Abstract
A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Surface proteins of enveloped, as well as non-enveloped, viruses become processed by these proteases intracellularly during morphogenesis or extracellularly after egress and during entry in order to produce mature virions activated for infection. Although viruses also take advantage of other proteases, it is when some viruses become reactive with PCs that they may develop high pathogenicity. Besides reacting with furin, some viruses may also react with the PCs of the other specificity group constituted by PC4/PC5/PACE4/PC7. The targeting of PCs for inhibition may result in a useful strategy to treat infections with some highly pathogenic viruses. A wide variety of PC inhibitors have been developed and tested for their antiviral activity in cell-based assays.
Highlights
The regulation of viral cell entry by proteases is a control mechanism common among viruses (Table 1)
human papillomavirus (HPV) particles are constituted by a naked nucleocapsid, and work done with pseudovirion particles has suggested that conformational changes in the nucleocapsid proteins L1 and L2, that are induced upon binding of the virus to cell-surface proteoglycans, prime L2 for cleavage by extracellular or pericellular proprotein convertases (PCs) at the Arg12 residue [24]
The proteolytic processing seems to be HPV-type dependent, as evidenced by the native HPV18 virions being poorly processed during morphogenesis, and their infectivity being mostly dependent on the PCs of the target cells [27]
Summary
The regulation of viral cell entry by proteases is a control mechanism common among viruses (Table 1). Other types of proteases besides PCs can perform the proteolytic maturation of viruses, it has been observed that when PCs process viral proteins, some viruses become comparatively more infective and pathogenic. Kexin-like PCs cleave their substrates at sites specified by a motif composed of P4Arg—P3X—P2X—P1Arg—P10 X, where X is any amino acid residue, and cleavage occurs between the P1Arg and P10 X residues This sequence motif is found in many viral surface proteins and determines cleavage by PCs [3]. The literature on the proteolytic processing of viral surface proteins by PCs and the role that PCs play on the maturation of viruses will be reviewed, and the development of PC inhibitors and their antiviral properties will be discussed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
