Vaccinia virus proteolysis—a review

Abstract

It is well known that viruses, as obligate intracellular parasites, must use their hosts' metabolic machinery in order to replicate their genomes and form infectious progeny virions. What is less well known are the details of how viruses make sure that once all the necessary proteins are made, that they assume the correct configuration at the proper time in order to catalyse the efficient assembly of infectious virions. One of the methods employed by viruses to regulate this process is the proteolytic cleavage of viral proteins. Over the past several decades, studies in numerous laboratories have demonstrated that morphogenic proteolysis plays a major and essential role during the assembly and maturation of infectious poxvirus virions. In this review we describe the history of vaccinia virus proteolysis as a prototypic viral system.

Activity, Specificity, and Probe Design for the Smallpox Virus Protease K7L

“…2B). We also found that substitution of Ala at P2 with Gly did not affect the cleavage rate, confirming the proposal that cleavage of natural substrates may be influenced by exosites (12).…”

“…The two variola genes that encode peptidases are H1L and K7L, 4 whereas the same genes in the vaccinia virus are called G1L and I7L, respectively (12). The H1L/G1L gene products are distantly homologous to the M16 family of bacterial and eukaryotic metallopeptidases (6), which either degrade oligopeptides or truncate the signal peptides from mitochondrion/ chloroplast-secreted proteins (13).…”

“…The H1L/G1L gene products are distantly homologous to the M16 family of bacterial and eukaryotic metallopeptidases (6), which either degrade oligopeptides or truncate the signal peptides from mitochondrion/ chloroplast-secreted proteins (13). The function of poxviral metallopeptidase is poorly understood, but it appears to play a complementary role in virus maturation (8,12,14).…”

“…Based on in vivo cleavage data, I7L processes one envelope protein (P21K (A17L)) and four core proteins (P4a (A10L), P4b (A3L), P17K (A12L), and P25K (L4R)) (7,16,18,19) at sites with the AG-X motif (where X is generally a small residue). AG-X motifs occur in other vaccinia proteins as well, but they are not processed, suggesting that additional substrate motifs are required for recognition (12).…”

When good vaccines go wild: Feral Orthopoxvirus in developing countries and beyond

“…During the last decade, several reviews have been written on different aspects of the poxvirus replicative cycle: reproduction [1]; transcription [5,6]; DNA replication [7]; morphogenesis [8]; proteolysis [9]; envelope formation [10]; entry [11]; tropism and immune evasion [12,13]. In this review, we will concentrate on the ability of some orthopoxviruses, including those that are likely to be escaped vaccinia vaccine strains, to persist in nature and re-emerge for no obvious reason.…”