Human cytomegalovirus latency-associated protein LUNA is expressed during HCMV infections in vivo

Bego, Mariana G.; Keyes, Lisa R.; Maciejewski, Jaroslaw P.; Jeor, Stephen C. St.

doi:10.1007/s00705-011-1027-7

Cited by 19 publications

(23 citation statements)

References 22 publications

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“…Indeed, it has been presumed that viral gene expression during latency is restricted to a subset of RNAs or proteins that promote the latent infection or restrict replication. Examples of these in HSV-1 and HCMV latency include the latency-associated transcripts (LATs) that have long been thought of as the molecular hallmark of HSV latency [20, 21], viral gene products encoded in the ULb’ region of the HCMV genome (e.g., the UL133–UL138 locus) [22–24], and HCMV LUNA (Latency Unique Natural Antigen) [25, 26]. The specific role(s) of these genes in the establishment of longer term maintenance of latency is not yet fully understood.…”

Section: A Classical View Of Herpesvirus Latencymentioning

confidence: 99%

The Loss of Binary: Pushing the Herpesvirus Latency Paradigm

Collins-McMillen

Goodrum

2017

Curr Clin Micro Rpt

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Purpose of Review Herpesvirus latency has been viewed as a binary state where replication is either on or off. During latency, gene expression is thought to be restricted to non-coding RNAs or very few proteins so that the virus avoids detection by the immune system. However, a number of recent studies across herpesvirus families call into question the existence of a binary switch for latency, and suggest that latency is far more dynamic than originally presumed. These studies are the focus of this review. Recent Findings Highly sensitive and global approaches to investigate viral gene expression in the context of latency have revealed low level viral transcripts, and in some cases protein, from each of the three kinetic gene classes during the latent alpha and beta herpesvirus infection either in vitro or in vivo. Further, low level, asymptomatic virus shedding persists following acute infection. Together, these findings have raised questions about how silent the latent infection truly is. Summary Emerging evidence suggests that viral gene expression associated with latent states may be broader and more dynamic than originally presumed during herpesvirus latency. This is an important possibility to consider in understanding the molecular programs associated with the establishment, maintenance and reactivation of herpesvirus latency. Here, we review these findings and detail how they contribute to the emergence of a biphasic model of reactivation.

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Section: A Classical View Of Herpesvirus Latencymentioning

confidence: 99%

The Loss of Binary: Pushing the Herpesvirus Latency Paradigm

Collins-McMillen

Goodrum

2017

Curr Clin Micro Rpt

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“…Upon differentiation stimuli, latent virus can reactivate and re-enter the lytic life cycle resulting in the production of infectious virions (Soderberg-Naucler et al, 1997; Zhuravskaya et al, 1997; Hahn et al, 1998; Soderberg-Naucler et al, 2001; Goodrum et al, 2002; Reeves et al, 2005; Huang et al, 2012). During latency, HCMV remains present as an episome and produces a limited set of transcripts (Bolovan-Fritts et al, 1999; Goodrum et al, 2002; Bego et al, 2005; Cheung et al, 2006; Goodrum et al, 2007; Petrucelli et al, 2009; Avdic et al, 2011; Bego et al, 2011; Keyes et al, 2012; Poole et al, 2013; Rossetto et al, 2013). …”

Section: Novel Functional Annotations Of Hcmv Genes Expressed During mentioning

confidence: 99%

“…A number of transcripts were found in more than one study, i.e., RL7, UL3, UL67, UL68, UL84, UL87, UL108, UL110, UL133, UL135, US28 (Beisser et al, 2002; Goodrum et al, 2002; Cheung et al, 2006; Keyes et al, 2012; Rossetto et al, 2013) but thus far only UL81ast/LUNA (Goodrum et al, 2002; Bego et al, 2005, 2011; Keyes et al, 2012; Rossetto et al, 2013), UL111A (Cheung et al, 2006; Avdic et al, 2011; Rossetto et al, 2013), UL138 (Goodrum et al, 2002, 2007; Petrucelli et al, 2009; Rossetto et al, 2013) and, depending on the virus used and the presence of GATA transcription binding sites, UL144 (Poole et al, 2013) were extensively characterized as LATs. Further research will show the validity of other potential LATs and dive deeper into the actual function of these transcripts and possibly their gene products during HCMV latency.…”

Section: Novel Functional Annotations Of Hcmv Genes Expressed During mentioning

confidence: 99%

Functional annotation of human cytomegalovirus gene products: an update

Damme

Loock

2014

Front. Microbiol.

