LYSETというヒトの疾患遺伝子は,リンソーム酵素輸送とウイルス感染に不可欠である

関連する実験動画

Updated: Aug 29, 2025

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus

Published on: October 7, 2011

Christopher M Richards¹, Sabrina Jabs², Wenjie Qiao¹

¹Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Science (New York, N.Y.)

|September 8, 2022

まとめ

細胞タンパク質の分類とウイルス感染症において,ライソソーム酵素輸送因子 (LYSET) は極めて重要です. LYSET欠乏症はリソソムの貯蔵障害を引き起こし,SARS-CoV-2感染を悪化させる.

科学分野:

細胞生物学
分子生物学
ウイルス学

背景:

リソソームは細胞の分解に不可欠な臓器である.
マノース6酸化物 (M6P) タグ付けは,GlcNAc-1-phosphotransferase経由で酵素をリソソームに誘導する.
この経路の欠乏は,重度の溶解体貯蔵障害である粘脂症II (MLII) を引き起こします.
SARS-CoV-2 を含むキャセプシン依存ウイルスは,機能性ライソソームに依存しています.

研究の目的:

酵素の密輸に関与する新しい要因を特定する.
M6Pタグとウイルス感染におけるLYSETの役割を調査する.
LYSETに関連した疾患の分子基礎を解明する.

主な方法:

重要な遺伝子を特定するために,ゲノムスケールのCRISPRスクリーンが使用されました.
LYSETの機能はノックアウト細胞とマウスで評価された.
ウイルス感染の測定は,キャセプシン依存ウイルスを用いて行われました.
生化学的および細胞局所化研究が行われた.

主要な成果:

ゲノムスケールのCRISPRスクリーンは,SARS-CoV-2を含むキャセプシン依存ウイルス感染症に不可欠なLYSET (TMEM251) を特定しました.
LYSET欠乏症は,M6Pタグの全般的喪失とGlcNAc- 1フォスフォトランスフェラスの誤局を引き起こした.
リセット・ノックアウトマウスはMLIIのような表型を示した.
病原性ヒトLYSET変異はリソソムの分類欠陥を救えなかった.

結論:

LYSETは,M6Pのリソソーム取引機構の適切な機能に不可欠です.
LYSET変異はMLIIに似た疾患を引き起こす.
LYSETは,リソソーマルキャセプシンに依存するウイルスの重要な宿主因子である.

さらに関連する動画

Ex Vivo Infection of Murine Epidermis with Herpes Simplex Virus Type 1

Ex Vivo Infection of Murine Epidermis with Herpes Simplex Virus Type 1

Published on: August 24, 2015

Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line

Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line

Published on: February 17, 2016

関連する概念動画

Lysosomal Hydrolases

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...

Viral Replication: Lysogenic Cycle

Viral Replication: Lysogenic Cycle

The lysogenic cycle is a crucial viral replication strategy that allows bacteriophages to persist within host cells without immediately destroying them. This process is primarily observed in temperate phages, such as bacteriophage lambda (λ), which infects Escherichia coli. The cycle allows the viral genome to persist across bacterial generations while keeping host cells viable.Integration of the Viral GenomeUpon infection, bacteriophage lambda attaches to the bacterial surface and injects...

Delivery Pathways to the Lysosome

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...

Viral Replication: Lytic Cycle

Viral Replication: Lytic Cycle

Bacteriophages, or phages, are viruses that specifically infect bacteria. Among them, T-even bacteriophages, such as T4, exhibit a well-characterized lytic replication cycle in Escherichia coli (E. coli). This process ensures the rapid proliferation of the virus while ultimately leading to the destruction of the bacterial host.Attachment and DNA InjectionThe infection process begins with the recognition and binding of the T4 phage to the E. coli cell surface. Tail fibers of the phage...

Lytic Cycle of Bacteriophages

Lytic Cycle of Bacteriophages

Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the...

Viral Mutations

Viral Mutations

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...