Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

Abstract

Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19.

COVID‐19 infection, progression, and vaccination: Focus on obesity and related metabolic disturbances

“…Upon binding, the host protease, transmembrane protease serine 2 (TMPRSS2), expressed on the cell membrane, cleaves S into the S1 and S2 subunits to activate S to facilitate virus‐host cell fusion 48 . In the endosomal pathway, SARS‐CoV‐2 also binds ACE2, but instead of activating TMPRSS2, SARS‐CoV‐2 is internalized via clathrin‐mediated endocytosis 49 . Thus, in both pathways, ACE2 plays an essential role to induce viral cell invasion.…”

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19

“…BMP prevents the formation of 7KC in murine macrophagic RAW264.7 cells [ 101 ]. Recently, it has been suggested that BMP could be useful in the prevention of SARS-CoV-2 infection [ 102 ]. It is hypothesised that BMP, which is present in the endosomes and is involved in the intracellular cholesterol trafficking, could act on the SARS-CoV-2 viral cycle and reduce virus production.…”

Acid Sphingomyelinase, a Lysosomal and Secretory Phospholipase C, Is Key for Cellular Phospholipid Catabolism

“…It has been furthermore suggested that the unique anionic lysosomal lipid BMP plays an important role in viral infections [194] and that the secretory ASM is required for the virus entry at the plasma membranes [190], reducing their high SM levels and leading to an internalization of the virus [195]. It has also been shown that sphingosine could be exploited as an antiviral compound.…”