Genus Parapoxvirus

Highly contagious pustular skin infections of sheep, goats and cattle that were unwittingly transmitted to humans from close contact with infected animals, have been the scourge of shepherds, herdsmen and dairy farmers for centuries. In more recent times we recognise that these proliferative pustular lesions are likely to be caused by a group of zoonotic viruses that are classified as parapoxviruses. In addition to infecting the above ungulates, parapoxviruses have more recently been isolated from seals, camels, red deer and reindeer and most have been shown to infect man. The parapoxviruses have one of the smallest genomes of the poxvirus family (140 kb) yet share over 70% of their genes with the most virulent members. Like other poxviruses, the central core of the genomes encode factors for virus transcription and replication, and structural proteins, whereas the terminal regions encode accessory factors that give the parapoxvirus group many of its unique features. Several genes of parapoxviruses are unique to this genus and encode factors that target inflammation, the innate immune responses and the development of acquired immunity. These factors include a homologue of mammalian interleukin (IL)-10, a chemokine binding protein and a granulocyte-macrophage colony stimulating factor /IL-2 binding protein. The ability of this group to reinfect their hosts, even though a cell-mediated memory response is induced during primary infection, may be related to their epitheliotropic niche and the immunomodulators they produce. In this highly localised environment, the secreted immunomodulators only interfere with the local immune response and thus do not compromise the host’s immune system. The discovery of a vascular endothelial growth factor-like gene may explain the highly vascular nature of parapoxvirus lesions. There are many genes of parapoxviruses which do not encode polypeptides with significant matches with protein sequences in public databases, separating this genus from most other mammalian poxviruses. These genes appear to be involved in inhibiting apoptosis, manipulating cell cycle progression and degradation of cellular proteins that may be involved in the stress response, thus allowing the virus to subvert intracellular antiviral mechanisms and enhance the availability of cellular molecules required for replication. Parapoxviruses in common with Molluscum contagiosum virus lack a number of genes that are highly conserved in other poxviruses, including factors for nucleotide metabolism, serine protease inhibitors and kelch-like proteins. It is apparent that parapoxviruses have evolved a unique repertoire of genes that have allowed adaptation to the highly specialised environment of the epidermis.