scholarly journals N-Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

2007 ◽  
Vol 81 (23) ◽  
pp. 12846-12858 ◽  
Author(s):  
Maria A. Campanero-Rhodes ◽  
Alicia Smith ◽  
Wengang Chai ◽  
Sandro Sonnino ◽  
Laura Mauri ◽  
...  
Keyword(s):  
Simian Virus 40 ◽  
High Specificity ◽  
Simian Virus ◽  
Receptor Expression ◽  
Host Cells ◽  
Gm1 Ganglioside ◽  
Ganglioside Gm1 ◽  
Virus Binding ◽  
Host Interactions ◽  
Sv40 Infection

ABSTRACT Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus.

scholarly journals Interaction between Simian Virus 40 Major Capsid Protein VP1 and Cell Surface Ganglioside GM1 Triggers Vacuole Formation

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Yong Luo ◽  
Nasim Motamedi ◽  
Thomas G. Magaldi ◽  
Gretchen V. Gee ◽  
Walter J. Atwood ◽  
...  
Keyword(s):  
Cell Surface ◽  
Capsid Protein ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Host Cells ◽  
Wild Type ◽  
Vacuole Formation ◽  
Cytoplasmic Vacuolization ◽  
Capsid Protein Vp1 ◽  
Sv40 Infection

ABSTRACT Simian virus 40 (SV40), a polyomavirus that has served as an important model to understand many aspects of biology, induces dramatic cytoplasmic vacuolization late during productive infection of monkey host cells. Although this activity led to the discovery of the virus in 1960, the mechanism of vacuolization is still not known. Pentamers of the major SV40 capsid protein VP1 bind to the ganglioside GM1, which serves as the cellular receptor for the virus. In this report, we show that binding of VP1 to cell surface GM1 plays a key role in SV40 infection-induced vacuolization. We previously showed that SV40 VP1 mutants defective for GM1 binding fail to induce vacuolization, even though they replicate efficiently. Here, we show that interfering with GM1-VP1 binding by knockdown of GM1 after infection is established abrogates vacuolization by wild-type SV40. Vacuole formation during permissive infection requires efficient virus release, and conditioned medium harvested late during SV40 infection rapidly induces vacuoles in a VP1- and GM1-dependent fashion. Furthermore, vacuolization can also be induced by a nonreplicating SV40 pseudovirus in a GM1-dependent manner, and a mutation in BK pseudovirus VP1 that generates GM1 binding confers vacuole-inducing activity. Vacuolization can also be triggered by purified pentamers of wild-type SV40 VP1, but not by GM1 binding-defective pentamers or by intracellular expression of VP1. These results demonstrate that SV40 infection-induced vacuolization is caused by the binding of released progeny viruses to GM1, thereby identifying the molecular trigger for the activity that led to the discovery of SV40. IMPORTANCE The DNA tumor virus SV40 was discovered more than a half century ago as a contaminant of poliovirus vaccine stocks, because it caused dramatic cytoplasmic vacuolization of permissive host cells. Although SV40 played a historically important role in the development of molecular and cellular biology, restriction mapping, molecular cloning, and whole-genome sequencing, the basis of this vacuolization phenotype was unknown. Here, we show that SV40-induced vacuolization is triggered by the binding of the major viral capsid protein, VP1, to a cell surface ganglioside receptor, GM1. No other viral proteins or virus replication is required for vacuole formation. Other polyomaviruses utilize different ganglioside receptors, but they do not induce vacuolization. This work identifies the molecular trigger for the phenotype that led to the discovery of this important virus and provides the first molecular insight into an unusual and enigmatic cytopathic effect due to virus infection.

scholarly journals Investigation of the SV40 – Human Cancer Association: Look for the Full Signature of the Virus

2001 ◽  
Vol 17 (3) ◽  
pp. 159-161 ◽  
Author(s):  
Keerti V. Shah ◽  
Dana E. M. Rollison
Keyword(s):  
Risk Factors ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Sensitivity And Specificity ◽  
Human Cancer ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Viral Integration ◽  
Human Community ◽  
Sv40 Infection

In the controversy about the association of simian virus 40 with human cancers, the greatest problem is the ascertainment of SV40 exposure. This difficulty would be resolved if one were to look for all components of SV40 infection. How does SV 40 circulate in the human community? Do cancer patients with SV40-positive tumors have serological correlates of SV 40 infection and of SV40-induced cancer? SV40 association with a cancer should be studied in the context of the known risk factors for that cancer. The tumor cell-virus relationship should be characterized with respect to viral integration and viral localization to the tumor cell. Specimens should be masked and the assays should include panels of specimens to estimate analytic sensitivity and specificity. In view of the rarity of some of the tumors reported to be associated with SV40, a multi-institutional investigation initiated and coordinated by the NIH would be most effective.

