The microRNA Transcriptome of Human Cytomegalovirus (HCMV)

Meshesha, Mesfin; Veksler-Lublinsky, Isana; Isakov, Ofer; Reichenstein, Irit; Shomron, Noam; Kedem, Klara; Ziv-Ukelson, Michal; Bentwich, Zvi; Avni, Yonat Shemer

doi:10.2174/1874357901206010038

Cited by 38 publications

(52 citation statements)

References 35 publications

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“…In two of the miRNAs detected during latency, we observed an interesting shift in abundance equilibrium between the leading (miRNA) and the passenger (miRNA*) arms of the microRNA hairpins. Both arms of mir-US29, are expressed during lytic infection of HCMV in fibroblasts, but the 5p arm is the dominant one (Meshesha et al, 2012;Stark et al, 2012). However, in PBMC/ monocytes of latently infected people, we could not detect the 5p arm, while the 3p arm was readily detectable and was among the most highly expressed HCMV miRNAs during latency (Figs.…”

Section: In Vivo Expression Of Hcmv Micrornas During Latencymentioning

confidence: 85%

“…In contrast, five microRNAs, miR-UL112-3p, miR-UL36-5p, miR-UL22A-5p, miR-US29-3p and miR-US22-5p were expressed throughout these infection phases. miR-UL112-3p and miR-US29-3p were the most abundant microRNAs at all times of infection, unlike in HFF cells where relative abundance varies over the course infection (Meshesha et al, 2012). MiR-US22-5p was the second-most highly expressed microRNA during latency in THP-1 cells while during lytic infection in HFF cells, this microRNA was only moderately expressed compared to other miRNAs.…”

Section: Hcmv Mirrnas Associated With Transition To Latencymentioning

confidence: 89%

“…RT-PCR was run on Light Cycler 480 system (Roche Applied Science, Manheim, Germany). Detection of microRNAs by qPCR and forward primers used are described in (Meshesha et al, 2012).…”

Section: Genesmentioning

confidence: 99%

“…The first 11 microRNA precursors from HCMV were discovered using cloning techniques and computational approaches (Pfeffer et al, 2005;Dunn et al, 2005;Grey et al, 2005). Using deep sequencing of short RNAs from HCMV infected Human Foreskin Fibroblast (HFF) cells, we and others discovered ten additional microRNAs of which six were from four novel precursors and four were from already known precursors (Meshesha et al, 2012;Stark et al, 2012). To date, 26 mature microRNAs of HCMV have been deposited in the miRBase and are scattered along both strands of its genome.…”

Section: Introductionmentioning

confidence: 99%

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In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency

Meshesha

Bentwich

Solomon

et al. 2016

Gene

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Section: In Vivo Expression Of Hcmv Micrornas During Latencymentioning

confidence: 85%

Section: Hcmv Mirrnas Associated With Transition To Latencymentioning

confidence: 89%

“…RT-PCR was run on Light Cycler 480 system (Roche Applied Science, Manheim, Germany). Detection of microRNAs by qPCR and forward primers used are described in (Meshesha et al, 2012).…”

Section: Genesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency

Meshesha

Bentwich

Solomon

et al. 2016

Gene

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“…Most of these differences were located in the nonessential or noncoding regions of the genome, which are known to accumulate mutations during passaging (30). These changes did not overlap the known microRNA and noncoding RNAs that are present in the HCMV genome (31)(32)(33). When the UL96P10 and Towne-BAC viruses were compared, most noticeable were two point mutations in the UL96 region of the genome at positions 171699 and 171819 (Table 1).…”

Section: Figmentioning

confidence: 99%

Highly Acidic C-Terminal Region of Cytomegalovirus pUL96 Determines Its Functions during Virus Maturation Independently of a Direct pp150 Interaction

