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Peptide presentation by bat MHC class I provides new insight into the antiviral immunity of bats

يقدم عرض الببتيد بواسطة BAT MHC الفئة الأولى نظرة جديدة على المناعة المضادة للفيروسات للخفافيش
Authors: Dan Lü; Kefang Liu; Di Zhang; Can Yue; Qiong Lu; Hao Cheng; Liang Wang; +5 Authors

Peptide presentation by bat MHC class I provides new insight into the antiviral immunity of bats

Abstract

Les chauves-souris abritent de nombreux virus zoonotiques, y compris des virus hautement pathogènes chez l'homme et d'autres mammifères, mais elles sont généralement asymptomatiques chez les chauves-souris. Pour mieux comprendre l'immunité antivirale des chauves-souris, nous avons dépisté et identifié une série de peptides de liaison au complexe majeur d'histocompatibilité (CMH) I Ptal-N *01:01 des chauves-souris dérivés de quatre virus différents transmis par les chauves-souris, à savoir le virus Hendra (HeV), le virus Ebola (EBOV), le coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV) et le virus pseudo-grippal H17N10. Les structures de Ptal-N *01:01 présentent des caractéristiques de présentation peptidique inhabituelles en ce que l'insertion de l'acide aminé 3 spécifique à la chauve-souris (aa) permet l '« ancrage de surface » serré du P1-Asp dans la poche A du MHC I de la chauve-souris. Comme les positions d'ancrage primaires classiques, les poches B et F de Ptal-N *01:01 présentent également des conformations non conventionnelles, qui contribuent à des motifs peptidiques inhabituels et à une présentation peptidique distincte. Notamment, les caractéristiques de bat MHC I peuvent être partagées par MHC I à partir de divers marsupiaux. Notre étude met en lumière l'immunité adaptative des chauves-souris et pourrait être bénéfique pour le développement futur de vaccins contre les virus transmis par les chauves-souris ayant un impact élevé sur les humains.

Los murciélagos albergan muchos virus zoonóticos, incluidos virus altamente patógenos de humanos y otros mamíferos, pero generalmente son asintomáticos en los murciélagos. Para comprender mejor la inmunidad antiviral de los murciélagos, examinamos e identificamos una serie de péptidos de unión al complejo mayor de histocompatibilidad (MHC) I Ptal-N *01:01 de murciélagos derivados de cuatro virus diferentes transmitidos por murciélagos, es decir, el virus Hendra (HeV), el virus del Ébola (EBOV), el coronavirus del síndrome respiratorio de Oriente Medio (MERS-CoV) y el virus similar a la gripe H17N10. Las estructuras de Ptal-N*01:01 muestran características de presentación peptídica inusuales en el sentido de que la inserción de 3-aminoácidos (aa) específica de murciélago permite el "anclaje superficial" apretado de P1-Asp en el bolsillo A del MHC I. Como las posiciones de anclaje primarias clásicas, los bolsillos B y F de Ptal-N *01:01 también muestran conformaciones no convencionales, que contribuyen a motivos peptídicos inusuales y presentación peptídica distinta. En particular, las características de Bat MHC I pueden ser compartidas por MHC I de varios marsupiales. Nuestro estudio arroja luz sobre la inmunidad adaptativa de los murciélagos y puede beneficiar el desarrollo futuro de vacunas contra los virus transmitidos por murciélagos de alto impacto en los seres humanos.

Bats harbor many zoonotic viruses, including highly pathogenic viruses of humans and other mammals, but they are typically asymptomatic in bats. To further understand the antiviral immunity of bats, we screened and identified a series of bat major histocompatibility complex (MHC) I Ptal-N*01:01-binding peptides derived from four different bat-borne viruses, i.e., Hendra virus (HeV), Ebola virus (EBOV), Middle East respiratory syndrome coronavirus (MERS-CoV), and H17N10 influenza-like virus. The structures of Ptal-N*01:01 display unusual peptide presentation features in that the bat-specific 3-amino acid (aa) insertion enables the tight "surface anchoring" of the P1-Asp in pocket A of bat MHC I. As the classical primary anchoring positions, the B and F pockets of Ptal-N*01:01 also show unconventional conformations, which contribute to unusual peptide motifs and distinct peptide presentation. Notably, the features of bat MHC I may be shared by MHC I from various marsupials. Our study sheds light on bat adaptive immunity and may benefit future vaccine development against bat-borne viruses of high impact on humans.

تأوي الخفافيش العديد من الفيروسات الحيوانية المنشأ، بما في ذلك الفيروسات شديدة الإمراض لدى البشر والثدييات الأخرى، لكنها عادة ما تكون بدون أعراض في الخفافيش. لمزيد من فهم المناعة المضادة للفيروسات للخفافيش، قمنا بفحص وتحديد سلسلة من معقد التوافق النسيجي الرئيسي للخفافيش (MHC) I Ptal - N *01:01 - الببتيدات الملزمة المشتقة من أربعة فيروسات مختلفة تنقلها الخفافيش، أي فيروس هيندرا (HEV)، وفيروس إيبولا (EBOV)، وفيروس كورونا لمتلازمة الشرق الأوسط التنفسية (MERS - CoV)، وفيروس H17N10 الشبيه بالإنفلونزا. تعرض هياكل Ptal - N *01:01 ميزات عرض الببتيد غير العادية من حيث أن إدخال الأحماض الأمينية الثلاثة الخاصة بالخفافيش (aa) يتيح "التثبيت السطحي" الضيق لـ P1 - Asp في الجيب A من BAT MHC I. نظرًا لأن مواضع التثبيت الأساسية الكلاسيكية، فإن جيوب B و F من Ptal - N *01:01 تُظهر أيضًا توافقًا غير تقليدي، مما يساهم في زخارف الببتيد غير العادية وعرض الببتيد المتميز. والجدير بالذكر أنه يمكن مشاركة ميزات BAT MHC I من قبل MHC I من مختلف الجرابيات. تسلط دراستنا الضوء على المناعة التكيفية للخفافيش وقد تفيد في تطوير لقاح مستقبلي ضد الفيروسات التي تنقلها الخفافيش والتي لها تأثير كبير على البشر.

Keywords

QH301-705.5, Epidemiology, Major histocompatibility complex, FOS: Health sciences, General Biochemistry, Genetics and Molecular Biology, Hendra Virus, Ebola virus, Chiroptera, Virology, Health Sciences, Genetics, Animals, RNA Viruses, Biology (General), Biology, Antigen Presentation, General Immunology and Microbiology, General Neuroscience, Histocompatibility Antigens Class I, H1N1, Immunity, Ebola Virus Research and Outbreaks, Virus, Infectious Diseases, Immune system, FOS: Biological sciences, Antigen, Host-Pathogen Interactions, MHC class I, Medicine, Influenza Virus Research and Epidemiology, General Agricultural and Biological Sciences, Viral Hemorrhagic Fevers and Zoonotic Infections, Research Article

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
31
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Top 10%
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