African Green Monkey Fibroblast Action Morphology during SV40 Infection

1977 ◽  
Vol 32 (5-6) ◽  
pp. 409-412
Author(s):  
Gerhard Brandner ◽  
Myung-Sam Cho
Keyword(s):  
Tumor Antigen ◽  
Actin Filaments ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
African Green Monkey ◽  
Skin Fibroblasts ◽  
Focus Formation ◽  
Normal Morphology ◽  
Green Monkey ◽  
Sv40 Infection

Abstract Monkey skin fibroblasts were infected with simian virus 40. Cells that exhibited the viral tumor antigen were found to retain the normal morphology of actin filaments up to six days after infection. However when cells were transformed in terms of focus formation they had lost the normal actin morphology.

scholarly journals Pairs of Vp1 Cysteine Residues Essential for Simian Virus 40 Infection

2005 ◽  
Vol 79 (6) ◽  
pp. 3859-3864 ◽  
Author(s):  
Peggy P. Li ◽  
Akira Nakanishi ◽  
Vanessa Fontanes ◽  
Harumi Kasamatsu
Keyword(s):  
Nuclear Localization ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Dominant Negative ◽  
Capsid Proteins ◽  
Cysteine Residues ◽  
Nuclear Trafficking ◽  
Virion Assembly ◽  
Capsid Protein Vp1 ◽  
Sv40 Infection

ABSTRACT Transient disulfide bonding occurs during the intracellular folding and pentamerization of simian virus 40 (SV40) major capsid protein Vp1 (P. P. Li, A. Nakanishi, S. W. Clark, and H. Kasamatsu, Proc. Natl. Acad. Sci. USA 99:1353-1358, 2002). We investigated the requirement for Vp1 cysteine pairs during SV40 infection. Our analysis identified three Vp1 double-cysteine mutant combinations that abolished viability as assayed by plaque formation. Mutating the Cys49-Cys87 pair or the Cys87-Cys254 pair led to ineffective nuclear localization and diminished accumulation of the mutant Vp1s, and the defect extended in a dominant-negative manner to the wild-type minor capsid proteins Vp2/3 and an affinity-tagged recombinant Vp1 expressed in the same cells. Mutating the Cys87-Cys207 pair preserved the nuclear localization and normal accumulation of the capsid proteins but diminished the production of virus-like particles. Our results are consistent with a role for Cys49, Cys87, and Cys254 in the folding and cytoplasmic-nuclear trafficking of Vp1 and with a role for Cys87 and Cys207 in the assembly of infectious particles. These findings suggest that transient disulfide bond formation between certain Vp1 cysteine residues functions at two stages of SV40 infection: during Vp1 folding and oligomerization in the cytoplasm and during virion assembly in the nucleus.

scholarly journals Clathrin- and caveolin-1–independent endocytosis

2005 ◽  
Vol 168 (3) ◽  
pp. 477-488 ◽  
Author(s):  
Eva-Maria Damm ◽  
Lucas Pelkmans ◽  
Jürgen Kartenbeck ◽  
Anna Mezzacasa ◽  
Teymuras Kurzchalia ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Knockout Mouse ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Human Hepatoma ◽  
Wild Type ◽  
Embryonic Fibroblasts ◽  
Caveolin 1

