scholarly journals Entropic Forces Drive Clustering and Spatial Localization of Influenza A M2 During Viral Budding

2018 ◽  
Author(s):  
Jesper J. Madsen ◽  
John M. A. Grime ◽  
Jeremy S. Rossman ◽  
Gregory A. Voth
Keyword(s):  
Host Cell ◽  
Influenza A ◽  
Spatial Localization ◽  
Membrane Curvature ◽  
Infected Host ◽  
Membrane Remodeling ◽  
Infected Host Cell ◽  
Viral Budding ◽  
Virion Release ◽  
Liquid Ordered

ABSTRACTThe influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will in principle be able to both contribute to curvature induction and sense curvature in order to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered/liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced.SIGNIFICANCE STATEMENTFor influenza virus to release from the infected host cell, controlled viral budding must finalize with membrane scission of the viral envelope. Curiously, influenza carries its own protein, M2, which can sever the membrane of the constricted budding neck. Here we elucidate the physical mechanism of clustering and spatial localization of the M2 scission proteins through a combined computational and experimental approach. Our results provide fundamental insights into how M2 clustering and localization interplays with membrane curvature, membrane lateral stresses, and lipid bilayer phase behavior during viral budding in order to contribute to virion release.

scholarly journals Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding

2018 ◽  
Vol 115 (37) ◽  
pp. E8595-E8603 ◽  
Author(s):  
Jesper J. Madsen ◽  
John M. A. Grime ◽  
Jeremy S. Rossman ◽  
Gregory A. Voth
Keyword(s):  
Host Cell ◽  
Influenza A ◽  
Lipid Membrane ◽  
Transmembrane Protein ◽  
Membrane Curvature ◽  
Coarse Grained ◽  
Membrane Remodeling ◽  
Viral Budding ◽  
Virion Release ◽  
Liquid Ordered

The influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored, and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will, in principle, be able to both contribute to curvature induction and sense curvature to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered–liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced.

3D Reconstruction of Varicella-Zoster Virus Infected Host Cell Nuclei and PML Cages by Serial Section Array-SEM and TEM Tomography.

2012 ◽  
Vol 18 (S2) ◽  
pp. 176-177
Author(s):  
M. Reichelt ◽  
L. Joubert ◽  
J. Perrino ◽  
A. Ko ◽  
I. Phanwar ◽  
...  
Keyword(s):  
3D Reconstruction ◽  
Varicella Zoster Virus ◽  
Host Cell ◽  
Serial Section ◽  
Infected Host ◽  
Cell Nuclei ◽  
Varicella Zoster ◽  
Infected Host Cell ◽  
Sem And Tem

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.

scholarly journals Type II Secretion Substrates ofLegionella pneumophilaTranslocate Out of the Pathogen-Occupied Vacuole via a Semipermeable Membrane

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Hilary K. Truchan ◽  
Harry D. Christman ◽  
Richard C. White ◽  
Nakisha S. Rutledge ◽  
Nicholas P. Cianciotto
Keyword(s):  
Host Cell ◽  
Infected Host ◽  
Type Ii Secretion ◽  
Dependent Manner ◽  
Type Ii ◽  
Murine Macrophages ◽  
Intracellular Infection ◽  
Infected Host Cell ◽  
Cell Cytosol ◽  
Host Cell Cytosol

ABSTRACTLegionella pneumophilareplicates in macrophages in a host-derived phagosome, termed theLegionella-containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p.i.), which is approximately the midpoint of the intracellular life cycle. However, it is detected as early as 6 h p.i. if ProA is hyperexpressed, indicating that translocation depends on the timing of ProA expression and that any other factors necessary for translocation are in place by that time point. Translocation occurs with allL. pneumophilastrains tested and in amoebae, natural hosts forL. pneumophila. It was absent in murine bone marrow-derived macrophages and murine macrophage cell lines. The ChiA chitinase also associated with the cytoplasmic face of the LCVM at 6 h p.i. and in a T2S-dependent manner. Galectin-3 and galectin-8, eukaryotic proteins whose localization is influenced by damage to host membranes, appeared within the LCV of infected human but not murine macrophages beginning at 6 h p.i. Thus, we hypothesize that ProA and ChiA are first secreted into the vacuolar lumen by the activity of the T2S and subsequently traffic into the macrophage cytosol via a novel mechanism that involves a semipermeable LCVM.IMPORTANCEInfection of macrophages and amoebae plays a central role in the pathogenesis ofL. pneumophila, the agent of Legionnaires’ disease. We have previously demonstrated that the T2S system ofL. pneumophilagreatly contributes to intracellular infection. However, the location of T2S substrates within the infected host cell is unknown. This report presents the first evidence of aL. pneumophilaT2S substrate in the host cell cytosol and, therefore, the first evidence of a non-T4S effector trafficking out of the LCV. We also provide the first indication that the LCV is not completely intact but is instead semipermeable and that this occurs in human but not murine macrophages. Given this permeability, we hypothesize that other T2S substrates and LCV lumenal contents can escape into the host cell cytosol. Thus, these substrates may represent a battery of previously unidentified effectors that can interact with host factors and contribute to intracellular infection byL. pneumophila.

scholarly journals Division of the Salmonella-Containing Vacuole and Depletion of Acidic Lysosomes in Salmonella-Infected Host Cells Are Novel Strategies of Salmonella enterica To Avoid Lysosomes

2009 ◽  
Vol 78 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Sandeepa M. Eswarappa ◽  
Vidya Devi Negi ◽  
Sangeeta Chakraborty ◽  
B. K. Chandrasekhar Sagar ◽  
Dipshikha Chakravortty
Keyword(s):  
Infected Cell ◽  
Host Cell ◽  
Salmonella Enterica ◽  
Host Cells ◽  
Infected Host ◽  
Nitrogen Species ◽  
Lysosomal Degradation ◽  
Infected Host Cell

ABSTRACT Salmonella has evolved several strategies to counteract intracellular microbicidal agents like reactive oxygen and nitrogen species. However, it is not yet clear how Salmonella escapes lysosomal degradation. Some studies have demonstrated that Salmonella can inhibit phagolysosomal fusion, whereas other reports have shown that the Salmonella-containing vacuole (SCV) fuses/interacts with lysosomes. Here, we have addressed this issue from a different perspective by investigating if the infected host cell has a sufficient quantity of lysosomes to target Salmonella. Our results suggest that SCVs divide along with Salmonella, resulting in a single bacterium per SCV. As a consequence, the SCV load per cell increases with the division of Salmonella inside the host cell. This demands more investment from the host cell to counteract Salmonella. Interestingly, we observed that Salmonella infection decreases the number of acidic lysosomes inside the host cell both in vitro and in vivo. These events potentially result in a condition in which an infected cell is left with insufficient acidic lysosomes to target the increasing number of SCVs, which favors the survival and proliferation of Salmonella inside the host cell.

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