Phosphorylation-tuned condensation links HCMV tegument assembly to membrane recruitment

Jensen, Y.; Cortez Rayas, L.; Bogdanow, B.; Gruska, I. B.; Vetter, B.; Caragliano, E.; Muehlberg, L.; von Einem, J.; Wiebusch, L.; Bosse, J. B.

doi:10.64898/2026.08.05.743017

bioRxiv · 10.64898/2026.08.05.743017

Phosphorylation-tuned condensation links HCMV tegument assembly to membrane recruitment

Jensen, Y.·Cortez Rayas, L.·Bogdanow, B.·Gruska, I. B.·Vetter, B.·Caragliano, E.·Muehlberg, L.·von Einem, J.·Wiebusch, L.·Bosse, J. B.

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Abstract

Herpesviruses build complex infectious particles around a protein layer, the tegument, that lacks an ordered architecture. How this apparently amorphous material selectively assembles on the capsid and engages enveloping membranes remains unclear. Here we show that the capsid-anchored human cytomegalovirus protein pp150 forms liquid-like condensates when locally concentrated. Its disordered region recruits soluble tegument proteins and membrane-associated partners, providing a mechanism to couple assembly of the tegument layer to recruitment of the enclosing membrane. Phosphorylation tunes this condensation: phosphomimetic mutations prevent recovery of infectious virus, whereas loss of phosphorylation sites causes aberrant capsid-tegument assemblies and impairs viral replication. Together, these findings identify regulated condensation as a mechanism that couples tegument assembly to membrane recruitment and supports the production of infectious particles, highlighting condensate regulation as a potentially novel point of antiviral intervention.

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Jensen, Y., Cortez Rayas, L., Bogdanow, B., Gruska, I. B., Vetter, B., Caragliano, E., Muehlberg, L., von Einem, J., Wiebusch, L., Bosse, J. B.. 2026-08-05. Phosphorylation-tuned condensation links HCMV tegument assembly to membrane recruitment. https://doi.org/10.64898/2026.08.05.743017

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