Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014

Sinclair, Catriona; Gaunt, Eleanor; Simmonds, Peter; Broomfield, D; Nwafor, N; Wellington, Louise; Templeton, Kate; Willocks, Lorna; Schofield, O.M.V.; Harvala, Heli

doi:10.2807/1560-7917.es2014.19.12.20745

Cited by 96 publications

(74 citation statements)

References 19 publications

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“…However, since the CV-A16-related outbreak of HFMD occurred in England in 1994 (3), accumulating evidence has demonstrated that CV-A16 infection can also cause severe neurological complications (4) and death (5,6). Recently, CV-A6 infection has also been increasingly associated with HFMD outbreaks around the world (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Furthermore, EV-D68 has been linked to severe respiratory disease worldwide in recent years.…”

mentioning

confidence: 99%

Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68

Rui

Wang

et al. 2017

J Virol

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Coxsackievirus A16 (CV-A16), CV-A6, and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated. In this study, we discovered that the 3C pro proteins from CV-A16, CV-A6, and EV-D68 bind melanoma differentiation-associated gene 5 (MDA5) and inhibit its interaction with MAVS. Consequently, MDA5-triggered type I interferon (IFN) signaling in the retinoic acid-inducible gene I-like receptor (RLR) pathway was blocked by the CV-A16, CV-A6, and EV-D68 3C pro proteins. Furthermore, the CV-A16, CV-A6, and EV-D68 3C pro proteins all cleave transforming growth factor ␤-activated kinase 1 (TAK1), resulting in the inhibition of NF-B activation, a host response also critical for Toll-like receptor (TLR)-mediated signaling. Thus, our data demonstrate that circulating HFMD-associated CV-A16 and CV-A6, as well as severe respiratory disease-associated EV-D68, have developed novel mechanisms to subvert host innate immune responses by targeting key factors in the RLR and TLR pathways. Blocking the ability of 3C pro proteins from diverse enteroviruses and coxsackieviruses to interfere with type I IFN induction should restore IFN antiviral function, offering a potential novel antiviral strategy.IMPORTANCE CV-A16, CV-A6, and EV-D68 are emerging pathogens associated with hand, foot, and mouth disease and pediatric respiratory disease worldwide. The pathogenic mechanisms of these viruses are largely unknown. Here we demonstrate that the CV-A16, CV-A6, and EV-D68 3C pro proteins block MDA5-triggered type I IFN induction. The 3C pro proteins of these viruses bind MDA5 and inhibit its interaction with MAVS. In addition, the CV-A16, CV-A6, and EV-D68 3C pro proteins cleave TAK1 to inhibit the NF-B response. Thus, our data demonstrate that circulating HFMDassociated CV-A16 and CV-A6, as well as severe respiratory disease-associated EV-D68, have developed a mechanism to subvert host innate immune responses by simultaneously targeting key factors in the RLR and TLR pathways. These findings indicate the potential merit of targeting the CV-A16, CV-A6, and EV-D68 3C pro proteins as an antiviral strategy.KEYWORDS MDA5, TAK1, MAVS, 3C protease, CV-A16, CV-A6, EV-D68, HFMD, innate immune response

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confidence: 99%

Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68

Rui

Wang

et al. 2017

J Virol

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“…Esta distribución extensa de las lesiones se asocia a un serotipo CA6 y a factores de riesgo como edad menor de 3 años y dermatitis atópica (2,13) . Dichas presentaciones se conocen como las formas atípicas de EMPB, y difieren en que afectan el área perioral, extremidades y torso, adicional a las manifestaciones clásicas del EMPB, con un exantema eritematoso papular que ocupan más del 10% de superficie corporal total (SCT), y menor compromiso oral (4,14) . Cuatro morfologías distintas caracterizan este exantema atípico (4) : a).…”

Section: Discussionunclassified

Enfermedad de mano, pie y boca en un hospital del Callao, 2016

Rodríguez-Zúñiga

Vértiz-Gárate

Cortez-Franco

et al. 2017

Rev Peru Med Exp Salud Publica

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RESUMENLa enfermedad de mano, pie y boca (EMPB) es una enfermedad exantemática viral, causada principalmente por Coxsackie A16, con una sintomatología típica consistente en fiebre; exantema pápulo-vesicular en manos, pies y genitales; y un enantema ulceroso en boca. En el verano del 2016 se presentó una diversidad de casos en un hospital del Callao en niños y adultos, con una sintomatología compatible con EMPB; el diagnóstico fue clínico, se aplicó terapia de soporte con resolución final de síntomas. En la última década se han presentado reportes en algunos países con una afectación atípica causada por el Coxsackie A6, produciendo lesiones más extensas y en adultos. Sin embargo, el diagnóstico sigue siendo clínico, solo necesitando confirmación virológica en casos atípicos o cuando el diagnóstico no es claro. La importancia de este reporte radica en describir los casos del Callao ocurridos en el verano del 2016, para servir de apoyo a los profesionales de la salud en el diagnóstico y manejo de pacientes con similar sintomatología. HAND, FOOT, AND MOUTH DISEASE IN A HOSPITAL IN CALLAO IN 2016 ABSTRACTHand, foot, and mouth disease (HFMD) is an exanthematous viral disease caused mainly by Coxsackie A16 with a typical symptomatology of fever, papulovesicular rash on the hands, feet, and genitals, and an ulcerous enanthem in the mouth. In the summer of 2016, a variety of cases presented at a hospital in Callao in children and adults with a symptomatology consistent with HFMD. A clinical diagnosis was made, and support therapy was applied, resulting in the resolution of symptoms. In the last decade, reports have emerged in some countries of an atypical involvement caused by Coxsackie A6, producing lesions that are more widely distributed in adults. However, the diagnosis remains clinical, only requiring virological confirmation in atypical cases or when the diagnosis is unclear. The importance of this report stems from its description of the cases in Callao that occurred in the summer of 2016 and serve as an example for health professionals in the diagnosis and management of patients with similar symptomatology.

