Effects of DEAE-dextran on infection and hemolysis by VSV. Evidence that nonspecific electrostatic interactions mediate effective binding of VSV to cells

Bailey, Carole A.; Miller, Douglas K.; Lenard, John

doi:10.1016/0042-6822(84)90429-x

Cited by 48 publications

(38 citation statements)

References 16 publications

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“…This is supported by the observation that the activity of the extracted proteins was unaffected after heating or trypsin digestion (Table 5). This result is in agreement with the previously reported effect of trypsin treatment of goose (Seganti et al, 1982) or human erythrocytes (Bailey et al, 1984), which produced an enhancement of VSV binding and He.…”

Section: Discussionsupporting

confidence: 83%

“…This suggests that binding of VSV to the cell membrane involves (i) an electrostatic interaction between positive amino acid sequences of viral G envelope glycoprotein and an anionic group on the cell membrane and (ii) a tight hydrophobic linkage between a lipophilic peptide segment of G glycoprotein and a lipid portion of the receptor on the membrane. Bailey et al (1984) have suggested that electrostatic interactions can mediate VSV binding to the cell surface. It was shown that the poly-cation DEAE-dextran increased the binding of VSV to BHK-21 cells and erythrocytes of several species; He was equally enhanced.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Membrane Components of the Erythrocyte Involved in Vesicular Stomatitis Virus Attachment and Fusion at Acidic pH

Mastromarino

Conti

Goldoni

et al. 1987

Journal of General Virology

130

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SUMMARYGoose erythrocyte membranes were isolated and tested for their ability to compete with red cell receptors for vesicular stomatitis virus (VSV) attachment and fusion at acidic pH. Crude membranes, solubilized with Triton X-100, Tween 80 and octyl-/~-Dglucopyranoside, showed a dose-dependent inhibitory effect on virus binding and haemolysis. The chemical nature of the active molecules was investigated by enzyme digestion and by separation of purified components. Only the lipid moiety, specifically phospholipid and glycolipid, was found to inhibit VSV attachment; a more detailed analysis of these molecules showed that phosphatidylinositol, phosphatidylserine and GM3 ganglioside were responsible for the inhibitory activity and could therefore represent VSV binding sites on goose erythrocyte membranes. Removal of negatively charged groups from these molecules by enzymic treatment significantly reduced their activity, suggesting that electrostatic interactions play an important role in the binding of VSV to the cell surface. Enzymic digestion of whole erythrocytes confirmed the involvement of membrane lipid molecules in the cell surface receptor for VSV.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Characterization of Membrane Components of the Erythrocyte Involved in Vesicular Stomatitis Virus Attachment and Fusion at Acidic pH

Mastromarino

Conti

Goldoni

et al. 1987

Journal of General Virology

130

View full text Add to dashboard Cite

show abstract

“…VSV with its own G protein has a very broad host range, including insects, mammals, and fish (7). Our current understanding of the VSV entry process is that association with the cell likely occurs through electrostatic interactions (46,47). Whether a specific receptor is engaged in the entry process remains uncertain, but the broad host range suggests a well-conserved molecule or the use of multiple receptors.…”

Section: Discussionmentioning

confidence: 99%

Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors

Beier

Saunders

Oldenburg

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

164

198

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To understand how the nervous system processes information, a map of the connections among neurons would be of great benefit. Here we describe the use of vesicular stomatitis virus (VSV) for tracing neuronal connections in vivo. We made VSV vectors that used glycoprotein (G) genes from several other viruses. The G protein from lymphocytic choriomeningitis virus endowed VSV with the ability to spread transsynaptically, specifically in an anterograde direction, whereas the rabies virus glycoprotein gave a specifically retrograde transsynaptic pattern. The use of an avian G protein fusion allowed specific targeting of cells expressing an avian receptor, which allowed a demonstration of monosynaptic anterograde tracing from defined cells. Synaptic connectivity of pairs of virally labeled cells was demonstrated by using slice cultures and electrophysiology. In vivo infections of several areas in the mouse brain led to the predicted patterns of spread for anterograde or retrograde tracers.

