Natural Measles Causes Prolonged Suppression of Interleukin‐12 Production

Atabani, Sowsan; Byrnes, Adriana A.; Jaye, Assan; Kidd, IM; Magnusen, Albert F.; Whittle, Hilton; Karp, Christopher L.

doi:10.1086/321009

Cited by 91 publications

(61 citation statements)

References 55 publications

(63 reference statements)

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“…Our present finding that all four CD46 isoforms function effectively as HHV-6 receptors suggests that differential expression of the various isoforms on different cell and tissue types is unlikely to be a major determinant of HHV-6 tropism. Also of potential significance for pathogenesis is that CD46 engagement by HHV-6 causes down-modulation of IL-12 secretion by activated blood-derived macrophages, 3 as has been shown previously for MV in these same cells (39) and in vivo (40). Thus, this potentially immunosuppressive effect can be induced by distinct viruses that interact with different regions of CD46.…”

Section: Cd46 Domains Required For Hhv-6 Receptor Functionmentioning

confidence: 63%

Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Greenstone

Santoro²,

Lusso³

et al. 2002

Journal of Biological Chemistry

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We employed a quantitative cell fusion assay to identify structural domains of CD46 required for its function as a receptor for human herpesvirus 6 (HHV-6). We examined the activities of recombinant variants of CD46, including different isoforms as well as engineered truncations and molecular chimeras with decay-accelerating factor, a related protein in the family of regulators of complement activation (RCA). We observed strong receptor activity for all four CD46 isoforms, which differ in the membrane-proximal extracellular and cytoplasmic domains, indicating that the critical determinants for HHV-6 receptor activity reside outside the C-terminal portion of CD46. Analysis of the short consensus repeat (SCR) regions that comprise most of the extracellular portion of CD46 indicated a strong dependence on SCRs 2 and 3 and no requirement for SCRs 1 or 4. Fusion-inhibition studies with SCR-specific monoclonal antibodies supported the essential role of SCRs 2 and 3 in HHV-6 receptor activity. These findings contrast markedly with fusion mediated by measles virus glycoproteins for which we observed a strict dependence on SCRs 1 and 2, consistent with previous reports. These results expand the emerging notion that CD46 and other members of the RCA family are co-opted in distinct manners by different infectious pathogens.

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Section: Cd46 Domains Required For Hhv-6 Receptor Functionmentioning

confidence: 63%

Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Greenstone

Santoro²,

Lusso³

et al. 2002

Journal of Biological Chemistry

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“…Interestingly, infection of canine DCs with canine distemper virus, a close relative of MV also using CD150 as the entry receptor, equally decreases the surface levels of HLA-DR, CD80, and CD86 47 , suggesting that viral interaction with CD150 may have similar consequences for different Moribilliviruses in their natural hosts. Another hallmark of MV-induced immunosuppression, inhibition of IL-12 production, was reported in MV-infected children 48 , rhesus macaques during measles 49 , wt MV-infected mice expressing human SLAM 50 and primary human monocytes infected by MV 51 . The production of IL-12 was also impaired after CD150/CD150 self-ligation in human DCs 46 and an activation of Akt was shown to be followed by a decrease in IL-12 production 52,53 .…”

Section: Discussionmentioning

confidence: 91%

Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response

et al. 2015

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Measles virus (MV) is highly contagious pathogen, which causes a profound immunosuppression, resulting in high infant mortality. This virus infects dendritic cells (DCs) following the binding of MV hemagglutinin (MV-H) to CD150 receptor and alters DC functions by a mechanism that is not completely understood. We have analyzed the effect of MV-H interaction with CD150-expressing DCs on the DC signaling pathways and consequent phenotypic and functional changes in the absence of infectious context. We demonstrated that contact between CD150 on human DCs and MV-H expressed on membrane of transfected CHO cells was sufficient to modulate the activity of two major regulatory pathways of DC differentiation and function: to stimulate Akt and inhibit p38 MAPK phosphorylation, without concomitant ERK1/2 activation. Furthermore, interaction with MV-H decreased the expression level of DC activation markers CD80, CD83, CD86, and HLA-DR and strongly downregulated IL-12 production but did not modulate IL-10 secretion. Moreover, contact with MV-H suppressed DC-mediated T-cell alloproliferation, demonstrating profound alteration of DC maturation and functions. Finally, engagement of CD150 by MV-H in mice transgenic for human CD150 decreased inflammatory responses, showing the immunosuppressive effect of CD150-MV-H interaction in vivo. Altogether, these results uncover novel mechanism of MV-induced immunosuppression, implicating modulation of cell signaling pathways following MV-H interaction with CD150-expressing DCs and reveal anti-inflammatory effects of CD150 stimulation.