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Human cytomegalovirus is an opportunistic double-stranded DNA virus with one of the largest viral genomes known. The 235 kB genome is divided in a unique long (UL) and a unique short (US) region which are flanked by terminal and internal repeats. The expression of HCMV genes is highly complex and involves the production of protein coding transcripts, polyadenylated long non-coding RNAs, polyadenylated anti-sense transcripts and a variety of non-polyadenylated RNAs such as microRNAs. Although the function of many of these transcripts is unknown, they are suggested to play a direct or regulatory role in the delicately orchestrated processes that ensure HCMV replication and life-long persistence. This review focuses on annotating the complete viral genome based on three sources of information. First, previous reviews were used as a template for the functional keywords to ensure continuity; second, the Uniprot database was used to further enrich the functional database; and finally, the literature was manually curated for novel functions of HCMV gene products. Novel discoveries were discussed in light of the viral life cycle. This functional annotation highlights still poorly understood regions of the genome but more importantly it can give insight in functional clusters and/or may be helpful in the analysis of future transcriptomics and proteomics studies.

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“…Of the more than 200 genes encoded by the HCMV genome, for example, only 5 are expressed during latent infection (3)(4)(5)(6)(7). Transcriptional silencing of the HCMV major immediate early promoter (MIEP) is a key step in establishing HCMV latency (8)(9)(10)(11)(12)(13)(14).…”

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confidence: 99%

Host MicroRNA Regulation of Human Cytomegalovirus Immediate Early Protein Translation Promotes Viral Latency

O’Connor

Vaníček

Murphy

2014

J Virol

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Reactivation of human cytomegalovirus (HCMV) is a significant cause of disease and death in immunocompromised patients, underscoring the need to understand how latency is controlled. Here we demonstrate that HCMV has evolved to utilize cellular microRNAs (miRNAs) in cells that promote latency to regulate expression of a viral protein critical for viral reactivation. Our data reveal that hsa-miR-200 miRNA family members target the UL122 (immediate early protein 2) 3= untranslated region, resulting in repression of this viral protein. Utilizing recombinant viruses that mutate the miRNA-binding site compared to the sequence of the wild-type virus results in lytic rather than latent infections in ex vivo infections of primary CD34 ؉ cells. Cells permissive for lytic replication demonstrate low levels of these miRNAs. We propose that cellular miRNA regulation of HCMV is critical for maintenance of viral latency. IMPORTANCEHuman cytomegalovirus (HCMV) is a herpesvirus that infects a majority of the population. Once acquired, individuals harbor the virus for life, where the virus remains, for the most part, in a quiet or latent state. Under weakened immune conditions, the virus can reactivate, which can cause severe disease and often death. We have found that members of a family of small RNAs, termed microRNAs, encoded by human myeloid progenitor cells are capable of repressing a key viral protein, thus enabling the virus to ensure a quiet/latent state. As these progenitor cells mature further down the myeloid lineage toward cells that support active viral replication, the levels of these microRNAs decrease. Together, our data suggest that host cell microRNA regulation of HCMV is important for the quiet/latent state of this pathogen.

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Human cytomegalovirus latency-associated protein LUNA is expressed during HCMV infections in vivo

Cited by 19 publications

References 22 publications

The Loss of Binary: Pushing the Herpesvirus Latency Paradigm

The Loss of Binary: Pushing the Herpesvirus Latency Paradigm

Functional annotation of human cytomegalovirus gene products: an update

Host MicroRNA Regulation of Human Cytomegalovirus Immediate Early Protein Translation Promotes Viral Latency

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