Simian Virus 40 (SV40) has been shown to enter host cells by caveolar endocytosis followed by transport via caveosomes to the endoplasmic reticulum (ER). Using a caveolin-1 (cav-1)–deficient cell line (human hepatoma 7) and embryonic fibroblasts from a cav-1 knockout mouse, we found that in the absence of caveolae, but also in wild-type embryonic fibroblasts, the virus exploits an alternative, cav-1–independent pathway. Internalization was rapid (t1/2 = 20 min) and cholesterol and tyrosine kinase dependent but independent of clathrin, dynamin II, and ARF6. The viruses were internalized in small, tight-fitting vesicles and transported to membrane-bounded, pH-neutral organelles similar to caveosomes but devoid of cav-1 and -2. The viruses were next transferred by microtubule-dependent vesicular transport to the ER, a step that was required for infectivity. Our results revealed the existence of a virus-activated endocytic pathway from the plasma membrane to the ER that involves neither clathrin nor caveolae and that can be activated also in the presence of cav-1.

scholarly journals A Virus-Virus Interaction Circumvents the Virus Receptor Requirement for Infection by Pathogenic Retroviruses

2003 ◽  
Vol 77 (6) ◽  
pp. 3460-3469 ◽  
Author(s):  
David L. Wensel ◽  
Weihua Li ◽  
James M. Cunningham
Keyword(s):  
Cell Surface ◽  
Envelope Glycoprotein ◽  
Gene Activation ◽  
Host Cells ◽  
Virus Binding ◽  
Virus Envelope ◽  
Host Interactions ◽  
Terminal Domain ◽  
Retrovirus Infection ◽  
Ecotropic Virus

ABSTRACT During ongoing C-type retrovirus infection, the probability of leukemia caused by insertional gene activation is markedly increased by the emergence of recombinant retroviruses that repeatedly infect host cells. The murine mink cell focus-inducing (MCF) viruses with this property have acquired characteristic changes in the N-terminal domain of their envelope glycoprotein that specify binding to a different receptor than the parental ecotropic virus. In this report, we show that MCF virus infection occurs through binding to this receptor (termed Syg1) and, remarkably, by a second mechanism that does not utilize the Syg1 receptor. By the latter route, the N-terminal domain of the ecotropic virus glycoprotein expressed on the cell surface in a complex with its receptor activates the fusion mechanism of the MCF virus in trans. The rate of MCF virus spread through a population of permissive human cells was increased by establishment of trans activation, indicating that Syg1 receptor-dependent and -independent pathways function in parallel. Also, trans activation shortened the interval between initial infection and onset of cell-cell fusion associated with repeated infection of the same cell. Our findings indicate that pathogenic retrovirus infection may be initiated by virus binding to cell receptors or to the virus envelope glycoprotein of other viruses expressed on the cell surface. Also, they support a broader principle: that cooperative virus-virus interactions, as well as virus-host interactions, shape the composition and properties of the retrovirus quasispecies.

scholarly journals Patterns of polyadenylation site selection in gene constructs containing multiple polyadenylation signals.

1988 ◽  
Vol 8 (11) ◽  
pp. 4829-4839 ◽  
Author(s):  
R M Denome ◽  
C N Cole
Keyword(s):  
Simian Virus 40 ◽  
Simian Virus ◽  
Polyadenylation Signal ◽  
Coding Region ◽  
S1 Nuclease ◽  
Cytoplasmic Rna ◽  
Sv40 Origin ◽  
Sv40 Infection ◽  
Simplex Virus ◽  
Polyadenylation Signals

We have constructed a series of plasmids containing multiple polyadenylation signals downstream of the herpes simplex virus type 1 (HSV) thymidine kinase (tk)-coding region. The signals used were from the simian virus 40 (SV40) late gene, the HSV tk gene, and an AATAAA-containing segment of the SV40 early region. This last fragment signals polyadenylation poorly in our constructs and not at all during SV40 infection. All plasmids contained the SV40 origin of replication. Plasmids were transfected into Cos-1 cells; after 48 h, cytoplasmic RNA was isolated and the quantity and 3'-end structure of tk mRNAs was analyzed by using S1 nuclease protection assays. In all constructs, all polyadenylation signals were used. Increasing the number of poly(A) signals 3' to the tk-coding region did not affect the total amount of polyadenylated RNA produced, even with the weakest signal. Increasing the distance between two signals caused an increase in the use of the 5' signal and a decrease in the use of the 3' signal. Changing the distance between the 5' cap and first signal did not affect signal use. Analyses of cytoplasmic mRNA stability, nuclear RNA distribution, and transcription in the polyadenylation signal region indicated that the distribution of tk RNAs ending at different poly(A) sites was the result of poly(A) signal choice, not other aspects of RNA metabolism. Four possible mechanisms of polyadenylation signal recognition are discussed.

