HCMV Assembly Is Totally Tubular

Lyon, Shelby M.; Kalejta, Robert F.

doi:10.1016/j.devcel.2018.03.014

Cited by 3 publications

(1 citation statement)

References 9 publications

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“…From the perspective of scRNA-seq analysis of cell complexity in the mammalian kidney, prior studies have largely focused on the developing mouse 8,17 and human kidney 6,18 , or a specific lineage within the adult mouse kidney 11 . However, a recent large scale scRNA-seq analysis of adult organs in the mouse, included 6665 single cells from the kidney 19 .…”

Section: How Does This Study Compare With Prior Studies?mentioning

confidence: 99%

Single-Cell RNA Sequencing of the Adult Mouse Kidney: From Molecular Cataloging of Cell Types to Disease-Associated Predictions

Lindström

Brandine

Ransick

et al. 2019

American Journal of Kidney Diseases

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Section: How Does This Study Compare With Prior Studies?mentioning

confidence: 99%

Single-Cell RNA Sequencing of the Adult Mouse Kidney: From Molecular Cataloging of Cell Types to Disease-Associated Predictions

Lindström

Brandine

Ransick

et al. 2019

American Journal of Kidney Diseases

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Viral determinants influencing intra- and intercellular communication in cytomegalovirus infection

Wijs

Deželjin

Bogdanow

et al. 2023

Current Opinion in Virology

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Stabilizing microtubules aids neurite structure and disrupts syncytia formation in human cytomegalovirus-infected human forebrain neurons

Adelman,

Sukowaty,

Partridge

et al. 2024

Preprint

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Human cytomegalovirus (HCMV) is a prolific human herpesvirus that infects most individuals by adulthood. While typically asymptomatic in adults, congenital infection can induce serious neurological symptoms including hearing loss, visual deficits, cognitive impairment, and microcephaly in 10-15% of cases. HCMV has been shown to infect most neural cells with our group recently demonstrating this capacity in stem cell-derived forebrain neurons. Infection of neurons induces deleterious effects on calcium dynamics and electrophysiological function paired with gross restructuring of neuronal morphology. Here, we utilize an iPSC-derived model of the human forebrain to demonstrate how HCMV infection induces syncytia, drives neurite retraction, and remodels microtubule networks to promote viral production and release. We establish that HCMV downregulates microtubule associated proteins at 14 days postinfection while simultaneously sparing other cytoskeletal elements, and this includes HCMV-driven alterations to microtubule stability. Further, we pharmacologically modulate microtubule dynamics using paclitaxel (stabilize) and colchicine (destabilize) to examine the effects on neurite structure, syncytial morphology, assembly compartment formation, and viral release. With paclitaxel, we found improvement of neurite outgrowth with a corresponding disruption to HCMV-induced syncytia formation and Golgi network disruptions but with limited impact on viral titers. Together, these data suggest that HCMV infection-induced disruption of microtubules in human cortical neurons can be partially mitigated with microtubule stabilization, suggesting a potential avenue for future neuroprotective therapeutic exploration.

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HCMV Assembly Is Totally Tubular

Cited by 3 publications

References 9 publications

Single-Cell RNA Sequencing of the Adult Mouse Kidney: From Molecular Cataloging of Cell Types to Disease-Associated Predictions

Single-Cell RNA Sequencing of the Adult Mouse Kidney: From Molecular Cataloging of Cell Types to Disease-Associated Predictions

Viral determinants influencing intra- and intercellular communication in cytomegalovirus infection

Stabilizing microtubules aids neurite structure and disrupts syncytia formation in human cytomegalovirus-infected human forebrain neurons

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