scholarly journals An unusual trafficking domain in MSRP6 defines a complex needed for Maurer’s clefts anchoring and maintenance in P. falciparum infected red blood cells

2021 ◽  
Author(s):  
Alexandra Blancke Soares ◽  
Jan Stäcker ◽  
Svenja Schwald ◽  
Wieteke Hoijmakers ◽  
Nahla Galal Metwally ◽  
...  
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Virulence Factor ◽  
Structural Integrity ◽  
Surface Display ◽  
Parasite Survival ◽  
Cell Remodeling ◽  
Infected Rbcs ◽  
Host Cell Surface ◽  
Maurer's Clefts

AbstractIntracellular malaria blood stage parasites remodel their host cell, a process essential for parasite survival and a cause of pathology in malaria infections. Host cell remodeling depends on the export of different classes of exported parasite proteins into the infected red blood cell (RBC). Here we show that members of a recently discovered group of difficult to predict exported proteins harbor an N-terminal export domain, similar to other classes of exported proteins, indicating that this is a common theme among all classes of exported proteins. For one such protein, MSRP6 (MSP-7 related protein 6), we identified a second, untypical export-mediating domain that corresponded to its MSP7-like region. In addition to its function in export, this domain also mediated attachment to the Maurer’s clefts, prominent parasite-induced structures in the host cell where MSRP6 is located. Using BioID with the Maurer’s clefts attachment domain of MSRP6 to identify interactors and compartment neighbors in live parasites we discovered a novel complex of proteins at the Maurer’s clefts. We show that this complex is necessary for the anchoring and maintaining the structural integrity of the Maurer’s clefts. The Maurer’s clefts are believed to be involved in the transport of the major virulence factor PfEMP1 to the host cell surface where it mediates cytoadherence of infected RBCs to endothelial cells, a main reason for the importance of host cell modifications for parasite virulence in the human host. Taking advantage of MSRP6 complex mutants and IT4 parasites that we modified to express only one specific PfEMP1 we find that abolishing Maurer’s clefts anchoring was neither needed for PfEMP1 transport to the host cell surface nor for cytoadherence. Altogether, this work reveals parasite proteins involved in Maurer’s clefts anchoring and maintenance and unexpectedly finds that these functions are dispensable for virulence factor transport and surface display.

scholarly journals A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and comigrates to knobs on the host cell surface

2014 ◽  
Vol 28 (10) ◽  
pp. 4420-4433 ◽  
Author(s):  
Alexander Oberli ◽  
Leanne M. Slater ◽  
Erin Cutts ◽  
Françoise Brand ◽  
Esther Mundwiler‐Pachlatko ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Surface ◽  
Host Cell ◽  
Virulence Factor ◽  
Host Cell Surface

scholarly journals A Single-Pass Type I Membrane Protein from the Apicomplexan Parasite Cryptosporidium parvum with Nanomolar Binding Affinity to Host Cell Surface

2021 ◽  
Vol 9 (5) ◽  
pp. 1015
Author(s):  
Tianyu Zhang ◽  
Xin Gao ◽  
Dongqiang Wang ◽  
Jixue Zhao ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Cell Surface ◽  
Host Cell ◽  
Binding Affinity ◽  
Cryptosporidium Parvum ◽  
Host Cells ◽  
Watery Diarrhea ◽  
Type I ◽  
Single Pass ◽  
Host Cell Surface

Cryptosporidium parvum is a globally recognized zoonotic parasite of medical and veterinary importance. This parasite mainly infects intestinal epithelial cells and causes mild to severe watery diarrhea that could be deadly in patients with weakened or defect immunity. However, its molecular interactions with hosts and pathogenesis, an important part in adaptation of parasitic lifestyle, remain poorly understood. Here we report the identification and characterization of a C. parvum T-cell immunomodulatory protein homolog (CpTIPH). CpTIPH is a 901-aa single-pass type I membrane protein encoded by cgd5_830 gene that also contains a short Vibrio, Colwellia, Bradyrhizobium and Shewanella (VCBS) repeat and relatively long integrin alpha (ITGA) N-terminus domain. Immunofluorescence assay confirmed the location of CpTIPH on the cell surface of C. parvum sporozoites. In congruence with the presence of VCBS repeat and ITGA domain, CpTIPH displayed high, nanomolar binding affinity to host cell surface (i.e., Kd(App) at 16.2 to 44.7 nM on fixed HCT-8 and CHO-K1 cells, respectively). The involvement of CpTIPH in the parasite invasion is partly supported by experiments showing that an anti-CpTIPH antibody could partially block the invasion of C. parvum sporozoites into host cells. These observations provide a strong basis for further investigation of the roles of CpTIPH in parasite-host cell interactions.

