Review
Molluscum contagiosum virus infection

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Summary

Molluscum contagiosum virus is an important human skin pathogen: it can cause disfigurement and suffering in children, in adults it is less common and often sexually transmitted. Extensive and persistent skin infection with the virus can indicate underlying immunodeficiency. Traditional ablative therapies have not been compared directly with newer immune-modulating and specific antiviral therapies. Advances in research raise the prospect of new approaches to treatment informed by the biology of the virus; in human skin, the infection is localised in the epidermal layers, where it induces a typical, complex hyperproliferative lesion with an abundance of virus particles but a conspicuous absence of immune effectors. Functional studies of the viral genome have revealed effects on cellular pathways involved in the cell cycle, innate immunity, inflammation, and cell death. Extensive lesions caused by molluscum contagiosum can occur in patients with DOCK8 deficiency—a genetic disorder affecting migration of dendritic and specialised T cells in skin. Sudden disappearance of lesions is the consequence of a vigorous immune response in healthy people. Further study of the unique features of infection with molluscum contagiosum virus could give fundamental insight into the nature of skin immunity.

Introduction

Viral skin infections are frequently seen in both primary care and dermatology practices worldwide. The infections are most commonly caused by herpesviruses, papillomaviruses, and molluscum contagiosum virus. Since the eradication of smallpox, molluscum contagiosum has been the principal poxvirus cause of human disease.1, 2, 3

Recognised nearly 200 years ago, molluscum contagiosum warrants clinical and basic research because it causes a substantial health-care burden and adversely affects quality of life. The virus is uniquely adapted to human skin, both in terms of growth and evasion of local immune defences. Molluscum contagiosum is distinct from other poxviruses because of its host and tissue adaptations. It infects only the skin and, rarely, the mucous membranes.4 The virus has developed efficient mechanisms to grow in differentiating cells of the human epidermis, and is well adapted to human hosts. By not crossing the basement membrane, the virus evades immune surveillance; it causes no systemic immune response for most of the infection period. After a period of evading the immune system, molluscum contagiosum virus eventually induces a local response, which leads to clearance and seroconversion.

Section snippets

Clinical features

Molluscum contagiosum is a viral infection characterised by small, discrete, waxy, skin-coloured, dome-shaped papules, an average of 3–5 mm in diameter (figure 1). The number of individual lesions is generally fewer than 20 in immunocompetent hosts, but 100 or more can occasionally occur.5 When the lesions are squeezed or traumatised, a creamy, grey-white material can be extruded. Rarely, molluscum contagiosum causes lesions on the palms of the hands and soles of the feet,6 or mucous membranes

Immunocompetent patients

Molluscum contagiosum is benign and generally self-limiting. The average duration of a single lesion is about 2 months;32 however, since the lesions spread easily by autoinoculation from scratching or trauma, the mean duration of infection is about 8 months; some cases persist for 12 months or longer.4

Clinicians should weigh the potential problems of treatment against the potential complications of untreated skin lesions.33 Ablative treatments can cause pain, inconvenience, hyperpigmentation,

Epidemiology

Molluscum contagiosum has been reported to be most common in tropical climates,72 but no adequately designed epidemiological research has been published. The disease predominantly affects children, sexually active adults, and immunocompromised individuals, with no difference between the sexes. The virus is transmitted directly by skin contact; evidence also suggests occasional transmission via fomites such as bath sponges and towels.73 Rarely, school swimming pools have been implicated as a

Biology and lifecycle

Molluscum contagiosum is the only member of the Molluscipoxvirus genus in the family Poxviridae.79 It is phylogenetically distinct from other poxviruses and has several unique biological characteristics. Replication is limited to the human epidermis; the virus enhances cell mitosis and disrupts epidermal cell differentiation. Although molluscum contagiosum does not encode an epidermal growth factor homologue, expression of epidermal growth factor receptor is upregulated in infected epidermis.80

Immunology

Innate immune responses in molluscum contagiosum virus infection have not been extensively studied. Ku and colleagues145 showed that toll-like receptor 3 and toll-like receptor 9 were strongly expressed on the epidermal keratinocytes in molluscum contagiosum lesions; interferon α and tumour necrosis factor β were predominately localised adjacent to the molluscum contagiosum bodies.145 In a patient with hyper-IgE syndrome, deficiency of tyrosine kinase 2, leading to reduced downstream cytokine

Conclusion

Possible mechanisms for epidermal hyperplasia induced by molluscum contagiosum virus include epidermal growth factor receptor upregulation, vesicle anomalies, interference with cell-cycle regulation, or a combination. The clinical infection of the skin epidermis by molluscum contagiosum virus is local, subacute, and proliferative in nature. The intraepidermal location, with a lesion similar to hair follicles, endocrine secretion of immune modulators, and holocrine secretion of virus particles

Search strategy and selection criteria

We identified publications relating to molluscum contagiosum virus and molluscum contagiosum by searching Medline, PubMed, Embase, and the Cochrane Library databases with the terms “molluscum contagiosum virus” or “molluscum contagiosum” alone or in combination with the terms “pathogenesis”, “genetics”, “virology”, “history”, “immunology”, “prevalence”, “epidemiology”, and “therapy”. We also searched the reference lists of articles identified by this search strategy. Abstracts and reports from

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