SARS-CoV-1 3a binds the lysosomal membrane

Stable Identifier
R-HSA-9686338
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
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Severe acute respiratory syndrome-associated coronavirus type 1 (SARS-CoV-1) open reading frame-3a has been implicated in host cell death pathways. Receptor interacting serine/threonine protein kinase 3 (RIPK3) was found to induce oligomerization of SARS-CoV-1 3a after co-transfection of viral 3a and RIPK3 in human embryonic kidney 293 (HEK293) that do not express endogenous RIPK3 or MLKL (Yue Y et al. 2018). Confocal imaging showed that co-expressed SARS-CoV-1 3a and RIPK3 co-localized with lysosomal-associated membrane protein 1 (LAMP1) in HeLa cells (Yue Y et al. 2018). Quantification of colocalization revealed that 3a likely targets RIPK3 to lysosomes. Further, a lysosomal galectin puncta assay showed that SARS-CoV-1 3a caused lysosomal membrane permeabilization. In addition, the SARS-CoV-1 3a-mediated release of cathepsins from lysosomes in HEK293 cells (Yue Y et al. 2018). Thus, RIPK3 is thought to induce oligomerization of SARS-CoV-1 3a, which facilitates membrane insertion and ion channel functionality of SARS-CoV-1 3a (Yue Y et al. 2018).

Literature References
PubMed ID Title Journal Year
30185776 SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death

Yue, Y, Nabar, NR, Shi, CS, Kamenyeva, O, Xiao, X, Hwang, IY, Wang, M, Kehrl, JH

Cell Death Dis 2018
Participants
Participates
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
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