COVID-19 researchGene: BECN1
Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): BECN1 encodes the beclin1 protein which is an established regulator of the autophagic pathway. Autophagy is a key mechanism against invading bacteria, parasites, and viruses in innate immune cells including monocytes/macrophages, dendritic cells and neutrophils (reviewed in Tao et al. 2020). Viral proteins such as HIV-1 Nef, ICP34.5 of HSV-1 and M11 of MHV-68 have been shown to interact with Beclin-1 and block the late stage of autophagy, thereby protecting viral particles from degradation (Kyei et al 2009; Orvedahl et al. (2007); Ku et al. (2008)
PMID:32265919 Tao et al. 2020 (review) - Autophagy is a key mechanism against invading bacteria, parasites, and viruses in innate immune cells including monocytes/macrophages, dendritic cells (conventional dendritic cells-cDCs and plasmacytoid dendritic cells-pDCs) and neutrophils. BECN1 encodes beclin1 protein which is an established regulator of the autophagic pathway. Viral proteins may target BECN1 to inhibit autophagy.
PMID: 19635843 Kyei et al. (2009) - A series of experiments showed that the Nef protein of HIV inhibits the autophagic maturation pathway (fig 5). Macrophages transfected with Nef-GFP showed colocalization of Nef with Beclin-1 and the two proteins were shown to physically interact in immunoprecipitation experiments (Fig6).
PMID: 18248095 Ku et al. (2008) - In NIH3T3 cell culture studies, the M11, a viral BCL-2 of murine gamma herpesvirus 68 was shown to bind Beclin-1 and to inhibit to inhibit Beclin-1 mediated autophagy (Fig 4).
PMID: 18005679 Orvedahl et al. (2007) - The authors used coimmunoprecipitation experiments in both HEK293 cells and embryonic stem cells to show that the neurovirulence protein of Herpes simplex virus (HSV)-1, ICP34.5, binds to the C terminus of BECN1 (Fig 2). In MCF7 stably expressing BECN1cells, transfection of the ICP34.5 inhibited autophagy (Fig 2). Mutant HSV-1 lacking the ICP34.5 BECN1-binding domain failed to inhibit autophagy in primary sympathetic neurons (Fig 5A) and had impaired ability to cause lethal encephalitis in mice (Fig 6) .
Created: 28 May 2020, 3:29 p.m. | Last Modified: 28 May 2020, 3:29 p.m.
Panel Version: 0.349
Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
Created: 28 May 2020, 12:36 p.m. | Last Modified: 28 May 2020, 12:36 p.m.
Panel Version: 0.336
gene: BECN1 was added gene: BECN1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber Mode of inheritance for gene: BECN1 was set to Unknown