MicroRNAs expressed by human cytomegalovirus

Zhang, Lichen; Yu, Jiaqi; Liu, Zhijun

doi:10.1186/s12985-020-1296-4

Cited by 34 publications

(30 citation statements)

References 82 publications

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“…UL138 has long and short isoforms, both of which suppress major IE gene transcription and promote latency (Lee et al, 2016). Hcmv-miR-UL36 down-regulates HCMV UL138, indicating that hcmv-miR-UL36 may be a new latent period-related determinant of viral miRNAs contributing to HCMV replication (Huang et al, 2013;Zhang et al, 2020). The protein isoforms encoded by UL136 regulates the latent and replication states of infection, whereas the complex interaction between UL136 subtypes balances the replication and latency period of HCMV (Caviness et al, 2016).…”

Section: Latencymentioning

confidence: 99%

Functional Profile of Human Cytomegalovirus Genes and Their Associated Diseases: A Review

Qian

et al. 2020

Front. Microbiol.

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The human cytomegalovirus (HCMV), whose genome is 235 ± 1.9 kbp long, is a common herpesvirus. However, the functions of many of its genes are still unknown. HCMV is closely associated with various human diseases and infects 60-90% of the global population. It can infect various human cells, including fibroblasts, epithelial cells, endothelial cells, smooth muscle cells, and monocytes. Although HCMV infection is generally asymptomatic and causes subtle clinical symptoms, it can generate a robust immune response and establish a latent infection in immunocompromised individuals, including those with AIDS, transplant recipients, and developing fetuses. Currently available antivirals approved for the treatment of HCMV-associated diseases are limited by dose-limiting toxicity and the emergence of resistance; however, vaccines and immunoglobulins are unavailable. In this review, we have summarized the recent literature on 43 newly identified HCMV genes. We have described their novel functions on the viral replication cycle, latency, and host immune evasion. Further, we have discussed HCMV-associated diseases and current therapeutic targets. Our review may provide a foundational basis for studies aiming to prevent and develop targeted therapies for HCMV-associated diseases.

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Section: Latencymentioning

confidence: 99%

Functional Profile of Human Cytomegalovirus Genes and Their Associated Diseases: A Review

Qian

et al. 2020

Front. Microbiol.

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“…Only few herpesvirus miRNA promoters are well characterized in literature [ 43 – 46 ]. MiRNAs encoded by human cytomegalovirus (HCMV) are found interspersed within the viral genome and hence their expression is regulated via promoters of adjacent viral genes [ 47 , 48 ]. Epstein Barr virus (EBV) encodes for 2 distinct groups/clusters of miRNAs (EBV BART and BHRF1 miRNAs) which are localized in the intronic regions of longer transcripts and therefore share a common promoter with BART and BHRF1 transcripts respectively [ 32 , 49 , 50 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although, KSHV miRNA cluster was earlier reported to be expressed via a distal promoter present upstream of LANA [ 51 ], Pearce et al (2005) indicates presence of a proximal promoter coinciding with v-Cyclin and v-FLIP transcription units [ 58 ]. HCMV miR-US33 is encoded in conjunction with US33 gene and hence, share a common promoter [ 47 , 59 ]. HCMV miR-US33 represses viral DNA replication in the host by binding to the 3′ UTR of host syntaxin mRNA [ 60 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of G-quadruplexes upstream of herpesvirus miRNAs: evidence of G-quadruplex mediated regulation of KSHV miR-K12–1-9,11 cluster and HCMV miR-US33

