Abstract
Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following the infection of primary keratinocytes in the epidermis, MCV induces the proliferation of infected cells and this results in the production of wart-like growths. Full productive infection is observed only after the infected cells differentiate. During this prolonged replication cycle the virus must avoid elimination by the host immune system. We therefore sought to investigate the function of the two major histocompatibility complex class-I-related genes encoded by the MCV genes mc033 and mc080. Following insertion into a replication-deficient adenovirus vector, codon-optimized versions of mc033 and mc080 were expressed as endoglycosidase-sensitive glycoproteins that localized primarily in the endoplasmic reticulum. MC080, but not MC033, downregulated cell-surface expression of endogenous classical human leucocyte antigen (HLA) class I and non-classical HLA-E by a transporter associated with antigen processing (TAP)-independent mechanism. MC080 exhibited a capacity to inhibit or activate NK cells in autologous assays in a donor-specific manner. MC080 consistently inhibited antigen-specific T cells being activated by peptide-pulsed targets. We therefore propose that MC080 acts to promote evasion of HLA-I-restricted cytotoxic T cells.
Highlights
Molluscum contagiosum virus (MCV), a member of the genus Molluscipoxvirus, exclusively infects humans and is currently the only endemic human poxvirus [1]
MC033 and MC080 were observed to co-localize with an endoplasmic reticulum (ER)-m arker, but to be relatively distinct from the Golgi apparatus marker, both MCV proteins traffic to the ER when expressed in isolation (Fig. 1)
It is possible that the high GC content of MCV DNA may have caused issues in the mammalian vectors as the issue was overcome when their codon usage was optimized
Summary
Molluscum contagiosum virus (MCV), a member of the genus Molluscipoxvirus, exclusively infects humans and is currently the only endemic human poxvirus [1]. MCV is a dermatotropic poxvirus that infects and induces hyperproliferation of epidermal cells, yet productive infection is realized only following keratinocyte differentiation and culminates in the release of mature virions at the tip of skin papules [2, 3]. While the MCV replication cycle is distinct from that of other characterized poxviruses, the transformation of keratinocytes has parallels with that of the papillomaviruses. Self-limiting MCV infections are primarily observed in children and can persist for months to years. The generally benign nature of skin lesions combined with their remarkable capacity to persist implies that MCV is extremely well adapted to its host. Spontaneous regression follows the induction of an inflammatory response that is characterized by the recruitment of natural killer (NK) cells, T cells and dendritic cells
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