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“…Both disruption of mucosal surfaces and the immunosuppression associated with measles virus predispose to secondary infection, which is thought to occur in over half of children with measles associated pneumonia (2,24,25). We found that the disease severity was associated with the higher peripheral leukocyte, neuthrophil counts and higher serum CRP levels.…”

Section: Discussionmentioning

confidence: 63%

Clinical characteristics, complications and prognosis of seventy-nine measles cases Yetmişdokuz kızamık olgusunda klinik özellikler, komplikasyonlar ve prognoz

Tuğba;TANIR¹

2006

Ankara Üniversitesi Tıp Fakültesi Mecmuası

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DAHİLİ BİLİMLER / MEDICAL SCIENCES Araştırma Yazısı / Original ArticleM easles is a highly contagious acute viral illness characterized by a distinct exanthem, pathognomic enanthem, accompanied by the classical triad of cough, coryza and conjunctivitis (1). Measles immunization is highly effective in preventing measles and reduces mortality in immunized children by 40-75% (2). The first measles vaccination is given to infants at 9 th months according to the Ministry of Health's recomendations in Turkey. Measles related deaths account for about 10% of all deaths in children under the age of 5 years in developing countries (3). Acute measles infection at an early Aim: To investigate the age distribution, clinical presentations, laboratory and radiological findings, complications and prognosis of measles in children. Materials and Methods:The children with the clinical diagnosis of measles which was confirmed by a sensitive enzyme immunoassay for measles IgM antibody were evaluated comprehensively aspect to complication of measles (i.e. pneumonia, otitis media, encephalitis). Results: The ages of the 79 patients with measles ranged from 1 to 180 months. The severity of the disease was significantly correlated with the younger age (p<0.001), higher levels of blood neuthrophil counts and serum C-Reactive Protein (CRP) (p<0.05). The most common complications were pneumonia (75%) and encephalitis (9%). Three (3,8%) patients died due to the complications. Conclusion: It was found that the severity of measles and the rate of complications are high especially in infancy. Secondary bacterial pneumonia is the most common complications and also responsible for the severity of measles. Acute measles encephalitis is not infrequent. Infancy, very severe pneumonia, malnutrition and compromised immunity are the major factors which increase mortality. Key words: measles, children, complicationsAmaç: Kızamığın çocuklarda yaş dağılımını, klinik ve laboratuar özelliklerini, radyolojik bulgularını, yan etkilerini ve prognozu değerlendirmek amaçlandı. Gereç ve Yöntem: Klinik olarak kızamık tanısı konulan ve kızamık IgM antikor mikroELISA yön-temi ile de tanısı kesinleşen olgular kızamığın yan etkileri (alt solunum yolu enfeksiyonu, orta kulak iltihabı, ensefalit) açısından ayrıntılı olarak değerlendirildi. Bulgular: Yetmiş dokuz olgunun yaşları 1-180 ay arasında değişmekteydi. Hastalığın şiddeti yaşın küçük olması (p<0.001), kan nötrofil sayısındaki ve CRP'deki yükseklik ile (p<0.05) ciddi olarak ilişkili bulundu. En sık görülen yan etki pnömoni (%75) ve ensefalit (%9) idi. Üç (%3,8) olgu kızamık yan etkilerinden dolayı kaybedildi. Tartışma: Özellikle bebeklik dönemindeki çocukların, kızamığın şiddeti ve yan etkileri açısından daha duyarlı oldukları saptandı İkincil bakteriyel alt solunum yolu enfeksiyonu oldukça sık ve ayrıca hastalığın ciddiyetinden sorumlu faktör olarak saptandı. Akut kızamık ensefalitinin de düşünüldüğü kadar ender olmadığı görüldü. Bebeklik dönemi, çok ciddi alt solunum yolu, malnütrisyon ve immun baskılanma morta...

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Natural Measles Causes Prolonged Suppression of Interleukin‐12 Production

Cited by 91 publications

References 55 publications

Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Human Herpesvirus 6 and Measles Virus Employ Distinct CD46 Domains for Receptor Function

Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response

Clinical characteristics, complications and prognosis of seventy-nine measles cases Yetmişdokuz kızamık olgusunda klinik özellikler, komplikasyonlar ve prognoz

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