Molluscum Contagiosum Virus Transcriptome in Abortively Infected Cultured Cells and a Human Skin Lesion

Abstract

Molluscum contagiosum virus (MOCV), IMPORTANCEThe inability to propagate molluscum contagiosum virus, which causes benign skin lesions in young children and more extensive infections in immunosuppressed adults, has constrained our understanding of the biology of this human-specific virus. In the present study, we characterized the RNAs synthesized in abortively infected cultured cells and a human skin lesion by nextgeneration sequencing. These studies provided an initial transcription map of the MOCV genome, suggested temporal regulation of gene expression, and indicated that the in vitro replication block occurs prior to intermediate and late gene expression. RNA-seq and reporter assays, as described here, may help to further evaluate MOCV gene expression and define conditions that could enable MOCV replication in vitro. M olluscum contagiosum virus (MOCV) is the sole member of the Molluscipoxvirus genus of the Chordopoxvirinae subfamily of the Poxviridae (1). Although many poxviruses cause zoonoses, variola virus (the causative agent of smallpox) and MOCV are the only known human-specific poxviruses (2, 3). MOCV has a worldwide distribution and commonly infects young healthy children, where it causes papular skin lesions that may persist for many months before spontaneous resolution (4). However, widespread disfiguring skin lesions may occur in individuals with immunodeficiencies. For the latter, the most successful therapy is treatment of the underlying immunodeficiency. Although several MOCV variants have been recognized by restriction endonuclease analysis and limited DNA sequencing, they produce indistinguishable lesions (4).Knowledge of MOCV is limited because of the lack of either a cell culture system or useful animal model. The inoculation of primate cells with MOCV produces an abortive infection with cell rounding and related cytopathic effects (CPE) (5). However, the cells regain a more normal appearance after 48 h (6, 7). Evidence that MOCV gene expression is necessary for CPE was supported by the ability of inhibitors of RNA and protein synthesis to prevent this phenomenon (7,8). Following infection, electron microscopy revealed MOCV cores within the cytoplasm, consistent with early gene expression, but the disassembly of the cores or assembly of new virus particles was not observed (7). More direct evidence for early gene expression in human fibroblasts was obtained by RNA-DNA hybridization and reverse transcription-PCR (RT-PCR) (7,

Molluscum contagiosum virus MC80 sabotages MHC-I antigen presentation by targeting tapasin for ER-associated degradation

“…Yet, of the 59 open reading frames (ORFs) which distinguish MCV from orthopoxviruses [8,9], only nine have been well characterized [10,11,12,13,14,15,16,17,18]. Studies regarding the pathogenesis and immune evasion mechanisms employed by MCV have been severely limited by the lack of an animal model or cell line to propagate the virus [19]. Nevertheless, the ORFs unique to MCV likely play a major role in ensuring human-specific epidermal persistence, and should thus be more thoroughly characterized.…”

New Insights into the Evolutionary and Genomic Landscape of Molluscum Contagiosum Virus (MCV) based on Nine MCV1 and Six MCV2 Complete Genome Sequences

“…MCV immune evasion strategies and the involved viral genes have been comprehensively reviewed by Shisler [ 4 ]. A recent study of the MCV1 transcriptome [ 25 ] has consolidated most gene predictions provided by Senkevich et al [ 20 ], and López-Bueno et al [ 26 ] generated the first complete genome sequence of MCV2, suggesting divergent evolutionary pathways of the two main MCV genotypes and indicating the possibility of recombination events.…”

Presence of molluscum contagiosum virus within an epidermal cyst

“…In immunodefi cient patients with AIDS, MCV is a very common opportunistic infection that is still not treatable [ 4 ] . It is not possible to grow MCV in cell culture and no animal model is available [ 5,6 ] . Infection of keratinocytes with MCV leads to a persistent infection for months or years.…”