scholarly journals Extracellular Bacterial Pathogen Induces Host Cell Surface Reorganization to Resist Shear Stress

2009 ◽  
Vol 5 (2) ◽  
pp. e1000314 ◽  
Author(s):  
Guillain Mikaty ◽  
Magali Soyer ◽  
Emilie Mairey ◽  
Nelly Henry ◽  
Dave Dyer ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cell Surface ◽  
Host Cell ◽  
Bacterial Pathogen ◽  
Host Cell Surface

scholarly journals Heparan Sulfate Facilitates Spike Protein-Mediated SARS-CoV-2 Host Cell Invasion and Contributes to Increased Infection of SARS-CoV-2 G614 Mutant and in Lung Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jingwen Yue ◽  
Weihua Jin ◽  
Hua Yang ◽  
John Faulkner ◽  
Xuehong Song ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Host Cell ◽  
Host Cells ◽  
Cell Surface Receptor ◽  
Spike Protein ◽  
Effective Prevention ◽  
Heparin Derivatives ◽  
Host Cell Surface

The severe acute respiratory syndrome (SARS)-like coronavirus disease (COVID-19) is caused by SARS-CoV-2 and has been a serious threat to global public health with limited treatment. Cellular heparan sulfate (HS) has been found to bind SARS-CoV-2 spike protein (SV2-S) and co-operate with cell surface receptor angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 infection of host cells. In this study, we determined that host cell surface SV2-S binding depends on and correlates with host cell surface HS expression. This binding is required for SARS-Cov-2 virus to infect host cells and can be blocked by heparin lyase, HS antagonist surfen, heparin, and heparin derivatives. The binding of heparin/HS to SV2-S is mainly determined by its overall sulfation with potential, minor contribution of specific SV2-S binding motifs. The higher binding affinity of SV2-S G614 mutant to heparin and upregulated HS expression may be one of the mechanisms underlying the higher infectivity of the SARS-CoV-2 G614 variant and the high vulnerability of lung cancer patients to SARS-CoV-2 infection, respectively. The higher host cell infection by SARS-CoV-2 G614 variant pseudovirus and the increased infection caused by upregulated HS expression both can be effectively blocked by heparin lyase and heparin, and possibly surfen and heparin derivatives too. Our findings support blocking HS-SV2-S interaction may provide one addition to achieve effective prevention and/treatment of COVID-19.

scholarly journals Significance of thiol-disulfide balance in SARS-CoV-2 infection

2021 ◽  
Vol 72 (3) ◽  
pp. 30-36
Author(s):  
Tatjana Simić
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Protein Interactions ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Alkylating Agents ◽  
Protein S ◽  
Protein Protein Interactions ◽  
Virus Surface ◽  
Host Cell Surface

Studies of the molecular mechanisms regarding interaction of different viruses with receptors on the host cell surface have shown that the viral entry depends on the specific relationship between free thiol (SH) groups and disulfides on the virus surface, as well as the thiol disulfide balance on the host cell surface. The presence of oxidizing compounds or alkylating agents, which disturb the thiol-disulfide balance on the surface of the virus, can also affect its infectious potential. Disturbed thiol-disulfide balance may also influence protein-protein interactions between SARS-CoV-2 protein S and ACE2 receptors of the host cell. This review presents the basic mechanisms of maintaining intracellular and extracellular thiol disulfide balance and previous experimental and clinical evidence in favor of impaired balance in SARS-CoV-2 infection. Besides, the results of the clinical application or experimental analysis of compounds that induce changes in the thiol disulfide balance towards reduction of disulfide bridges in proteins of interest in COVID-19 infection are presented.

