Antibodies to Molluscum Contagiosum Virus in the General Population and Susceptible Patients

Watanabe, Takahiro; Nakamura, Koichiro; Wakugawa, Motoshi; Kato, Atsushi; Nagai, Yoshinori; Shioda, Tatsuo; Iwamoto, Aikichi; Tamaki, Kunihiko

doi:10.1001/archderm.136.12.1518

Cited by 48 publications

(35 citation statements)

References 19 publications

(28 reference statements)

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“…Discussion MCV is a dermatotropic poxvirus that causes benign skin neoplasms in humans (26). MCV is a common and worldwide infection, and is an opportunistic infection of immunocompromised patients (56)(57)(58)(59). MCV is understudied due to the lack of an animal model for disease or a tissue culture-based propagation system.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus

Randall

Biswas

Selen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Apoptosis, NF-κB activation, and IRF3 activation are a triad of intrinsic immune responses that play crucial roles in the pathogenesis of infectious diseases, cancer, and autoimmunity. FLIPs are a family of viral and cellular proteins initially found to inhibit apoptosis and more recently to either up-or down-regulate NF-κB. As such, a broad role for FLIPs in disease regulation is postulated, but exactly how a FLIP performs such multifunctional roles remains to be established. Here we examine FLIPs (MC159 and MC160) encoded by the molluscum contagiosum virus, a dermatotropic poxvirus causing skin infections common in children and immunocompromised individuals, to better understand their roles in viral pathogenesis. While studying their molecular mechanisms responsible for NF-κB inhibition, we discovered that each protein inhibited IRF3-controlled luciferase activity, identifying a unique function for FLIPs. MC159 and MC160 each inhibited TBK1 phosphorylation, confirming this unique function. Surprisingly, MC159 coimmunoprecipitated with TBK1 and IKKe but MC160 did not, suggesting that these homologs use distinct molecular mechanisms to inhibit IRF3 activation. Equally surprising was the finding that the FLIP regions necessary for TBK1 inhibition were distinct from those MC159 or MC160 regions previously defined to inhibit NF-κB or apoptosis. These data reveal previously unappreciated complexities of FLIPs, and that subtle differences within the conserved regions of FLIPs possess distinct molecular and structural fingerprints that define crucial differences in biological activities. A future comparison of mechanistic differences between viral FLIP proteins can provide new means of precisely manipulating distinct aspects of intrinsic immune responses.host-pathogen interactions | immune evasion I FN-β provides an important defense against viral infections (1, 2). The pathway leading to IFN-β production is well characterized. By-products of viral infection, such as dsRNA, are detected by upstream cellular sensors, including retinoic acidinducible gene 1 (RIG-I), melanoma differentiation-associated factor gene 5 (MDA5), and STING. RIG-I and MDA5 proteins then interact with mitochondrial antiviral signaling (MAVS) adaptor protein to trigger MAVS activation (3-8). The TNF receptor-associated factor 3 (TRAF3) adaptor protein is recruited to this complex, resulting in the activation of the kinase complex TANK-binding kinase 1 (TBK1)-IκB kinase e (IKKe) (9-11). Alternatively, the STING molecule activates TBK1-IKKe (12, 13). In either case, TBK1-IKKe phosphorylates and activates IFN regulatory factor (IRF) transcription factor proteins (11), which migrate to the nucleus to bind to the IFN-β enhancer. IFN-β is secreted and binds to the IFN receptor (IFNR). This initiates a second signaling cascade in infected and neighboring cells, which promotes expression of IFN-α and IFN-stimulated genes whose products contribute to an antiviral state.Identification of the above members of the IFN-β signal transduction pathway also resul...

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Section: Resultsmentioning

confidence: 99%

Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus

Randall

Biswas

Selen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…This similar association of MC between AD and non-AD individuals, of course, does not rule out the possibility that MC is exacerbated by concomitant AD, although we could not address this point in the present study protocol. MC lesions take several months to years to resolve spontaneously [11,23,24], but the presence of concomitant AD is the most significant factor associated with relapse and the risk of treatment failure of MC [11,25,26]. Children with AD and MC may visit clinics more frequently due to the easily spread or persistent tendency of the lesions, which may cause a referral bias in a hospital-based study.…”

Section: Discussionmentioning

confidence: 99%

Are lifetime prevalence of impetigo, molluscum and herpes infection really increased in children having atopic dermatitis?

Hayashida

Norihiro

Uchi

et al. 2010

Journal of Dermatological Science

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“…30,31,34 However, the extent of this association has not been quantified clinically, and different studies come to different conclusions. In this study, 24.2% of the patients were diagnosed with concomitant AD at the time of diagnosis of the MC.…”

Section: Discussionmentioning

confidence: 99%

“…29,30 The increased prevalence and severity of MC in this patient population have been linked to the relative suppression of the helper T-cell type 1 responses in acute skin lesions of AD. [31][32][33][34] MC has also been associated with systemic iatrogenic immunosuppression from administration of corticosteroids and chemotherapy. 35 The epidemiology and features of clinical presentation of MC infection in children and the association of MC to immunosuppression and AD are poorly understood.…”

mentioning

confidence: 99%

The epidemiology of molluscum contagiosum in children

Dohil

Lin

Lee

et al. 2006

Journal of the American Academy of Dermatology

145

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Antibodies to Molluscum Contagiosum Virus in the General Population and Susceptible Patients

Cited by 48 publications

References 19 publications

Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus

Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus

Are lifetime prevalence of impetigo, molluscum and herpes infection really increased in children having atopic dermatitis?

The epidemiology of molluscum contagiosum in children

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