Involvement of gangliosides in the interaction between BK virus and Vero cells

Sinibaldi, L.; Goldoni, Paola; Pietropaolo, Valeria; Longhi, Catia; Orsi, N

doi:10.1007/bf01316682

Cited by 30 publications

(48 citation statements)

References 18 publications

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“…Early receptor studies elucidated a role for sialic acids and polysialylated gangliosides in BKV infectious entry into Vero cells and in virus binding to red blood cells (35,40,41). The linkage of sialic acid and the potential role of glycoproteins in infection were not elucidated in these early studies.…”

mentioning

confidence: 99%

An N-Linked Glycoprotein with α(2,3)-Linked Sialic Acid Is a Receptor for BK Virus

Dugan

Eash

Atwood

2005

J Virol

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mentioning

confidence: 99%

An N-Linked Glycoprotein with α(2,3)-Linked Sialic Acid Is a Receptor for BK Virus

Dugan

Eash

Atwood

2005

J Virol

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“…Other studies have also shown that the addition of soluble gangliosides attenuates BKV-mediated hemagglutination (45). Treatment of Vero cells with neuraminidase, which cleaves sialic acid residues in the sugar moiety contained in many gangliosides and glycoproteins, inhibits BKV infection, and the addition of a mixture of Vero cell gangliosides to these treated cells restores infection (44). Gangliosides have been identified as receptors for the polyomaviruses SV40 and Py, both of which also enter the cell via a caveola-dependent mechanism (19,49).…”

mentioning

confidence: 99%

Identification of Gangliosides GD1b and GT1b as Receptors for BK Virus

Low¹,

Magnuson

Tsai

et al. 2006

J Virol

169

155

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Gangliosides have been shown to be plasma membrane receptors for both murine polyomavirus and SV40, while JC virus uses serotonin receptors. In contrast, little is known of the membrane receptor and entry pathway for BK virus (BKV), which can cause severe disease in immunosuppressed bone marrow and renal transplant patients. Using sucrose flotation assays, we investigated BKV binding to and interaction with human erythrocyte membranes and determined that this interaction was dependent on a neuraminidase-sensitive, proteinase K-resistant molecule. BKV was found to interact with the gangliosides GT1b and GD1b. The terminal ␣2-8-linked disialic acid motif, present in both of these gangliosides, is likely to be important for this interaction. We also determined that the addition of GD1b and GT1b to LNCaP cells, which are normally resistant to BKV infection, made them susceptible to the virus. In addition, BKV interacted with membranes extracted from the endoplasmic reticulum (ER) and infection was blocked by the addition of brefeldin A, which interferes with transport from the ER to the Golgi apparatus. These data demonstrate that BKV uses the gangliosides GT1b and GD1b as receptors and passes through the ER on the way to the nucleus.

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“…Though the exact identity of the BK receptor(s) is unknown, evidence suggests that gangliosides type II, GD1a, and GT play important roles in the initial interaction between BKV and the permissive monkey kidney (Vero) cell line, as well as in BKV hemagglutination of human type O red blood cells (54,59,60). Following penetration of the target cell membrane and BKV internalization, the viral genome is delivered to the host cell nucleus.…”

mentioning

confidence: 99%

Infection of Vero Cells by BK Virus Is Dependent on Caveolae

Eash

Querbes

Atwood

2004

J Virol

133

145

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Polyomavirus-associated nephropathy occurs in ϳ5% of renal transplant recipients and results in loss of graft function in 50 to 70% of these patients. The disease is caused by reactivation of the common human polyomavirus BK (BKV) in the transplanted kidney. The early events in productive BKV infection are unknown. In this report, we focus on elucidating the mechanisms of BKV internalization in its target cell. Our data reveal that BKV entry into permissive Vero cells is slow, is independent of clathrin-coated-pit assembly, is dependent on an intact caveolin-1 scaffolding domain, is sensitive to tyrosine kinase inhibition, and requires cholesterol. BKV colocalizes with the caveola-mediated endocytic marker cholera toxin subunit B but not with the clathrin-dependent endocytic marker transferrin. In addition, BKV infectious entry is sensitive to elevation in intracellular pH. These findings indicate that BKV entry into Vero cells occurs by caveola-mediated endocytosis involving a pH-dependent step.Humans are the natural host species for two members of the polyomavirus family, BK virus (BKV) and JC virus (JCV) (22). Both viruses establish persistent subclinical infections in the kidneys and peripheral blood in 85% of the population worldwide (10, 36). The urotheliotropic nature of BKV is characterized by infection of the epithelial lining of the collective ducts, the transitional epithelial cells of the renal calyces, the parietal epithelium of the Bowman's capsule, and the transitional epithelium of the renal pelvis and the urinary tract (11, 56). Sporadic reactivation of BKV resulting in limited viral replication is seen in 0.5 to 20% of healthy seropositive individuals, yet renal function is left unaffected (20,23,62). A dramatic increase in viral activity leading to disease progression occurs predominantly in the context of greatly impaired T-cell-mediated immunity (26,27).Kidney transplant recipients are subjected to a potent immunosuppressive therapy and are thus at a high risk for exacerbated BKV replication (1). Active BKV infection in the renal allograft, known as polyomavirus nephropathy, has been linked to progressive graft dysfunction and ultimate graft loss (13). Sustained high levels of viral replication result in lytic destruction of the host tubular cells and release of BKV progeny to perpetuate the infection (1, 33, 34). BKV, the causative agent of polyomavirus nephropathy, is drawing increasing attention as a significant factor in the failure of renal transplants (48).Similar to those of the other polyomaviruses, BK virions are small (40.5 to 45 nm in diameter) and consist of a superhelical circular double-stranded DNA genome contained within a nonenveloped icosahedral capsid (18). Though the exact identity of the BK receptor(s) is unknown, evidence suggests that gangliosides type II, GD1a, and GT play important roles in the initial interaction between BKV and the permissive monkey kidney (Vero) cell line, as well as in BKV hemagglutination of human type O red blood cells (54,59,60). Following pen...

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Involvement of gangliosides in the interaction between BK virus and Vero cells

Abstract: BK virus infectivity was inhibited by gangliosides extracted from Vero cells and by standard preparations of different gangliosides. Gangliosides were also able to restore the susceptibility of glycosidase-treated Vero cells to BK virus infection.

Cited by 30 publications

References 18 publications

An N-Linked Glycoprotein with α(2,3)-Linked Sialic Acid Is a Receptor for BK Virus

An N-Linked Glycoprotein with α(2,3)-Linked Sialic Acid Is a Receptor for BK Virus

Identification of Gangliosides GD1b and GT1b as Receptors for BK Virus

Infection of Vero Cells by BK Virus Is Dependent on Caveolae

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