RUNX1-mediated alphaherpesvirus-host trans-species chromatin interaction promotes viral transcription

Xiao, Ke; Xiong, Dan; Chen, Gong; Yu, Jinsong; Li, Yue; Chen, Kening; Zhang, Lu; Xu, Yangyang; Xu, Qian; Huang, Xi; Gao, Anran; Cao, Kai; Yan, Keji; Dai, Jinxia; Hu, Xueying; Ruan, Yijun; Fu, Zhenfang; Li, Guoliang; Cao, Gang

doi:10.1126/sciadv.abf8962

Cited by 13 publications

(8 citation statements)

References 50 publications

(53 reference statements)

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“…Various types of viruses, including HBV (8)(9)(10)(11), Epstein-Barr virus (EBV) (12), human papillomavirus (HPV) (13), human herpesviruses (HHV) (14), influenza A virus (IAV) (15), human leukemia virus (HTLV-1) (16), and parvoviruses (17), have been reported to have interactions with the genome 3D organization [as reviewed in (18)]. The genome 3D organization coordinately regulated multiple genes expression by 3D chromatin structures, topologically associating domains (TADs, Mbp-scale genomic regions) and A/B compartments (composed of groups of TADs) (19,20).…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional and single-cell sequencing of liver cancer reveals comprehensive host-virus interactions in HBV infection

et al. 2023

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BackgroundsHepatitis B virus (HBV) infection is a major risk factor for chronic liver diseases and liver cancer (mainly hepatocellular carcinoma, HCC), while the underlying mechanisms and host-virus interactions are still largely elusive.MethodsWe applied HiC sequencing to HepG2 (HBV-) and HepG2-2.2.15 (HBV+) cell lines and combined them with public HCC single-cell RNA-seq data, HCC bulk RNA-seq data, and both genomic and epigenomic ChIP-seq data to reveal potential disease mechanisms of HBV infection and host-virus interactions reflected by 3D genome organization.ResultsWe found that HBV enhanced overall proximal chromatin interactions (CIs) of liver cells and primarily affected regional CIs on chromosomes 13, 14, 17, and 22. Interestingly, HBV altered the boundaries of many topologically associating domains (TADs), and genes nearby these boundaries showed functional enrichment in cell adhesion which may promote cancer metastasis. Moreover, A/B compartment analysis revealed dramatic changes on chromosomes 9, 13 and 21, with more B compartments (inactive or closed) shifting to A compartments (active or open). The A-to-B regions (closing) harbored enhancers enriched in the regulation of inflammatory responses, whereas B-to-A regions (opening) were enriched for transposable elements (TE). Furthermore, we identified large HBV-induced structural variations (SVs) that disrupted tumor suppressors, NLGN4Y and PROS1. Finally, we examined differentially expressed genes and TEs in single hepatocytes with or without HBV infection, by using single-cell RNA-seq data. Consistent with our HiC sequencing findings, two upregulated genes that promote HBV replication, HNF4A and NR5A2, were located in regions with HBV-enhanced CIs, and five TEs were located in HBV-activated regions. Therefore, HBV may promote liver diseases by affecting the human 3D genome structure.ConclusionOur work promotes mechanistic understanding of HBV infection and host-virus interactions related to liver diseases that affect billions of people worldwide. Our findings may also have implications for novel immunotherapeutic strategies targeting HBV infection.

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Section: Introductionmentioning

confidence: 99%

Three-dimensional and single-cell sequencing of liver cancer reveals comprehensive host-virus interactions in HBV infection

et al. 2023

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“…Alphaherpesviruses, the most common viruses in the world, can establish a lytic or latent infection in the peripheral nervous system of the host [ 22 ]. During the establishment of a latent infection, herpesviruses are maintained as epistomes in the nucleus of the host cell [ 23 ]. To elucidate the mechanisms of the latent infection and reactivation of alphaherpesviruses, several in vivo and in vitro models have been developed.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an In Vitro Model of Pseudorabies Virus Latency and Reactivation and Identification of Key Viral Latency-Associated Genes

Pan

Zhang

et al. 2023

Viruses

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Alphaherpesviruses infect humans and most animals. They can cause severe morbidity and mortality. The pseudorabies virus (PRV) is a neurotropic alphaherpesvirus that can infect most mammals. The PRV persists in the host by establishing a latent infection, and stressful stimuli can induce the latent viruses to reactivate and cause recurrent diseases. The current strategies of antiviral drug therapy and vaccine immunization are ineffective in eliminating these viruses from the infected host. Moreover, overspecialized and complex models are also a major obstacle to the elucidation of the mechanisms involved in the latency and reactivation of the PRV. Here, we present a streamlined model of the latent infection and reactivation of the PRV. A latent infection established in N2a cells infected with the PRV at a low multiplicity of infection (MOI) and maintained at 42 °C. The latent PRV was reactivated when the infected cells were transferred to 37 °C for 12 to 72 h. When the above process was repeated with a UL54-deleted PRV mutant, it was observed that the UL54 deletion did not affect viral latency. However, viral reactivation was limited and delayed. This study establishes a powerful and streamlined model to simulate PRV latency and reveals the potential role of temperature in PRV reactivation and disease. Meanwhile, the key role of the early gene UL54 in the latency and reactivation of PRV was initially elucidated.

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“…After DNase treatment, reverse transcription was performed using the ReverTra Ace qPCR RT Master Mix kit (TOYOBO, Shanghai, China). The qPCR primer sequences were designed according to Genebank [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

The Activity of Plant-Derived Ren’s Oligopeptides-1 against the Pseudorabies Virus

Xiao

Cai

et al. 2022

Animals

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Newly synthesized Ren’s oligopeptides-1 was found to have an antiviral effect in clinical trials, and the purpose of this study was to further demonstrate the antiviral activity of Ren’s oligopeptides-1 against the PRV 152-GFP strain. We used the real-time cell analysis system (RTCA) to detect the cytotoxicity of different concentrations of Ren’s oligopeptides-1. We then applied high content screening (HCS) to detect the antiviral activity of Ren’s oligopeptides-1 against PRV. Meanwhile, the fluorescence signal of the virus was collected in real time and the expression levels of the related genes in the PK15 cells infected with PRV were detected using real-time PCR. At the mRNA level, we discovered that, at a concentration of 6 mg/mL, Ren’s oligopeptides-1 reduced the expression of pseudorabies virus (PRV) genes such as IE180, UL18, UL54, and UL21 at a concentration of 6 mg/mL. We then determined that Ren’s oligopeptides-1 has an EC50 value of 6 mg/mL, and at this level, no cytotoxicity was observed.

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RUNX1-mediated alphaherpesvirus-host trans-species chromatin interaction promotes viral transcription

Cited by 13 publications

References 50 publications

Three-dimensional and single-cell sequencing of liver cancer reveals comprehensive host-virus interactions in HBV infection

Three-dimensional and single-cell sequencing of liver cancer reveals comprehensive host-virus interactions in HBV infection

Establishment of an In Vitro Model of Pseudorabies Virus Latency and Reactivation and Identification of Key Viral Latency-Associated Genes

The Activity of Plant-Derived Ren’s Oligopeptides-1 against the Pseudorabies Virus

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