biostudies-literatureBatra RNHGRI NIH HHSNCI NIH HHSNINDS NIH HHSNIGMS NIH HHS1101-1110https://www.ebi.ac.uk/biostudies/studies/S-EPMC5140759biostudies-literatureUnknown23(12)Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions (3' UTRs) and lengthening of poly(A)-tails in host gene transcripts. We found that the host RNA-binding protein CPEB1 was highly induced after infection, and ectopic expression of CPEB1 in noninfected cells recapitulated infection-related post-transcriptional changes. CPEB1 was also required for poly(A)-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reversed infection-related cytopathology and post-transcriptional changes, and decreased productive HCMV titers. Host RNA processing was also altered in herpes simplex virus-2 (HSV-2)-infected cells, thereby indicating that this phenomenon might be a common occurrence during herpesvirus infections. We anticipate that our work may serve as a starting point for therapeutic targeting of host RNA-binding proteins in herpesvirus infections.Nature structural & molecular biologyRNA-binding protein CPEB1 remodels host and viral RNA landscapes.PMC5140759R01 NS075449U54 HG007005P30 CA023100R01 HG004659T32 GM008666Bos TJDonohue JPRigo FHuelga SCBelzile JPHuang HSathe SSpector DHWheeler ECYeo GWAres MBatra RStark TJAigner SGelboin-Burkhart CYee BARoberts BTClark AEfalseRNA-binding protein CPEB1 remodels host and viral RNA landscapes.Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions (3' UTRs) and lengthening of poly(A)-tails in host gene transcripts. We found that the host RNA-binding protein CPEB1 was highly induced after infection, and ectopic expression of CPEB1 in noninfected cells recapitulated infection-related post-transcriptional changes. CPEB1 was also required for poly(A)-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reversed infection-related cytopathology and post-transcriptional changes, and decreased productive HCMV titers. Host RNA processing was also altered in herpes simplex virus-2 (HSV-2)-infected cells, thereby indicating that this phenomenon might be a common occurrence during herpesvirus infections. We anticipate that our work may serve as a starting point for therapeutic targeting of host RNA-binding proteins in herpesvirus infections.2016-01-01T00:00:00Z2016 Dec2024-10-18T13:55:59.131Z2019-03-27T02:30:53ZS-EPMC51407592777570910.1038/nsmb.3310