Retrofusion of intralumenal MVB membranes parallels viral infection and coexists with exosome release

Perrin, Priscillia; Janssen, Lennert; Janssen, Hans; Broek, Bram van den; Voortman, Lenard M.; Elsland, Daphne M. van; Berlin, Ilana; Neefjes, Jacques

doi:10.1016/j.cub.2021.06.022

Cited by 31 publications

(37 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lower average pH of content release determined in our experiments compared with the interaction of VSV‐G with plasma membranes (e.g., for cell–cell fusion) reported at higher pH could be explained by the proposed mechanism of viral content release requiring ILV retrofusion in the late endosome. Many of the content release events we observe may therefore represent retrofusion events that may require a lower pH than the initial fusion with ILVs and are known to depend on the lipid composition of the late endosomes 43,49,50 . The small number (3/18) of content release events we observe at greater than pH 6.0 (Figure 3C) may represent direct virus fusion with the limiting membrane of the endosome.…”

Section: Discussionmentioning

confidence: 80%

“…Many of the content release events we observe may therefore represent retrofusion events that may require a lower pH than the initial fusion with ILVs and are known to depend on the lipid composition of the late endosomes. 43,49,50 The small number (3/18) of content release events we observe at greater than pH 6.0 (Figure 3C) may represent direct virus fusion with the limiting membrane of the endosome. It is possible content release via retrofusion is the predominant mechanism while fusion with the limiting membrane only predominates when the retrofusion mechanism has been blocked in some way or is not advantageous within a given cell or endosome.…”

Section: Characteristics Of Vsv-g Mediated Fusionmentioning

confidence: 91%

See 1 more Smart Citation

Endosomes supporting fusion mediated by vesicular stomatitis virus glycoprotein have distinctive motion and acidification

Cabot

Kiessling

White

et al. 2022

Traffic

View full text Add to dashboard Cite

Most enveloped viruses infect cells by binding receptors at the cell surface and undergo trafficking through the endocytic pathway to a compartment with the requisite conditions to trigger fusion with a host endosomal membrane. Broad categories of compartments in the endocytic pathway include early and late endosomes, which can be further categorized into subpopulations with differing rates of maturation and motility characteristics. Endocytic compartments have varying protein and lipid components, luminal ionic conditions and pH that provide uniquely hospitable environments for specific viruses to fuse. In order to characterize compartments that permit fusion, we studied the trafficking and fusion of viral particles pseudotyped with the vesicular stomatitis virus glycoprotein (VSV‐G) on their surface and equipped with a novel pH sensor and a fluorescent content marker to measure pH, motion and fusion at the single particle level in live cells. We found that the VSV‐G particles fuse predominantly from more acidic and more motile endosomes, and that a significant fraction of particles is trafficked to more static and less acidic endosomes that do not support their fusion. Moreover, the fusion‐supporting endosomes undergo directed motion.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Characteristics Of Vsv-g Mediated Fusionmentioning

confidence: 91%

Endosomes supporting fusion mediated by vesicular stomatitis virus glycoprotein have distinctive motion and acidification

Cabot

Kiessling

White

et al. 2022

Traffic

View full text Add to dashboard Cite

show abstract

“…Besides the potential contribution of FFAT motifs or palmitoylation listed above, this could occur via translocation of cytosolic annexin pools where local Ca 2+ , cholesterol or annexin-binding proteins could contribute to their association with MCS. Alternatively, annexin pools inside ILVs could be released via back fusion, a constitutive process occurring in MVBs, where ILV fuse with the perimeter LE membrane leaving the cargo at cytosolic interfaces delimited by juxtaposed membranes of MVBs and other organelles (i.e., ER) ( Gruenberg, 2020 ; Perrin et al, 2021 ). In this scenario, annexins could locally encounter a suitable Ca 2+ and lipid microenvironment that would enable them to act as interorganelle tethers.…”

