Mechanism and factors that control HIV-1 transcription and latency activation

Liu, Rongdiao; Wu, Jun; Shao, Rui; Xue, Yuhua

doi:10.1631/jzus.b1400059

Cited by 21 publications

(11 citation statements)

References 87 publications

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“…The RNA polymerase III transcription initiation pathway is represented by the GTF3C genes cluster (Figure 2). Upon integration into the human genome, HIV-1 RNA transcription is mediated by RNA polymerase II (41). Though the product of the GTF3C3 gene has been linked to upregulation of HIV-1 RNA (40), in addition to mRNA synthesis, HIV-1 specific small nuclear RNAs can also be produced from RNA polymerase III promoters (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Whole Genome Rare-Variant Association Study of HIV-1 Progression in a Southern African Population

Thami

Choga

Mulisa

et al. 2020

Preprint

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Despite the high burden of HIV-1 in Botswana, the population of Botswana is significantly underrepresentation in host genetics studies of HIV-1. Furthermore, the bulk of previous genomics studies evaluated common human genetic variations, however, there is increasing evidence of the influence of rare variants in the outcome of diseases which may be uncovered by comprehensive complete and deep genome sequencing. This research aimed to evaluate the role of rare-variants in susceptibility to HIV-1 and progression through whole genome sequencing. Whole genome sequences (WGS) of 265 HIV-1 positive and 125 were HIV-1 negative unrelated individuals from Botswana were mapped to the human reference genome GRCh38. Population joint variant calling was performed using Genome Analysis Tool Kit (GATK) and BCFTools. Cumulative effects of rare variant sets on susceptibility to HIV-1 and progression (CD4+ T-cell decline) were determined with optimized Sequence Kernel Association Test (SKAT-O). In silico functional analysis of the prioritized variants was performed through gene-set enrichment using databases in GeneMANIA and Enrichr. Novel rare-variants within the ANKRD39 (8.48 × 10−8), LOC105378523 (7.45 × 10−7) and GTF3C3 (1.36 × 10−6) genes were significantly associated with HIV-1 progression. Functional analysis revealed that these genes are involved in viral translation and transcription. These findings highlight the significance of whole genome sequencing in pinpointing rare-variants of clinical relevance. The research contributes towards a deeper understanding of the host genetics HIV-1 and offers promise of population specific interventions against HIV-1.

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Section: Discussionmentioning

confidence: 99%

Whole Genome Rare-Variant Association Study of HIV-1 Progression in a Southern African Population

Thami

Choga

Mulisa

et al. 2020

Preprint

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“…Similarly in an earlier study, we found that NFAT4 inhibition decreases NF-κB-stimulated early transcription and also JCV replication (Wollebo et al 2012). For other viruses, Wang et al (2013) reported that Brd4 was required for human papillomavirus type 16 DNA replication and Brd4 is also involved in the replication of HIV-1 (Liu et al 2014; Mbonye and Karn 2014) and Merkel cell polyomavirus (Wang et al 2012) as described below.…”

Section: Discussionmentioning

confidence: 99%

“…Brd4 has also been implicated in the reactivation of latent HIV-1 (Liu et al 2014; Mbonye and Karn 2014). P-TEFb was first identified as a specific host cofactor required for HIV-1 transcription (Marshall and Price 1995).…”

Section: Discussionmentioning

confidence: 99%

The Brd4 acetyllysine-binding protein is involved in activation of polyomavirus JC

et al. 2016

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Brd4 is an epigenetic reader protein and a member of the BET (bromodomain and extra terminal domain) family of proteins with two bromodomains that recognize acetylated lysine residues. Brd4 specifically binds to acetylated transcription factor NF-κB p65 and coactivates transcription. Polyomavirus JC (JCV) is regulated by a noncoding control region (NCCR) containing promoter/enhancer elements for viral gene expression including a binding site for NF-κB, which responds to proinflammatory cytokines such as TNF-α, the DNA damage response, calcium signaling and acetylation of the NF-κB p65 subunit on lysine residues K218 and K221. Earlier studies indicated that NF-κB is involved in the reactivation of persistent/latent JCV in glial cells to cause progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the brain caused by replication of JCV in glial cells. To investigate the mechanism of action of NF-κB acetylation on JCV transcription, we examined Brd4 and found that JCV early transcription was stimulated by Brd4 via the JCV NF-κB site and that p65 K218 and K221 were involved. Treatment with the Brd4 inhibitor JQ1(+) or mutation of either K218 or K221 to glutamine (K218R or K221) inhibited this stimulation and decreased the proportion of p65 in the nucleus. We conclude that Brd4 is involved in the regulation of the activation status of JCV in glial cells.

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“…Besides, the kinase-inactivated complex also contains Lupus antigen (La)-related protein 7 (LARP7), a methyl phosphate capping enzyme called MePCE, AF9, AFF1, AFF4, ENL, ELL1, and ELL2. Together, this entire complex is known as super elongation complex (SEC) (Nguyen et al, 2001;Yik et al, 2004;He et al, 2010;Liu et al, 2014). In an infected cell, the P-TEFb dissociates from the SEC and forms an association with the bromodomain-containing protein 4 (Brd4).…”

Section: Transcription and Latencymentioning

confidence: 99%

From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1

et al. 2020

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HIV-1 employs a rich arsenal of viral factors throughout its life cycle and co-opts intracellular trafficking pathways. This exquisitely coordinated process requires precise manipulation of the host microenvironment, most often within defined subcellular compartments. The virus capitalizes on the host by modulating cell-surface proteins and cleverly exploiting nuclear import pathways for post entry events, among other key processes. Successful virus–cell interactions are indeed crucial in determining the extent of infection. By evolving defenses against host restriction factors, while simultaneously exploiting host dependency factors, the life cycle of HIV-1 presents a fascinating montage of an ongoing host–virus arms race. Herein, we provide an overview of how HIV-1 exploits native functions of the host cell and discuss recent findings that fundamentally change our understanding of the post-entry replication events.

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Mechanism and factors that control HIV-1 transcription and latency activation

Cited by 21 publications

References 87 publications

Whole Genome Rare-Variant Association Study of HIV-1 Progression in a Southern African Population

Whole Genome Rare-Variant Association Study of HIV-1 Progression in a Southern African Population

The Brd4 acetyllysine-binding protein is involved in activation of polyomavirus JC

From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1

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