Brechtel¹,

Mocarski²,

Tandon³

2014

J Virol

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Tegument proteins pp150 and pUL96 function at a late step in cytomegalovirus (CMV) maturation. Here, we show that pp150 interacts directly with pUL96; however, the N-terminal region of pp150 and the C-terminal region of pUL96, which are critical for these proteins to function, are not required for this interaction. Moreover, the largely dispensable C-terminal region of pp150 is critical for pp150-pUL96 interaction. To further study the role of pUL96, several point and clustered mutations were engineered into the CMV Towne bacterial artificial chromosome (Towne-BAC) genome, replacing the conserved negatively charged C-terminal residues of pUL96. Although individual point mutations (E 122 A, D 124 A, and D 125 A) reduced virus growth slightly, the clustered mutations of 122 EVDDAV 127 significantly reduced virus growth, produced small syncytial plaque phenotypes, and impacted a late stage of virus maturation. When the UL96 C-terminal alanine conversion mutant (B6-BAC) virus was serially passaged in cell culture, it gained a plaque size comparable to that of Towne-BAC, displayed an altered restriction fragment length pattern, and replicated with increased growth kinetics. Whole-genome sequencing of this passaged virus (UL96P10) and the similarly passaged Towne-BAC virus revealed major differences only in the RNA4.9 and UL96 regions. When one of the mutations in the UL96 coding region was engineered into the B6-BAC virus, it significantly increased the plaque size and rescued the virus growth rate. Thus, accumulation of compensatory mutations only in UL96 in this revertant and the specific involvement of functionally dispensable regions of pp150 in the pUL96-pp150 interaction point toward a role for pUL96 in virus maturation that does not depend upon pp150. IMPORTANCEHuman cytomegalovirus causes significant medical problems in newborns, as well as in people with low immunity. In this study, we investigated the functions of two essential virus proteins, pp150 and pUL96, and determined the impact of their mutual interaction on virus replication. These studies provide valuable information that is critical for the development of targeted antiviral therapies. The proteinaceous layer between the capsid and the envelope in a herpesvirus virion, known as the tegument, is analogous to the matrix layer found in some RNA viruses. Tegument proteins function in at least four different ways; they (i) are delivered into host cells upon virus entry as prepackaged transactivation factors that can promote infection, e.g., cytomegalovirus (CMV) pp71 (1, 2); (ii) are critical for the acquisition of the virus envelope and act as a bridge between the nucleocapsids and the envelope layer (3, 4); (iii) provide capsid stability during virus maturation and trafficking, e.g., CMV pp150 and pUL96 (5, 6); and (iv) help in the trafficking of virus in the cell by engaging the host cytoskeleton, e.g., herpes simplex virus (HSV) UL36 (7-9). Herpesvirus tegument has been thought to be amorphous in nature (3, 4, 10), although a more ordered s...

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The panorama of miRNA-mediated mechanisms in mammalian cells

Stroynowska-Czerwinska

Fiszer

Krzyżosiak

2014

Cell. Mol. Life Sci.

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MicroRNAs comprise a large family of short, non-coding RNAs that are present in most eukaryotic organisms and are typically involved in downregulating the expression of protein-coding genes. The detailed mechanisms of miRNA functioning in animals and plants have been under investigation for more than decade. In mammalian cells, miRNA guides the effector complex miRISC to bind with partially complementary sequences, usually within the 3′UTR of mRNAs, and inhibit protein synthesis with or without transcript degradation. In addition to these main mechanisms, several other modes of miRNA-mediated gene expression regulation have been described, but their scale and importance remain a matter of debate. In this review, we briefly summarize the pathway of miRNA precursor processing during miRNA biogenesis and continue with the description of the miRISC assembly process. Then, we present the miRNA-mediated mechanisms of gene expression regulation in detail, and we gather information concerning the proteins involved in these processes. In addition, we briefly refer to the current applications of miRNA mechanisms in therapeutic strategies. Finally, we highlight some of the remaining controversies surrounding the regulation of mammalian gene expression by miRNAs.

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The microRNA Transcriptome of Human Cytomegalovirus (HCMV)

Cited by 38 publications

References 35 publications

In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency

In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency

Highly Acidic C-Terminal Region of Cytomegalovirus pUL96 Determines Its Functions during Virus Maturation Independently of a Direct pp150 Interaction

The panorama of miRNA-mediated mechanisms in mammalian cells

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