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“…While LDLR has been suggested to be one of the receptors for VSV (16), previous studies also suggested that phosphatidylserine (17)(18)(19), sialoglycolipids (20), heparan sulfate (21), and virus-cell membrane electrostatic interactions (56,57) may play an important role in VSV attachment. We employed a cell surface "shaving" technique with trypsin to remove surface LDLR, and our data showed that VSV can indeed attach to PDAC cells independently of LDLR.…”

Section: Figmentioning

confidence: 99%

“…While future studies are needed to identify specific defects of LDLR in LDL uptake and VSV attachment, here we decided to use an alternative approach to improve VSV attachment by targeting LDLR-independent VSV attachment. Previous studies suggested that phosphatidylserine (17)(18)(19), sialoglycolipids (20), heparan sulfate (21), or electrostatic interactions between VSV and the cell membrane (56,57) could play an important role in VSV attachment. As none of those studies examined PDAC cell lines, we wanted to confirm that LDLR-independent attachment also occurs in PDAC cell lines.…”

Section: Vsv Attachment To Hpaf-ii Cells Is Impairedmentioning

confidence: 99%

Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus

Felt

Droby

Grdzelishvili

2017

J Virol

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Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma cell (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of resistance are still unclear. JAK1/2 inhibitors (such as ruxolitinib and JAK inhibitor I) strongly stimulate VSV replication and oncolysis in all resistant cell lines but only partially improve the susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication rather than on receptor specificity, with several ubiquitously expressed cell surface molecules playing a role in VSV attachment to host cells. However, as VSV attachment to PDAC cells has never been tested before, here we examined if it was possibly inhibited in resistant PDAC cells. Our data show a dramatically weaker attachment of VSV to HPAF-II cells, the most resistant human PDAC cell line. Although sequence analysis of low-density lipoprotein (LDL) receptor (LDLR) mRNA did not reveal any amino acid substitutions in this cell line, HPAF-II cells displayed the lowest level of LDLR expression and dramatically lower LDL uptake. Treatment of cells with various statins strongly increased LDLR expression levels but did not improve VSV attachment or LDL uptake in HPAF-II cells. However, LDLR-independent attachment of VSV to HPAF-II cells was dramatically improved by treating cells with Polybrene or DEAE-dextran. Moreover, combining VSV with ruxolitinib and Polybrene or DEAE-dextran successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication.IMPORTANCE Oncolytic virus (OV) therapy is an anticancer approach that uses viruses that selectively infect and kill cancer cells. This study focuses on oncolytic vesicular stomatitis virus (VSV) against pancreatic ductal adenocarcinoma (PDAC) cells. Although VSV is effective against most PDAC cells, some are highly resistant to VSV, and the mechanisms are still unclear. Here we examined if VSV attachment to cells was inhibited in resistant PDAC cells. Our data show very inefficient attachment of VSV to the most resistant human PDAC cell line, HPAF-II. However, VSV attachment to HPAF-II cells was dramatically improved by treating cells with polycations. Moreover, combining VSV with polycations and ruxolitinib (which inhibits antiviral signaling) successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication. We envision that this novel triple-combination approach could be used in the future to treat PDAC tumors that are highly resistant to OV therapy.KEYWORDS DEAE-dextran, combination treatment, oncolytic virus, pancreatic cancer, Polybrene, polycation, resistance, vesicular stomatitis virus, virus attachment, type I interferon, ruxolitinib

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Effects of DEAE-dextran on infection and hemolysis by VSV. Evidence that nonspecific electrostatic interactions mediate effective binding of VSV to cells

Cited by 48 publications

References 16 publications

Characterization of Membrane Components of the Erythrocyte Involved in Vesicular Stomatitis Virus Attachment and Fusion at Acidic pH

Characterization of Membrane Components of the Erythrocyte Involved in Vesicular Stomatitis Virus Attachment and Fusion at Acidic pH

Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors

Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus

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