Identification of the human beta-actin enhancer and its binding factor

1988 ◽  
Vol 8 (1) ◽  
pp. 267-272
Author(s):  
T Kawamoto ◽  
K Makino ◽  
H Niwa ◽  
H Sugiyama ◽  
S Kimura ◽  
...  
Keyword(s):  
Simian Virus 40 ◽  
High Specificity ◽  
Simian Virus ◽  
Mobility Shift ◽  
Beta Actin ◽  
Binding Factor ◽  
Pair Sequence ◽  
Mobility Shift Assay ◽  
Dyad Symmetry

An enhancer of the human beta-actin gene and a factor that specifically interacts with it were detected. A mobility shift assay showed that the factor bound to the 25-base-pair sequence (between +759 and +783 downstream from the cap site) with high specificity. This finding correlated with those of DNase I protection and exonuclease III digestion assays. This binding region of the beta-actin enhancer contained a hyphenated dyad symmetry and an enhancer core-like sequence. In vitro competition experiments indicated that the factor did not bind to the simian virus 40 enhancer core region.

scholarly journals BiP and Multiple DNAJ Molecular Chaperones in the Endoplasmic Reticulum Are Required for Efficient Simian Virus 40 Infection

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Edward C. Goodwin ◽  
Alex Lipovsky ◽  
Takamasa Inoue ◽  
Thomas G. Magaldi ◽  
Anne P. B. Edwards ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Virus Replication ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Model Systems ◽  
Cellular Proteins ◽  
Cellular Genes ◽  
Quality Control Process ◽  
Sv40 Infection ◽  
Capsid Disassembly

ABSTRACT Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infection was specifically inhibited by up to 50-fold by knockdown of four different DNAJ molecular cochaperones or by inhibition of BiP, the Hsp70 partner of DNAJB11. These proteins were not required for the initiation of capsid disassembly, but knockdown markedly inhibited SV40 exit from the ER. In addition, BiP formed a complex with SV40 capsids in the ER in a DNAJB11-dependent fashion. These experiments identify five new cellular proteins required for SV40 infection and suggest that the binding of BiP to the capsid is required for ER exit. Further studies of these proteins will provide insight into the molecular mechanisms of polyomavirus infection and ER function. IMPORTANCE The polyomaviruses, including simian virus 40 (SV40), are important human pathogens and model systems for exploring the general features of virus replication and cell biology. We used a genetic system to interrogate the role of cellular genes in SV40 infection. Based on the results of this unbiased genetic screen and analysis of proteins related to the strongest hit from the screen, we identified five new cellular proteins required for the entry of SV40 into cells. These proteins physically associate with SV40 in the endoplasmic reticulum (ER) during virus entry and are required for exit of the partially disassembled virus from this organelle. These results demonstrate that the polyomaviruses have coopted an ER-localized protein quality control process to initiate disassembly and transit through the cell on their way to the nuclear site of virus replication.

scholarly journals Inhibitors of COP-mediated Transport and Cholera Toxin Action Inhibit Simian Virus 40 Infection

2002 ◽  
Vol 13 (5) ◽  
pp. 1750-1764 ◽  
Author(s):  
Ayanthi A. Richards ◽  
Espen Stang ◽  
Rainer Pepperkok ◽  
Robert G. Parton
Keyword(s):  
Endoplasmic Reticulum ◽  
Cholera Toxin ◽  
Brefeldin A ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Potent Inhibition ◽  
Successful Infection ◽  
Sv40 Infection ◽  
Dependent Transport ◽  
Infectious Entry

Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from surface caveolae to the endoplasmic reticulum in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A and by incubation at 20°C. Subsequent to the entry step, the virus reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This intracellular trafficking pathway is also brefeldin A sensitive. Infection is strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1 (Arf1) and Sar1 mutants and by microinjection of antibodies to βCOP. In addition, we demonstrate a potent inhibition of SV40 infection by the dipeptideN-benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI- and COPII-dependent transport steps for successful infection.

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