Molecular and genomic characterization of a novel equine molluscum contagiosum-like virus.

Cases of pox-like lesions in horses and donkeys have been associated with poxviruses belonging to different genera of the family Poxviridae. These include the orthopoxviruses vaccinia virus (VACV), horsepoxvirus (HPXV) and cowpoxvirus (CPXV), as well as a potentially novel parapoxvirus and molluscum contagiosum virus (MOCV). However, with the exception of VACV, HPXV and CPXV, the genomic characterization of the causative agents remains largely elusive with only single short genome fragments available. Here we present the first full-length genome sequence of an equine molluscum contagiosum-like virus (EMCLV) directly determined from skin biopsies of a horse with generalized papular dermatitis. Histopathological analysis of the lesions revealed severe epidermal hyperplasia with numerous eosinophilic inclusion bodies within keratinocytes. Virions were detected in the lesions in embedded tissue by transmission electron microscopy. The genome sequence determined by next- and third-generation sequencing comprises 166 843 nt with inverted terminal repeats (ITRs) of 3473 nt. Overall, 20 of the predicted 159 ORFs have no equivalents in other poxviruses. Intriguingly, two of these ORFs were identified to encode homologues of mammalian proteins involved in immune signalling pathways, namely secreted and transmembrane protein 1 (SECTM1) and insulin growth factor-like family receptor 1 (IGFLR1), that were not described in any virus family so far. Phylogenetic analysis with all relevant representatives of the Poxviridae suggests that EMCLV should be nominated as a new species within the genus Molluscipoxvirus.

Molluscum contagiosum: recent advances in pathogenic mechanisms, and new therapies.

Two poxviruses, Molluscum contagiosum virus (MCV) and Variola virus are specific to humans. MCV is present worldwide and is directly passed by direct skin to skin contact to produce cutaneous and, rarely, mucosal lesions. It occurs predominantly in preadolescent children, sexually active adults, participants in sports with skin to skin contact, and in individuals with impaired cellular immunity. MCV characteristically proliferates within the follicular epithelium, and with routine fixation produces an area of retraction artifact separating layers 1 to 3 of CD34+ stromal cells that immediately surround the follicle from the surrounding dermis. This feature may be obscured when the lesions are inflamed, usually after rupture into the surrounding dermis. MCV is a cytoplasmically replicating virus. MCV-infected cells grow in size, while internal organelles are dislocated and eventually obliterated by a large intracytoplasmic inclusion. Rupture and discharge of the virus-packed cells occurs in a process similar to membrane debris and MCV accumulate in the crater-like ostium; MCV infection is spread by contact with infectious debris. In HIV-1-positive patients the histologic features, as well as the clinical features, may be atypical in patients with MCV infections. Not only are the lesions often large, but they may be verrucous and markedly hyperkeratotic. Recent sequencing of the MCV genome has increased our understanding and investigations into its mechanisms for avoiding host defense mechanisms. These include regions which encode for homologues of cellular chemokines and chemokine-binding proteins, a homolog of MHC1 and a viral FLICE-like inhibitory protein. Treatment, until recently, has depended upon tissue destruction including curettage, cryotherapy, CO(2) laser, electrodesiccation, trichloracetic acid and cantharadin. Recently, topical immune modulators have been used with some success. Understanding of the MCV genome is providing the basis for the development of drugs for therapy and prevention of MCV infections.