The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication

Ziehr, Ben; Lenarcic, Erik M.; Cecil, Chad; Moorman, Nathaniel J.

doi:10.1016/j.virol.2015.12.009

Cited by 20 publications

(18 citation statements)

References 41 publications

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“…2k, human lung implant cells isolated from TB40/E-infected LoM were also Percolled. HCMV DNA levels in PB and tissue cells were measured by real-time PCR analysis as previously described 73 .…”

Section: Competing Interestsmentioning

confidence: 99%

Precision mouse models with expanded tropism for human pathogens

et al. 2019

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Section: Competing Interestsmentioning

confidence: 99%

Precision mouse models with expanded tropism for human pathogens

et al. 2019

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“…Total RNA was extracted using TRIzol according to the manufacturer's directions as described previously (47,48). Briefly, cell pellets were resuspended in TRIzol and extracted with chloroform, and RNA was precipitated with isopropanol.…”

Section: Cells and Virusesmentioning

confidence: 99%

“…Polysomes and polysome-associated RNAs were isolated as described previously (47,48). Briefly, at the time of harvest, cells were incubated in normal growth medium containing 0.1 mg/ml cycloheximide (CHX) for 10 min.…”

Section: Cells and Virusesmentioning

confidence: 99%

Multiple Transcripts Encode Full-Length Human Cytomegalovirus IE1 and IE2 Proteins during Lytic Infection

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Ziehr

Vincent

et al. 2016

J Virol

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Expression of the human cytomegalovirus (HCMV) IE1 and IE2 proteins is critical for the establishment of lytic infection and reactivation from viral latency. Defining the mechanisms controlling IE1 and IE2 expression is therefore important for understanding how HCMV regulates its replicative cycle. Here we identify several novel transcripts encoding full-length IE1 and IE2 proteins during HCMV lytic replication. Two of the alternative major immediate early (MIE) transcripts initiate in the first intron, intron A, of the previously defined MIE transcript, while others extend the 5= untranslated region. Each of the MIE transcripts associates with polyribosomes in infected cells and therefore contributes to IE1 and IE2 protein levels. Surprisingly, deletion of the core promoter region of the major immediate early promoter (MIEP) from a plasmid containing the MIE genomic locus did not completely abrogate IE1 and IE2 expression. Instead, deletion of the MIEP core promoter resulted in increased expression of alternative MIE transcripts, suggesting that the MIEP suppresses the activity of the alternative MIE promoters. While the canonical MIE mRNA was the most abundant transcript at immediate early times, the novel MIE transcripts accumulated to levels equivalent to that of the known MIE transcript later in infection. Using two HCMV recombinants, we found that sequences in intron A of the previously defined MIE transcript are required for efficient IE1 and IE2 expression and viral replication. Together, our results identify new regulatory sequences controlling IE1 and IE2 expression and suggest that multiple transcription units act in concert to regulate IE1 and IE2 expression during lytic infection. IMPORTANCEThe HCMV IE1 and IE2 proteins are critical regulators of HCMV replication, both during primary infection and reactivation from viral latency. This study expands our understanding of the sequences controlling IE1 and IE2 expression by defining novel transcriptional units controlling the expression of full-length IE1 and IE2 proteins. Our results suggest that alternative promoters may allow for IE1 and IE2 expression when MIEP activity is limiting, as occurs in latently infected cells. The human cytomegalovirus (HCMV) IE1 and IE2 proteins are critical regulators of the viral replicative cycle. Both proteins are immediately expressed upon infection and together stimulate the expression of host and viral genes necessary for virus replication (1). IE2 acts as a general transcription factor that broadly transactivates host genes and viral early and late genes to facilitate virus replication (2-12). IE1 promotes transcription from the HCMV genome by inhibiting histone deactylases (HDACs) (13-15), which otherwise limit virus transcription by forming inhibitory chromatin structures on the viral genome. Reexpression of IE1 and IE2 is also thought to be critical for the reactivation of quiescent HCMV genomes from latent infection. Thus, understanding the regulatory mechanisms controlling IE1 and IE2 expression is im...

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“…The results demonstrated that eIF4AIII was a common target of three of the lncRNAs. The RNA helicase eIF4AIII plays important roles in human cytomegalovirus replication . Our results showed the potential influence of eIF4AIII on another herpesvirus, EBV, implying that EBV could probably modulate its own replication by dysregulating a few host lncRNAs.…”

Section: Discussionmentioning

confidence: 70%

“…The RNA helicase eIF4AIII plays important roles in human cytomegalovirus replication. [48][49][50] Our results showed the potential influence of eIF4AIII on another herpesvirus, EBV, implying that EBV could probably modulate its own replication by dysregulating a few host lncRNAs. The identification and elucidation of the mechanism of this interaction is underway in our continuing work.…”

Section: Target Genes Of the Ebv-related Lncrnasmentioning

confidence: 66%

Differential expression profiling of lncRNAs related to Epstein‐Barr virus infection in the epithelial cells

Zhang

Zuo

et al. 2019

Journal of Medical Virology

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Epstein‐Barr virus (EBV) is a prevalent γ‐herpesvirus associated with a variety of cancers, including epithelial nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). Long noncoding RNAs (lncRNAs) are emerging as powerful regulators that have demonstrated to play crucial roles in cancer development. In this approach, based on genome‐wide RNA sequencing, we examined the lncRNA expression profiles in four EBV genome‐infected and EBV‐negative 293 cells. A series of lncRNAs were found to be dysregulated in a comparative analysis. Then, eight typical lncRNAs were selected for validation of expression levels by real‐time quantitative polymerase chain reaction and were detected in EBV‐positive or EBV‐negative GC and NPC cells. The differential expression patterns of the eight lncRNAs for validation were fundamentally identical to those revealed in RNA sequencing. Particularly, the differential expression of these lncRNAs in GC and NPC cells indicated their possible roles in EBV infection and tumorigenesis. In addition, a predicted lncRNA‐microRNA‐messenger RNA network suggested their potential interactions. This study reveals the first lncRNAome related to EBV infection in the epithelial cells and provides novel clues for the study of viral role in epithelial cancers through the interaction between EBV and host lncRNAs.

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The eIF4AIII RNA helicase is a critical determinant of human cytomegalovirus replication

Cited by 20 publications

References 41 publications

Precision mouse models with expanded tropism for human pathogens

Precision mouse models with expanded tropism for human pathogens

Multiple Transcripts Encode Full-Length Human Cytomegalovirus IE1 and IE2 Proteins during Lytic Infection

Differential expression profiling of lncRNAs related to Epstein‐Barr virus infection in the epithelial cells

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