Section: Discussionmentioning

confidence: 99%

Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation

Enrich

Tebar

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Membrane contact sites (MCS) are specialized small areas of close apposition between two different organelles that have led researchers to reconsider the dogma of intercellular communication via vesicular trafficking. The latter is now being challenged by the discovery of lipid and ion transfer across MCS connecting adjacent organelles. These findings gave rise to a new concept that implicates cell compartments not to function as individual and isolated entities, but as a dynamic and regulated ensemble facilitating the trafficking of lipids, including cholesterol, and ions. Hence, MCS are now envisaged as metabolic platforms, crucial for cellular homeostasis. In this context, well-known as well as novel proteins were ascribed functions such as tethers, transporters, and scaffolds in MCS, or transient MCS companions with yet unknown functions. Intriguingly, we and others uncovered metabolic alterations in cell-based disease models that perturbed MCS size and numbers between coupled organelles such as endolysosomes, the endoplasmic reticulum, mitochondria, or lipid droplets. On the other hand, overexpression or deficiency of certain proteins in this narrow 10–30 nm membrane contact zone can enable MCS formation to either rescue compromised MCS function, or in certain disease settings trigger undesired metabolite transport. In this “Mini Review” we summarize recent findings regarding a subset of annexins and discuss their multiple roles to regulate MCS dynamics and functioning. Their contribution to novel pathways related to MCS biology will provide new insights relevant for a number of human diseases and offer opportunities to design innovative treatments in the future.

show abstract

“…IFITM3 is a constituent of intraluminal vesicles, and when they are released into the extracellular space as exosomes, provides antiviral protection to neighbouring cells 78 , 79 . Furthermore, it was reported that IFITM3 reduces the ‘back-fusion’ of intraluminal vesicles with the limiting membrane of the late endosome, thereby reducing the release of intraluminal cargo into the cytoplasm 80 . As a result, IFITM3 and related proteins may promote lysosomal delivery of viral and cellular cargo travelling within late endosomes.…”

Section: Ifitm Proteinsmentioning

confidence: 99%

Lessons in self-defence: inhibition of virus entry by intrinsic immunity

Majdoul

Compton

2021

Nat Rev Immunol

View full text Add to dashboard Cite

Virus entry, consisting of attachment to and penetration into the host target cell, is the first step of the virus life cycle and is a critical ‘do or die’ event that governs virus emergence in host populations. Most antiviral vaccines induce neutralizing antibodies that prevent virus entry into cells. However, while the prevention of virus invasion by humoral immunity is well appreciated, considerably less is known about the immune defences present within cells (known as intrinsic immunity) that interfere with virus entry. The interferon-induced transmembrane (IFITM) proteins, known for inhibiting fusion between viral and cellular membranes, were once the only factors known to restrict virus entry. However, the progressive development of genetic and pharmacological screening platforms and the onset of the COVID-19 pandemic have galvanized interest in how viruses infiltrate cells and how cells defend against it. Several host factors with antiviral potential are now implicated in the regulation of virus entry, including cholesterol 25-hydroxylase (CH25H), lymphocyte antigen 6E (LY6E), nuclear receptor co-activator protein 7 (NCOA7), interferon-γ-inducible lysosomal thiol reductase (GILT), CD74 and ARFGAP with dual pleckstrin homology domain-containing protein 2 (ADAP2). This Review summarizes what is known and what remains to be understood about the intrinsic factors that form the first line of defence against virus infection.

show abstract

Retrofusion of intralumenal MVB membranes parallels viral infection and coexists with exosome release

Cited by 31 publications

References 46 publications

Endosomes supporting fusion mediated by vesicular stomatitis virus glycoprotein have distinctive motion and acidification

Endosomes supporting fusion mediated by vesicular stomatitis virus glycoprotein have distinctive motion and acidification

Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation

Lessons in self-defence: inhibition of virus entry by intrinsic immunity

Contact Info

Product

Resources

About