Polyprotein Proteolytic Processing

Rhinoviri are the causal agents of common colds in humans. Viral replication and maturation is dependent on proteolytic processing of a viral polyprotein by a cysteine protease known as 3C protease. The active-site cysteine in 3C protease... 

AC Palmenberg. Proteolytic procession of picornaviral polyprotein. Annu Rev Microbiol 44 603-623, 1990. 

H Toyoda, MJ Nicklin, MG Murray, CW Anderson, JJ Dunn, FW Studier, E Wim-mer. A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein. Cell 45 761-770, 1986. 

Some proteolytic processing also takes place, especially of polyproteins. A polyprotein is a polypeptide that is cleaved at alternative sites after synthesis to form more than one mature protein. Some hormones are synthesized this way. The mature proteins are then distributed to the plasma membrane, the lysosomes, or the secretory vesicles. 

Proteolytic processing of poliovirus proteins. A single polyprotein is synthesized from the infecting (+)-strand RNA. Subsequent proteolytic processing results in the accumulation of the various poliovirus proteins required for virus production. 

HIV protease is indispensable for the proteolytic processing of viral polyproteins which takes place in the late stage of the viral life cycle (see Figure 3.1). 

A recent report has demonstrated that the proteolytic activity of NS3 plays an additional role in viral infection, beyond polyprotein processing. An important mediator of the cellular immune response is the transcription factor interferon regulatory factor 3 (IRF-3), which becomes activated on infection and then stimulates production of type-1 interferon and other antiviral genes [46]. It was found that expression of heterodimeric NS3/4A... 

Figure 1. Processing of picomavirus. polyprotein by proteolytic enzymes. The numbers in brackets represent molecular weights in thousands. Insert Sodium dodecyl sulfate/ polyacrylamide gel electrophoresis of poliovirus polypeptides, labelled with 5% methionine in infected HeLa cells, a. Infected, labelled at 2.5 hours post infection, b. Labelled in presence of 0.5 niM iodoacetamide. c. Labelled in presence of 0.1 mM tosyl lysine chloromethyl ketone.

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