Correction for Avey et al., “Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36”

Avey, Denis; Tepper, Sarah; Pifer, Benjamin; Bahga, Amritpal; Williams, Hunter; Gillen, Joseph; Li, Wenwei; Ogden, Sarah; Zhu, Fanxiu

doi:10.1128/jvi.01484-17

Cited by 2 publications

(2 citation statements)

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“…Protein kinases are known to regulate myriad host and viral processes. Like other viruses, KSHV relies on virus-encoded [44] and host-encoded kinases for optimal lytic replication [19,21,22,45]. Some kinases regulate reactivation by altering LANA latent protein functions, lytic gene transcription and translation, and cell survival and proliferation [18-20, 23, 46-49].…”

Section: Discussionmentioning

confidence: 99%

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Olson

Kang

Ladha

et al. 2023

Preprint

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Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human diseases including Kaposi’s sarcoma (KS), a leading cause of cancer in Africa and in patients with AIDS. KS tumor cells harbor KSHV predominantly in a latent form, while typically <5% contain lytic replicating virus. Because both latent and lytic stages likely contribute to cancer initiation and progression, continued dissection of host regulators of this biological switch will provide insights into fundamental pathways controlling the KSHV life cycle and related disease pathogenesis. Several cellular protein kinases have been reported to promote or restrict KSHV reactivation, but our knowledge of these signaling mediators and pathways is incomplete. We employed a polypharmacology-based kinome screen to identifiy specific kinases that regulate KSHV reactivation. Those identified by the screen and validated by knockdown experiments included several kinases that enhance lytic reactivation: ERBB2 (HER2 or neu), ERBB3 (HER3), ERBB4 (HER4), MKNK2 (MNK2), ITK, TEC, and DSTYK (RIPK5). Conversely, ERBB1 (EGFR1 or HER1), MKNK1 (MNK1) and FRK (PTK5) were found to promote the maintenance of latency. Mechanistic characterization of ERBB2 pro-lytic functions revealed a signaling connection between ERBB2 and the activation of CREB1, a transcription factor that drives KSHV lytic gene expression. These studies provided a proof-of-principle application of a polypharmacology-based kinome screen for the study of KSHV reactivation and enabled the discovery of both kinase inhibitors and specific kinases that regulate the KSHV latent-to-lytic replication switch.

show abstract

Section: Discussionmentioning

confidence: 99%

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Olson

Kang

Ladha

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Protein kinases are known to regulate numerous host and viral processes. Like other viruses, KSHV relies on virus-encoded [75] and host-encoded kinases for optimal lytic replication [19,21,22,76]. Some kinases regulate reactivation by altering LANA latent protein functions, lytic gene transcription and translation, and cell survival and proliferation [18][19][20]23,[77][78][79][80].…”

Section: Discussionmentioning

confidence: 99%

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Olson,

Kang,

Ladha

et al. 2023

PLoS Pathog

View full text Add to dashboard Cite

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes several human diseases including Kaposi’s sarcoma (KS), a leading cause of cancer in Africa and in patients with AIDS. KS tumor cells harbor KSHV predominantly in a latent form, while typically <5% contain lytic replicating virus. Because both latent and lytic stages likely contribute to cancer initiation and progression, continued dissection of host regulators of this biological switch will provide insights into fundamental pathways controlling the KSHV life cycle and related disease pathogenesis. Several cellular protein kinases have been reported to promote or restrict KSHV reactivation, but our knowledge of these signaling mediators and pathways is incomplete. We employed a polypharmacology-based kinome screen to identify specific kinases that regulate KSHV reactivation. Those identified by the screen and validated by knockdown experiments included several kinases that enhance lytic reactivation: ERBB2 (HER2 or neu), ERBB3 (HER3), ERBB4 (HER4), MKNK2 (MNK2), ITK, TEC, and DSTYK (RIPK5). Conversely, ERBB1 (EGFR1 or HER1), MKNK1 (MNK1) and FRK (PTK5) were found to promote the maintenance of latency. Mechanistic characterization of ERBB2 pro-lytic functions revealed a signaling connection between ERBB2 and the activation of CREB1, a transcription factor that drives KSHV lytic gene expression. These studies provided a proof-of-principle application of a polypharmacology-based kinome screen for the study of KSHV reactivation and enabled the discovery of both kinase inhibitors and specific kinases that regulate the KSHV latent-to-lytic replication switch.

show abstract

Correction for Avey et al., “Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36”

Cited by 2 publications

References 0 publications

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

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