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“…En sık etken coxsackievirus A16 olup, diğer enterovirüsler ile de hastalık oluşabilmektedir (1)(2)(3)(4)(5) . En sık görülen klinik bulgular; ateş, avuç içi ve ayak tabanlarında küçük veziküller ve oral mukoza ve dilde aftöz lezyonlardır.…”

Section: Discussionunclassified

“…Bu durum, hastane personelinin döküntülü hastaya yaklaşımında koruyucu önlemlerin önemini göstermektedir. Sıklıkla coxsackievirus A6'nın neden olduğu bir atipik el-ayak-ağız hastalığı formu 2008 yılında Asya ve Avrupa'da, 2011 yılında ise Amerika'da tanımlan-mıştır (2,3,5,6) . Bu formda klasik forma göre cilt lezyonları daha belirgin olup, vezikülöbüllöz lezyonlar sık-lıkla el ve ayak dorsal kesimlerinde, gövde ve boyunda daha belirgindir.…”

Section: Discussionunclassified

“…Atopik dermatitli hastalarda lezyonlar ekzema herpetikuma benzer ve "eczema coxsackium" olarak adlandırılır. Literatürdeki atipik el-ayakağız hastalığı olguları incelendiğinde, yaklaşık %30 kadar olgunun başvuruda ekzema herpetikum düşü-nülerek asiklovir tedavisi aldığı görüldü (2)(3)(4)(5)(6)(7) . Bizim olgumuz da başlangıçta vezikülöbüllöz lezyonların yaygınlığı nedeni ile ekzema herpetikum düşünüle-rek asiklovir tedavisi aldı.…”

Section: Discussionunclassified

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A case with atypical hand-mouth-foot disease accompanying with onicomadesis and a small-scale outbreak

Kocabaş¹,

Karbuz²,

Doğulu³

et al. 2017

BUCH

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ÖZEl-ayak-ağız hastalığı enterovirüslerden sıklıkla Coxsackievirus A16 ve enterovirüs 71'in neden olduğu bir hastalık olup, toplumda salgınlara yol açabilmektedir. Son zamanlarda klasik el-ayak-ağız hastalığından farklı özellikleri içeren bir atipik form tanımlanmıştır. Bu atipik formda klasik hastalıktan farklı olarak cilt lezyonlarının daha fazla dorsal yüzleri etkilemesi, gövde ve boyunda daha fazla yoğunlaşması, ülse-re ve büllöz formda olması, kabuklanma ile soyulmanın tipik olması ve onikomadezis ile sık birliktelik görülmektedir. Burada, ekzema herpetikum kliniği ile başvuran ve izlemde kısa sürede küçük bir salgına yol açan ve onikomadezis ile iyileşen 17 aylık bir atipik el-ayak-ağız hastalığı olgusu sunulmuştur. Bu olgu sunumu ile ekzema herpetikum ön tanısı ile izlenen ve herpesvirüs için yapılan viral testleri negatif saptanan özellikle 2 yaş altındaki olgularda ayırıcı tanıda atipik enteroviral hastalığın düşünül-mesi vurgulanmak istenmiştir. Atipik hastalık bulgularının iyi bilinmesi gereksiz asiklovir kullanımının önüne geçebilir. Ayrıca koruyucu önlemlerin alınması ile nozokomiyal ve toplumsal salgınların önlenmesi sağlanabilecektir. Anahtar kelimeler: Atipik el-ayak-ağız hastalığı, enterovirüs, ekzema herpetikum, onikomadezis ABSTRACTHand-mouth-foot disease is generally caused by Coxsackievirus A16 and Enterovirus 71, which are subtypes of enteroviruses, and it can lead to outbreaks in the people. Recently, an atypical form of disease has been described which consists of different characteristics from classical form. It differs from the classical form of disease with widespread distribution of vesiculobullous skin lesions on the trunk and neck, high rate of ulcerate and bullous formation, crusted and scabbed lesions and onychomadesis. Herein, we reported a 17-month-old child with atypical hand-foot-mouth disease. He was firstly diagnosed with eczema herpeticum, lead to a small outbreak, and healed with onicomadesis. We pointed out atypical enteroviral diseases in infants especially presented with eczema herpeticum and negative tests for herpesviruses. Unnecessary use of acyclovir could be avoided if atypical manifestations of disease are well known. Also, hospital and community outbreaks can be prevented by taking protective measures.

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Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014

Cited by 96 publications

References 19 publications

Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68

Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68

Enfermedad de mano, pie y boca en un hospital del Callao, 2016

A case with atypical hand-mouth-foot disease accompanying with onicomadesis and a small-scale outbreak

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