Pathogenesis of human cytomegalovirus in the immunocompromised host

Griffiths, Paul; Reeves, Matthew B.

doi:10.1038/s41579-021-00582-z

Cited by 363 publications

(331 citation statements)

References 155 publications

(173 reference statements)

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“…HCMV is a member of the Herpesviridae family, which are enveloped viruses containing double-stranded DNA [102]. HCMV infects more than 90% of local populations depending on socio-economic status [103]. Infection typically is asymptomatic in healthy individuals but causes significant morbidity and death in immunocompromised individuals and newborns [103].…”

Section: Viral Genome Replication and P97mentioning

confidence: 99%

How Viruses Use the VCP/p97 ATPase Molecular Machine

Das

Dudley

2021

Viruses

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Viruses are obligate intracellular parasites that are dependent on host factors for their replication. One such host protein, p97 or the valosin-containing protein (VCP), is a highly conserved AAA ATPase that facilitates replication of diverse RNA- and DNA-containing viruses. The wide range of cellular functions attributed to this ATPase is consistent with its participation in multiple steps of the virus life cycle from entry and uncoating to viral egress. Studies of VCP/p97 interactions with viruses will provide important information about host processes and cell biology, but also viral strategies that take advantage of these host functions. The critical role of p97 in viral replication might be exploited as a target for development of pan-antiviral drugs that exceed the capability of virus-specific vaccines or therapeutics.

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Section: Viral Genome Replication and P97mentioning

confidence: 99%

How Viruses Use the VCP/p97 ATPase Molecular Machine

Das

Dudley

2021

Viruses

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“…HCMV is a member of the Herpesviridae family, which are enveloped viruses containing double-stranded DNA [99]. HCMV infects more than 90% of local populations depending on socio-economic status [100]. Infection typically is asymptomatic in healthy individuals, but causes significant morbidity and death in immunocompromised individuals and newborns [100].…”

Section: Viral Genome Replication and P97mentioning

confidence: 99%

“…HCMV infects more than 90% of local populations depending on socio-economic status [100]. Infection typically is asymptomatic in healthy individuals, but causes significant morbidity and death in immunocompromised individuals and newborns [100]. Using a focused siRNA screen directed against 160 membrane-associated factors, Lin et al showed that knockdown of VCP had the greatest negative effect on a recombinant HCMV expressing GFP [29].…”

Section: Viral Genome Replication and P97mentioning

confidence: 99%

How Viruses Use the VCP/p97 ATPase Molecular Machine

Das¹,

Dudley²

2021

Preprint

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“…While the decoy receptor PDGFRα-Fc and its peptide derivatives have been shown to inhibit cell-free HCMV infection, it is unclear whether they can also impede the cellassociated growth of the virus. This is important because recent clinical isolates of HCMV spread strictly cell-associated in cell culture [23][24][25][26] and this mode of spreading is thought to be important for dissemination within a host once the infection is established [27][28][29]. Cell-associated spread is common in enveloped viruses [30], and is assumed to improve transmission efficiency by increasing the local concentration of the virus at sites of cell-cell contact.…”

Section: Introductionmentioning

confidence: 99%

Peptide Derivatives of Platelet-Derived Growth Factor Receptor Alpha Inhibit Cell-Associated Spread of Human Cytomegalovirus

Braun¹,

Fischer²,

Sampaio³

et al. 2021

Viruses

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Cell-free human cytomegalovirus (HCMV) can be inhibited by a soluble form of the cellular HCMV-receptor PDGFRα, resembling neutralization by antibodies. The cell-associated growth of recent HCMV isolates, however, is resistant against antibodies. We investigated whether PDGFRα-derivatives can inhibit this transmission mode. A protein containing the extracellular PDGFRα-domain and 40-mer peptides derived therefrom were tested regarding the inhibition of the cell-associated HCMV strain Merlin-pAL1502, hits were validated with recent isolates, and the most effective peptide was modified to increase its potency. The modified peptide was further analyzed regarding its mode of action on the virion level. While full-length PDGFRα failed to inhibit HCMV isolates, three peptides significantly reduced virus growth. A 30-mer version of the lead peptide (GD30) proved even more effective against the cell-free virus, and this effect was HCMV-specific and depended on the viral glycoprotein O. In cell-associated spread, GD30 reduced both the number of transferred particles and their penetration. This effect was reversible after peptide removal, which allowed the synchronized analysis of particle transfer, showing that two virions per hour were transferred to neighboring cells and one virion was sufficient for infection. In conclusion, PDGFRα-derived peptides are novel inhibitors of the cell-associated spread of HCMV and facilitate the investigation of this transmission mode.

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Pathogenesis of human cytomegalovirus in the immunocompromised host

Cited by 363 publications

References 155 publications

How Viruses Use the VCP/p97 ATPase Molecular Machine

How Viruses Use the VCP/p97 ATPase Molecular Machine

How Viruses Use the VCP/p97 ATPase Molecular Machine

Peptide Derivatives of Platelet-Derived Growth Factor Receptor Alpha Inhibit Cell-Associated Spread of Human Cytomegalovirus

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