Brilacidin, a COVID-19 Drug Candidate, demonstrates broad-spectrum antiviral activity against human coronaviruses OC43, 229E and NL63 through targeting both the virus and the host cell

2021 ◽  
Author(s):  
Yanmei Hu ◽  
Hyunil Jo ◽  
William DeGrado ◽  
Jun Wang
Keyword(s):  
Antiviral Activity ◽  
Cell Surface ◽  
Host Cell ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Drug Candidate ◽  
Host Defense Peptides ◽  
Antibiotic Drug ◽  
Host Cell Surface ◽  
Human Coronaviruses

Brilacidin, a mimetic of host defense peptides (HDPs), is currently in phase 2 clinical trial as an antibiotic drug candidate. A recent study reported that brilacidin has antiviral activity against SARS-CoV-2 by inactivating the virus. In this work, we discovered an additional mechanism of action of brilacidin by targeting heparan sulfate proteoglycans (HSPGs) on host cell surface. Brilacidin, but not acetyl brilacidin, inhibits the entry of SARS-CoV-2 pseudovirus into multiple cell lines, and heparin, a HSPG mimetic, abolishes the inhibitory activity of brilacidin on SARS-CoV-2 pseudovirus cell entry. In addition, we found that brilacidin has broad-spectrum antiviral activity against multiple human coronaviruses (HCoVs) including HCoV-229E, HCoV-OC43, and HCoV-NL63. Mechanistic studies revealed that brilacidin has a dual antiviral mechanism of action including virucidal activity and binding to coronavirus attachment factor HSPGs on host cell surface. Brilacidin partially loses its antiviral activity when heparin was included in the cell cultures, supporting the host-targeting mechanism. Drug combination therapy showed that brilacidin has a strong synergistic effect with remdesivir against HCoV-OC43 in cell culture. Taken together, this study provides appealing findings for the translational potential of brilacidin as a broad-spectrum antiviral for coronaviruses including SARS-CoV-2.

scholarly journals Probability of Immobilization on Host Cell Surface Regulates Viral Infectivity

2020 ◽  
Vol 125 (12) ◽  
Author(s):  
Michael C. DeSantis ◽  
Chunjuan Tian ◽  
Jin H. Kim ◽  
Jamie L. Austin ◽  
Wei Cheng
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Viral Infectivity ◽  
Host Cell Surface

Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection

2015 ◽  
Vol 47 (1) ◽  
pp. 34-45 ◽  
Author(s):  
Petros Kingstone Chigwechokha ◽  
Mutsumi Tabata ◽  
Sayaka Shinyoshi ◽  
Kazuki Oishi ◽  
Kyosuke Araki ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Host Cell ◽  
Edwardsiella Tarda ◽  
Host Cell Surface

scholarly journals Interaction of Chlamydia trachomatis with Mammalian Cells Is Independent of Host Cell Surface Heparan Sulfate Glycosaminoglycans

2006 ◽  
Vol 74 (3) ◽  
pp. 1795-1799 ◽  
Author(s):  
Richard S. Stephens ◽  
Jesse M. Poteralski ◽  
Lynn Olinger
Keyword(s):  
Chlamydia Trachomatis ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Host Cell ◽  
Cell Line ◽  
Mammalian Cells ◽  
Chlamydial Infection ◽  
Functional Role ◽  
A Cell ◽  
Host Cell Surface

ABSTRACT The hypothesis that host cell surface heparan sulfate is required to promote chlamydial infection was tested using a cell line (CHO-18.4) containing a single retroviral insertion and the concomitant loss of heparan sulfate biosynthesis. Tests of chlamydial infectivity of heparan sulfate-deficient CHO-18.4 cells and parental cells, CHO-22, demonstrated that both were equally sensitive to infection by Chlamydia trachomatis serovars L2 and D. These data do not support the hypothesis and demonstrate that host cell surface heparan sulfate does not serve an essential functional role in chlamydial infectivity.

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