug. These densities have been modeled as fatty acids or similar compounds [12,15,56,70-72]. The occurrence of these pocket factors have led some to hypothesize that these factors perform a similar function as do capsid-binding inhibitors, that is, to stabilize the virions [15,24,41,73,74]. 

The structures of the picornaviruses (native, with receptor bound, in the presence of acid, with a myriad of compounds bound, and of acid- and drug-resistant mutants) have yielded valuable information about possible molecular mechanisms for their uncoating. These same studies have suggested the mechanism by which these uncoating inhibitors work. A by-product of this research is the hypothesis that these compounds may mimic naturally occurring factors that occupy the VP1 pocket. The hunt for these natural compounds and their significance is underway. 

Rozhon E, Cox S, Buontempo P, et al. SCH-38057—a picornavirus capsid-binding molecule with antiviral activity after the initial stage of viral uncoating. Antivir Res 1993 21(1) 15—35. 

The two groups of viruses, RNA and DNA, are further divided according to size, morphology, and biological and chemical properties. Thus, the icosahedral RNA viruses that are ether stable are divided into the picornaviruses and the reoviruses. The name picornavirus comes from pico... 

AG Porter. Picornavirus nonstructural proteins emerging roles in virus replication and inhibition of host cell functions. J Virol 67 6917-6921, 1993. 

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