JC Polyomavirus Attachment and Entry: Potential Sites for PML Therapeutics

Mayberry, Colleen L.; Nelson, Christian D. S.; Maginnis, Melissa S.

doi:10.1007/s40588-017-0069-3

Cited by 10 publications

(12 citation statements)

References 116 publications

(200 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…JCPyV is widespread in the human population and largely presents as an asymptomatic kidney and B lymphocyte infection. However, within immunocompromised individuals, such as those previously infected with HIV or undergoing chemotherapy, JCPyV can spread to the CNS and cause PML, a severe demyelinating disease that frequently leads to death (5, 6). In the CNS, JCPyV primarily infects glia, including oligodendrocytes and astrocytes, as well as the cells of the choroid plexus, the latter a critical component of the blood-brain barrier (7).…”

Section: Commentarymentioning

confidence: 99%

Insane in the Membrane: Glial Extracellular Vesicles Transmit Polyomaviruses

Santiana

Altan‐Bonnet

2019

mBio

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are major vehicles for transporting viruses en bloc among hosts. While RNA viruses make up the great majority of transmission by EVs, in a recent article in mBio (mBio 10:e00379-19, 2019, https://mbio.asm.org/content/10/2/e00379-19.long), Morris-Love and colleagues revealed that a double-stranded DNA (dsDNA) virus, JC polyomavirus (JCPyV), a major cause of progressive multifocal leukoencephalopathy (PML), can be released from and transmitted to other glia in EVs. This mode of transmission appears to be highly infectious, independent of the free virus attachment and entry receptors LSTc and 5-HT2, and protected from neutralizing antibodies. This novel form of JCPyV transmission may potentially explain its dissemination into the central nervous system (CNS) and its increased virulence.

show abstract

Section: Commentarymentioning

confidence: 99%

Insane in the Membrane: Glial Extracellular Vesicles Transmit Polyomaviruses

Santiana

Altan‐Bonnet

2019

mBio

View full text Add to dashboard Cite

show abstract

“…In fact, studies have revealed that VP1-specific antibodies from PML patients cannot neutralize VP1 with PML-associated mutations unless subsequent steps in immune reconstitution are taken as well [40, 134]. These recent findings provide an enhanced understanding of JCPyV infection and PML development and suggest that a major area of novel PML therapeutics should focus on humanized mAbs that target PML-associated mutations, vaccines that provide VP1-specific immunity and protect from PML-associated mutation infections, in combination with treatments to boost the host immune system [40, 41, 136].…”

Section: Polyomavirusesmentioning

confidence: 99%

“…Moreover, a broadly-neutralizing antibody that recognizes a highly conserved fusion loop of ZIKV E can neutralize ZIKV in mouse models [243]. Additionally, recent studies to identify a treatment for JCPyV-induced PML demonstrates that the most promising candidates are mAbs that target viral capsid protein VP1 and vaccines that stimulate VP1-based immunity [41]. These treatments likely lead to neutralization of circulating virus and prevent JCPyV binding to receptors on host cells.…”

Section: Perspectivesmentioning

confidence: 99%

Virus–Receptor Interactions: The Key to Cellular Invasion

Maginnis

2018

Journal of Molecular Biology

Self Cite

274

229

View full text Add to dashboard Cite

Virus-receptor interactions play a key regulatory role in viral host range, tissue tropism, and viral pathogenesis. Viruses utilize elegant strategies to attach to one or multiple receptors, overcome the plasma membrane barrier, enter, and access the necessary host cell machinery. The viral attachment protein can be viewed as the "key" that unlocks host cells by interacting with the "lock"-the receptor-on the cell surface, and these lock-and-key interactions are critical for viruses to successfully invade host cells. Many common themes have emerged in virus-receptor utilization within and across virus families demonstrating that viruses often target particular classes of molecules in order to mediate these events. Common viral receptors include sialylated glycans, cell adhesion molecules such as immunoglobulin superfamily members and integrins, and phosphatidylserine receptors. The redundancy in receptor usage suggests that viruses target particular receptors or "common locks" to take advantage of their cellular function and also suggests evolutionary conservation. Due to the importance of initial virus interactions with host cells in viral pathogenesis and the redundancy in viral receptor usage, exploitation of these strategies would be an attractive target for new antiviral therapeutics.

show abstract

“…There lytic infection of glial cells can result in a fatal demyelinating disease termed progressive multifocal leukoencephalopathy (PML) 3 . Currently, there is no licensed vaccine for JCPyV and treatment options are limited and usually seek to address the underlying causes of immunosuppression 4 . Effective antiviral therapies against JCPyV are critical to improve the outcomes of patients suffering from PML.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of JC polyomavirus infectivity by the retrograde transport inhibitor Retro‐2.1

Treasure

Nelson

2020

Microbiology and Immunology

Self Cite

View full text Add to dashboard Cite

JC polyomavirus (JCPyV) is a common human pathogen that results in a chronic asymptomatic infection in healthy adults. Under conditions of immunosuppression, JCPyV spreads to the central nervous system and can cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), a disease for which there are no vaccines or antiviral therapies. Retro-2 is a previously identified small molecule inhibitor that was originally shown to block retrograde transport of toxins such as ricin toxin from endosomes to the Golgi apparatus and endoplasmic reticulum (ER), and Retro-2.1 is a chemical analog of Retro-2 that has been shown to inhibit ricin intoxication of cells at low nanomolar concentrations. Retro-2 has previously been shown to prevent retrograde transport of JCPyV virions to the ER, but the effect of Retro-2.1 on JCPyV infectivity is unknown. Here it is shown that Retro-2.1 inhibits JCPyV with an EC 50 of 3.9 μM. This molecule inhibits JCPyV infection at dosages that are not toxic to human tissue culture cells. Retro-2.1 was also tested against two other polyomaviruses, the human BK polyomavirus and simian virus 40, and was also shown to inhibit infection at similar concentrations. Viral uncoating studies demonstrate that Retro-2.1 inhibits BKPyV infectivity in a manner similar to Retro-2. These studies demonstrate that improved analogs of Retro-2 can inhibit infection at lower dosages than Retro-2 and further optimization of these compounds may lead to effective treatment options for those suffering from JCPyV infection and PML.

show abstract

JC Polyomavirus Attachment and Entry: Potential Sites for PML Therapeutics

Cited by 10 publications

References 116 publications

Insane in the Membrane: Glial Extracellular Vesicles Transmit Polyomaviruses

Insane in the Membrane: Glial Extracellular Vesicles Transmit Polyomaviruses

Virus–Receptor Interactions: The Key to Cellular Invasion

Inhibition of JC polyomavirus infectivity by the retrograde transport inhibitor Retro‐2.1

Contact Info

Product

Resources

About