Human Cytomegalovirus Forms Phase-Separated Compartments at Viral Genomes to Facilitate Viral Replication

Caragliano, Enrico; Bonazza, Stefano; Frascaroli, Giada; Tang, Junhua; Soh, Timothy K.; Grünewald, Kay; Bosse, Jens B.; Brune, Wolfram

doi:10.2139/ssrn.3871395

Cited by 1 publication

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“…A recent functional genomics screen revealed perturbation of only two viral genes, namely UL69 and UL112, to create distinct, abortive trajectories 44 . UL112 has recently been shown to undergo liquid-liquid phase separation to form viral replication compartments in the nucleus 45 . It may thus not only be essential for viral genome replication but also facilitate recruitment of the transcriptional machinery to the replicating viral genomes.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics reveals principles of gene regulation and pervasive non-productive transcription in the human cytomegalovirus genome

Jürges¹,

Lodha²,

Le‐Trilling

et al. 2022

Preprint

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For decades, human cytomegalovirus (HCMV) was thought to express ≈200 viral proteins during lytic infection. In recent years, systems biology approaches uncovered hundreds of additional viral gene products and suggested thousands of viral sites of transcription initiation. Despite all available data, the molecular mechanisms of HCMV gene regulation remain poorly understood. Here, we provide a unifying model of productive HCMV gene expression employing transcription start site profiling combined with metabolic RNA labeling as well as integrative computational analysis of previously published big data. This approach defined the expression of >2,600 high confidence viral transcripts and explained the complex kinetics of viral protein expression by cumulative effects of translation of incoming virion-associated RNA, multiple transcription start sites with distinct kinetics per viral open reading frame, and differences in viral protein stability. Most importantly, we identify pervasive transcription of transient RNAs as a common feature of this large DNA virus with its human host.

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Section: Discussionmentioning

confidence: 99%