Glycan receptors of the Polyomaviridae: structure, function, and pathogenesis

O’Hara, Samantha D.; Stehle, Thilo; Garcea, Robert L.

doi:10.1016/j.coviro.2014.05.004

Cited by 28 publications

(26 citation statements)

References 27 publications

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“…The polyomaviruses are small doublestranded DNA (dsDNA) viruses that infect a wide range of hosts, and they bind Sia via the major capsid protein, VP1, which is arranged within the particle as 72 pentamers. The polyomaviruses from humans (JC virus, BK virus, and Merkel Cell polyomavirus) all have a strong preference for Neu5Ac Sia in cell attachment, while viruses from nonhuman primates and other mammalian hosts (simian virus 40) show increased flexibility in Sia recognition as they have a larger, more polar pocket allowing binding to Neu5Gc Sia [46][47][48]. Similarly, rotaviruses, double-stranded RNA (dsRNA) viruses in the Reovirus family, also show a strain-dependent specificity for Neu5Ac or Neu5Gc bindingbovine strain NCDV and porcine strains OSU and CRW-8 have specificity for Neu5Gc while rhesus macaque strain RRV prefers Neu5Ac [49].…”

Section: Neu5gcmentioning

confidence: 99%

Effects of Sialic Acid Modifications on Virus Binding and Infection

Wasik

Barnard

Parrish

2016

Trends in Microbiology

115

118

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Sialic acids (Sias) are abundantly displayed on the surfaces of vertebrate cells, and particularly on all mucosal surfaces. Sias interact with microbes of many types, and are the targets of specific recognition by many different viruses. They may mediate virus binding and infection of cells, or alternatively can act as decoy receptors that bind virions and block virus infection. These nine-carbon backbone monosaccharides naturally occur in many different modified forms, and are attached to underlying glycans through varied linkages, creating significant diversity in the pathogen receptor forms. Here we review the current knowledge regarding the distribution of modified Sias in different vertebrate hosts, tissues, and cells, their effects on viral pathogens where those have been examined, and outline unresolved questions.

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Section: Neu5gcmentioning

confidence: 99%

Effects of Sialic Acid Modifications on Virus Binding and Infection

Wasik

Barnard

Parrish

2016

Trends in Microbiology

115

118

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“…In addition to binding DAF and CAR, a variant of CVB3, CVB3-PD, also binds the proteoglycan heparan sulfate in the absence of CAR or DAF binding (9). Understanding mechanisms of virus-receptor interactions is critically important not only from a basic virology perspective but also because virus-receptor binding has clinical implications, as virus-receptor binding often restricts tissue tropism, affects pathogenesis, contributes to transmission mechanisms, and restricts species specificity (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Polyamine Depletion Abrogates Enterovirus Cellular Attachment

Kicmal

Tate

Dial

et al. 2019

J Virol

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Polyamines are small polycationic molecules with flexible carbon chains that are found in all eukaryotic cells. Polyamines are involved in the regulation of many host processes and have been shown to be implicated in viral replication. Depletion of polyamine pools in cells treated with FDA-approved drugs restricts replication of diverse RNA viruses. Viruses can exploit host polyamines to facilitate nucleic acid packaging, transcription, and translation, but other mechanisms remain largely unknown. Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to the depletion of polyamines and remain a significant public health threat. We employed CVB3 as a model system to investigate a potential proviral role for polyamines using a forward screen. Passaging CVB3 in polyamine-depleted cells generated a mutation in capsid protein VP3 at residue 234. We show that this mutation confers resistance to polyamine depletion. Through attachment assays, we demonstrate that polyamine depletion limits CVB3 attachment to susceptible cells, which is rescued by incubating virus with polyamines. Furthermore, the capsid mutant rescues this inhibition in polyamine-depleted cells. More divergent viruses also exhibited reduced attachment to polyamine-depleted cells, suggesting that polyamines may facilitate attachment of diverse RNA viruses. These studies inform additional mechanisms of action for polyamine-depleting pharmaceuticals, with implications for potential antiviral therapies. IMPORTANCE Enteroviruses are significant human pathogens that can cause severe disease. These viruses rely on polyamines, small positively charged molecules, for robust replication, and polyamine depletion limits infection in vitro and in vivo. The mechanisms by which polyamines enhance enteroviral replication are unknown. Here, we describe how Coxsackievirus B3 (CVB3) utilizes polyamines to attach to susceptible cells and initiate infection. Using a forward genetic screen, we identified a mutation in a receptor-binding amino acid that promotes infection of polyamine-depleted cells. These data suggest that pharmacologically inhibiting polyamine biosynthesis may combat virus infection by preventing virus attachment to susceptible cells.

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“…Studies on HPyV cell tropism have focused on cell-surface entry receptors and co-receptors (Khan et al, 2014;Neu et al, 2013;O'Hara et al, 2014;Pastrana et al, 2013b;Ströh et al, 2014). While the presence of these receptors is essential for infection, cellular factors that bind the HPyV promoter or HPyV regulatory proteins will affect viral transcription and replication and effect viral production (e.g.…”

Section: Introductionmentioning

confidence: 99%

Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines

Moens

Ghelue

Ludvigsen

et al. 2015

Journal of General Virology

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Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines Little is known about cell tropism of the novel HPyVs, and cell cultures allowing virus propagation are lacking. Because viral tropism partially depends on the interaction of cellular transcription factors with the viral promoter, we monitored the promoter activity of all known HPyVs. Therefore, we compared the relative early and late promoter activity of the BK polyomavirus (BKPyV) (WW strain) with the corresponding activities of the other HPyVs in 10 different cell lines derived from brain, colon, kidney, liver, lung, the oral cavity and skin. Our results show that the BKPyV, MCPyV, TSPyV and HPyV12 early promoters displayed the strongest activity in most cell lines tested, while the remaining HPyV had relative low early promoter activity. HPyV12 showed the highest late promoter activity of all HPyVs in most cell lines, but also the BKPyV, MCPyV and TSPyV late promoters belonged to the stronger ones among HPyVs. The HPyVs with weak early promoter activity had in general also weak late promoter activity, except for HPyV10 whose late promoter was relatively strong in six of the 10 cell lines. A 20 bp deletion in the promoter of an HPyV12 variant significantly affected both early and late promoter activity in most cell lines. In conclusion, our findings suggest which cell lines may be suitable for virus propagation and may give an indication of the cell tropism of the HPyVs.

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Glycan receptors of the Polyomaviridae: structure, function, and pathogenesis

Cited by 28 publications

References 27 publications

Effects of Sialic Acid Modifications on Virus Binding and Infection

Effects of Sialic Acid Modifications on Virus Binding and Infection

Polyamine Depletion Abrogates Enterovirus Cellular Attachment

Early and late promoters of BK polyomavirus, Merkel cell polyomavirus, Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines

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