Re-analysis of SARS-CoV-2-infected host cell proteomics time-course data by impact pathway analysis and network analysis: a potential link with inflammatory response

AbstractThe disease known as coronavirus disease 19 (COVID-19), potentially caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has hit the world hard, and has led to an unprecedent health and economic crisis. In order to develop treatment options able to stop or ameliorate SARS-CoV-2 effects, we need to understand the biology of the virus inside cells, but this kind of studies are still scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. In the present study, we use the publicly available proteomics data from this study to re-analyze the mechanisms altered by the virus infection by impact pathways analysis and network analysis. Proteins linked to inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be regulated. The up-regulation of the inflammatory-related proteins observed could be linked to the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients.

Macrophage Activation Redirects Yersinia-Infected Host Cell Death from Apoptosis to Caspase-1-Dependent Pyroptosis

PLoS Pathogens ◽

10.1371/journal.ppat.0030161 ◽

2007 ◽

Vol 3 (11) ◽

pp. e161 ◽

Cited By ~ 133

Author(s):

Tessa Bergsbaken ◽

Brad T Cookson

Keyword(s):

Cell Death ◽

Host Cell ◽

Macrophage Activation ◽

Infected Host ◽

Infected Host Cell ◽

Caspase 1 ◽

Host Cell Death

Transbilayer phospholipid asymmetry in Plasmodium knowlesi-infected host cell membrane

Science ◽

10.1126/science.7233198 ◽

1981 ◽

Vol 212 (4498) ◽

pp. 1047-1049 ◽

Cited By ~ 51

Author(s):

C. Gupta ◽

G. Mishra

Keyword(s):

Cell Membrane ◽

Host Cell ◽

Plasmodium Knowlesi ◽

Infected Host ◽

Host Cell Membrane ◽

Infected Host Cell ◽

Phospholipid Asymmetry

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

10.1101/291120 ◽

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.

Recombinant single chain antibodies as an instrument to search proteins involved in the interaction of microsporidia and other intracellular parasites with an infected host cell

Protistology ◽

10.21685/1680-0826-2019-13-1-1 ◽

2019 ◽

Vol 13 (1) ◽

Author(s):

Alexander A. Tsarev ◽

◽

Igorj V Senderskiy ◽

Sergei A. Timofeev ◽

Vladimir S. Zhuravlyov ◽

...

Keyword(s):

Host Cell ◽

Infected Host ◽

Single Chain ◽

Single Chain Antibodies ◽

Infected Host Cell ◽

Intracellular Parasites

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

Microscopy and Microanalysis ◽

10.1017/s1431927612002735 ◽

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.

Attenuated cytomegalovirus capable of cellular infection containing a foreign gene capable of expression in a cytomegalovirus-infected host cell; potential vaccine

Vaccine ◽

10.1016/0264-410x(89)90058-3 ◽

1989 ◽

Vol 7 (2) ◽

pp. 161

Keyword(s):

Host Cell ◽

Infected Host ◽

Foreign Gene ◽

Cell Potential ◽

Infected Host Cell ◽

Potential Vaccine

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

mBio ◽

10.1128/mbio.00870-17 ◽

2017 ◽

Vol 8 (3) ◽

Cited By ~ 16

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.

Association of newly synthesized major fl coat protein with infected host cell inner membrane

Journal of Supramolecular Structure ◽

10.1002/jss.400010103 ◽

1972 ◽

Vol 1 (1) ◽

pp. 8-18 ◽

Cited By ~ 62

Author(s):

Henry Smilowitz ◽

John Carson ◽

Phillips W. Robbins

Keyword(s):

Coat Protein ◽

Host Cell ◽

Infected Host ◽

Inner Membrane ◽

Infected Host Cell

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

Infection and Immunity ◽

10.1128/iai.00668-09 ◽

2009 ◽

Vol 78 (1) ◽

pp. 68-79 ◽

Cited By ~ 28

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.