Kumar

Choudhary

Patra

et al. 2020

BMC Mol and Cell Biol

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Background G-quadruplexes regulate gene expression, recombination, packaging and latency in herpesviruses. Herpesvirus-encoded miRNAs have been linked to important biological functions. The presence and the biological role of G-quadruplexes have not been studied in the regulatory regions of virus miRNA. We hypothesized that herpesvirus-encoded miRNAs are regulated by G-quadruplexes in their promoters. Results We analyzed the 1 kb regulatory regions of all herpesvirus-encoded miRNAs for the presence of putative quadruplex-forming sequences (PQS). Over two-third (67%) of the regulatory regions of herpesvirus miRNAs had atleast 1 PQS. The 200 bp region of the promoter proximal to herpesvirus miRNA is particularly enriched for PQS. We chose to study the G-quadruplex motifs in the promoters of miR-K12 cluster in Kaposi's sarcoma-associated Herpesvirus (KSHV miR-K12–1-9,11) and the miR-US33 encoded by Human Cytomegalovirus (HCMV miR-US33). Biophysical characterization indicates that the G-quadruplex motifs in the promoters of the KSHV miR-K12 cluster and the HCMV miR-US33 form stable intramolecular G-quadruplexes in vitro. Mutations disrupting the G-quadruplex motif in the promoter of the KSHV miR-K12 cluster significantly inhibits promoter activity, while those disrupting the motif in the promoter of HCMV miR-US33 significantly enhance the promoter activity as compared to that of the respective wild-type promoter. Similarly, the addition of G-quadruplex binding ligands resulted in the modulation of promoter activity of the wild-type promoters (with intact G-quadruplex) but not the mutant promoters (containing quadruplex-disrupting mutations). Conclusion Our findings highlight previously unknown mechanisms of regulation of virus-encoded miRNA and also shed light on new roles for G-quadruplexes in herpesvirus biology.

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“…The role of HCMV miRNAs and their potential mechanism of infection have been recently reviewed by Zhang [17] and Piedade and Azevedo-Pereira [18]. Currently, seven HCMV-encoded miRNAs have been reported to target potential mediators of immune evasion to improve viral replication.…”

Section: Introductionmentioning

confidence: 99%

“…miR-UL148D is also able to target the activating receptor type-1B (ACVR1B) in monocytes, resulting in a reduced secretion of IL-6 [24]. miR-UL22A-5p and miR-UL22A-3p play a significant role in immune modulation [17]. miR-UL22A-5p has been predicted to target bone morphogenetic protein receptor type 2 (BMPR2), a receptor involved in alternative polarization in macrophages [25].…”

Section: Introductionmentioning

confidence: 99%

Impact of Natural Occurring ERAP1 Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection

D’Amico

Tempora

Lucarini

et al. 2020

IJMS

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Human cytomegalovirus (HCMV) is a β-herpesvirus that causes serious problems in people with a compromised immune system, whereas it coexists asymptomatically within the host with a healthy immune system. Like other viruses, HCMV has adopted multiples strategies to manipulate the host’s immune responses. Among them, expression of viral microRNAs (miRNAs) is one of the most intriguing. HCMV miR-UL112-5p and miR-US4-1 have been found to contribute to immune evasion by targeting the endoplasmic reticulum aminopeptidase 1 (ERAP1), a highly polymorphic key component of antigen processing. The current incomplete picture on the interplay between viral miRNAs and host immunity implies the need to better characterize the host genetic determinants. Naturally occurring single nucleotide polymorphisms (SNPs) within the miRNA binding sites of target genes may affect miRNA–target interactions. In this review, we focus on the relevance of 3′ untranslated region (3′UTR) ERAP1 SNPs within miRNA binding sites in modulating miRNA–mRNA interactions and the possible consequent individual susceptibility to HCMV infection. Moreover, we performed an in silico analysis using different bioinformatic algorithms to predict ERAP1 variants with a putative powerful biological function. This evidence provides a basis to deepen the knowledge on how 3′UTR ERAP1 variants may alter the mechanism of action of HCMV miRNAs, in order to develop targeted antiviral therapies.

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MicroRNAs expressed by human cytomegalovirus

Cited by 34 publications

References 82 publications

Functional Profile of Human Cytomegalovirus Genes and Their Associated Diseases: A Review

Functional Profile of Human Cytomegalovirus Genes and Their Associated Diseases: A Review

Analysis of G-quadruplexes upstream of herpesvirus miRNAs: evidence of G-quadruplex mediated regulation of KSHV miR-K12–1-9,11 cluster and HCMV miR-US33

Impact of Natural Occurring ERAP1 Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection

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