Mx1は,抗ウイルス耐性および致死性インフルエンザへの先天的な経路を明らかにします

Padmini S Pillai¹, Ryan D Molony¹, Kimberly Martinod²

¹Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.

Science (New York, N.Y.)

|April 23, 2016

まとめ

インフルエンザAウイルス (IAV) 耐性が低下した高齢者は,細菌感染が増加します. これらの脆弱な集団における死亡率は,ウイルス負荷ではなく,カスパースに依存する病理と関連しています.

科学分野:

免疫学
ウイルス学
ゲロントロジー

背景:

インフルエンザAウイルス (IAV) は,年配の成人に不釣り合いな影響を及ぼし,年配の成人に著しい死亡率をもたらします.
高齢者のIAVに感染した単細胞は,インターフェロン産生が低下しているが,炎症性反応は無傷である.
年齢に関係するIAVの脆弱性を理解するには,宿主-病原体の相互作用を in vivo で調べる必要があります.

研究の目的:

IAV感染の文脈における抗ウイルス反応の障害のインビボの結果を調査する.
IAV感染時の高齢者の死亡率増加の原因となるメカニズムを特定する.
IAVの病原性における細菌の共感染と炎症体の活性化の役割を明らかにする.

主な方法:

ヒトのインターフェロン誘発抗ウイルスエフェクターである機能的なMx遺伝子を発現するマウスを利用した.
MavsとTlr7に欠陥があるマウスモデルを用いて弱まった抗ウイルス抵抗を模倣した.
評価されたウイルス負荷,細菌負荷,炎症体活性化 (カスペーゼ-1/11) および中性粒子の依存性組織損傷.

主要な成果:

抵抗力が低下したマウス (MavsとTlr7欠乏症) は,呼吸器のバクテリアの負荷が増加した.
死亡率は,ウイルス負荷またはMyD88依存のシグナリングとは無関係でした.
死亡率は,細菌負荷,カスパース-1/11活性化,中性粒子の媒介による組織損傷に決定的に依存していた.

結論:

抗ウイルス防御機能が低下した個体では,重度のIAV疾患に対する感受性は,カスパースに依存する病理によって引き起こされ,細菌による共感染によって悪化します.
これは,脆弱な集団におけるIAV関連死亡における炎症体活性化と二次細菌感染症の重要な役割を強調しています.
カスパースに依存する経路をターゲットにすることで,インフルエンザの流行中に高齢者の重篤なアウトカムを緩和する治療戦略を提供することができる.

さらに関連する動画

08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

11.0K

07:55

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies

Published on: August 29, 2017

12.3K

関連する概念動画

01:29

Immune Response Against Viral Pathogens

2.5K

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...

2.5K

01:27

Influenza

Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...

02:28

Leaky Scanning

5.8K

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...

5.8K

01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...

00:36

Viral Mutations

40.7K

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...

40.7K

00:57

Viral Recombination

25.5K

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.