Activation of HIV-1 proviruses increases downstream chromatin accessibility

Shah, Raven; Gallardo, Christian M.; Jung, Yoonhee; Clock, Ben; Dixon, Jesse R.; McFadden, William M.; Majumder, Kinjal; Pintel, David J.; Corcés, Victor G.; Torbett, Bruce E.; Tedbury, Philip R.; Sarafianos, Stefan G.

doi:10.1016/j.isci.2022.105490

Cited by 8 publications

(4 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our hypothesis is further supported when considering that the integration site of HIV-1 is not random, but occurs with higher frequency in active gene regions near the nuclear periphery 1,3 . A previous report demonstrates that proviral activation of HIV-1 alters chromatin accessibility of neighboring genes 80 . Further experiments, such as ChIP-Seq or ATAC-Seq, would be helpful to pinpoint the specific motifs or DNA elements that play a role in directing Gag trafficking within the nucleus and whether Gag itself alters nearby chromatin structure.…”

Section: Discussionmentioning

confidence: 98%

HIV-1 Gag colocalizes with euchromatin histone marks at the nuclear periphery

Chang

Parent

2023

Preprint

View full text Add to dashboard Cite

The retroviral Gag protein of human immunodeficiency virus type 1 (HIV-1) plays a central role in the selection of unspliced viral genomic RNA for packaging into new virions. Previously, we demonstrated that full-length HIV-1 Gag undergoes nuclear trafficking where it associates with unspliced viral RNA (vRNA) at transcription sites. To further explore the kinetics of HIV-1 Gag nuclear localization, we used biochemical and imaging techniques to examine the timing of HIV-1 entry into the nucleus. We also aimed to determine more precisely Gag's subnuclear distribution to test the hypothesis that Gag would be associated with euchromatin, the transcriptionally active region of the nucleus. We observed that HIV-1 Gag localized to the nucleus shortly after its synthesis in the cytoplasm, suggesting that nuclear trafficking was not strictly concentration-dependent. Furthermore, we found that HIV-1 Gag preferentially localized to the transcriptionally active euchromatin fraction compared to the heterochromatin-rich region in a latently-infected CD4+ T cell line (J-Lat 10.6) treated with latency-reversal agents. Interestingly, HIV-1 Gag was more closely associated with transcriptionally-active histone markers near the nuclear periphery, where the HIV-1 provirus was previously shown to integrate. Although the precise function of Gag's association with histones in transcriptionally-active chromatin remains uncertain, together with previous reports, this finding is consistent with a potential role for euchromatin-associated Gag molecules to select newly transcribed unspliced vRNA during the initial stage of virion assembly.

show abstract

Section: Discussionmentioning

confidence: 98%

HIV-1 Gag colocalizes with euchromatin histone marks at the nuclear periphery

Chang

Parent

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…An increasing number of studies have found that viral infection affects the chromatin accessibility of animal hosts (Cao et al, 2022;Kong et al, 2020;Xu et al, 2020). HIV-1 alters the local cellular chromatin structure and the expression of neighbouring host genes (Shah et al, 2022;Wong et al, 2023). Many (8791) chromatin regions were found to be uniquely open in calves challenged with bovine respiratory syncytial virus (Johnston et al, 2021) to infection, such as autophagy, which is reported to be involved in RSV infection (Fu et al, 2018;Jiang et al, 2021;Li et al, 2021;Yu et al, 2021;Zhang, Wan, et al, 2023;Zhao et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Integrated ATAC‐seq and RNA‐seq data analysis identifies transcription factors related to rice stripe virus infection in Oryza sativa

Li,

Zhang

et al. 2024

Molecular Plant Pathology

View full text Add to dashboard Cite

Animal studies have shown that virus infection causes changes in host chromatin accessibility, but little is known about changes in chromatin accessibility of plants infected by viruses and its potential impact. Here, rice infected by rice stripe virus (RSV) was used to investigate virus‐induced changes in chromatin accessibility. Our analysis identified a total of 6462 open‐ and 3587 closed‐differentially accessible chromatin regions (DACRs) in rice under RSV infection by ATAC‐seq. Additionally, by integrating ATAC‐seq and RNA‐seq, 349 up‐regulated genes in open‐DACRs and 126 down‐regulated genes in closed‐DACRs were identified, of which 34 transcription factors (TFs) were further identified by search of upstream motifs. Transcription levels of eight of these TFs were validated by reverse transcription‐PCR. Importantly, four of these TFs (OsWRKY77, OsWRKY28, OsZFP12 and OsERF91) interacted with RSV proteins and are therefore predicted to play important roles in RSV infection. This is the first application of ATAC‐seq and RNA‐seq techniques to analyse changes in rice chromatin accessibility caused by RSV infection. Integrating ATAC‐seq and RNA‐seq provides a new approach to select candidate TFs in response to virus infection.

show abstract

“…Host 3D genome structures have also been characterized at the tethering sites of several episomal tumor viruses, including EBV, KSHV, and HBV, revealing cell type- and virus-specific variations 20 , 25 , 30 , 31 . In the context of integrating viruses such as human T-lymphotropic virus type 1 (HTLV), human immunodeficiency virus (HIV), and HPV, insertion of ectopic viral DNA into host chromosomes has been shown to alter cellular genomic loops and TAD structures 32 – 38 . Host 3D genome changes have also been observed for several viruses that do not interact with their host nuclear genome, such as SARS-CoV-2 and influenza A viruses, but modulate 3D genome changes through the action of viral proteins and other unidentified factors that are yet to be fully understood 39 – 41 (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, HIV does not contain a CTCF binding site; integration occurs more frequently at CTCF-enriched TADS, and depletion of CTCF reduces integration efficiency 101 , 102 . The state of the host chromatin and location of integration are crucial factors influencing HIV-1 gene regulation 37 , 38 . Analysis of Hi–C data obtained from tissue samples of individuals with HIV encephalitis (HIVE) revealed a notable association between transcriptional derepression of interferon signaling and cell migratory pathways, as did a shift in A/B compartment structures from B to A 37 .…”

Section: Introductionmentioning

confidence: 99%

Viral remodeling of the 4D nucleome

Kim,

Lieberman

2024

Exp Mol Med

View full text Add to dashboard Cite

The dynamic spatial organization of genomes across time, referred to as the four-dimensional nucleome (4DN), is a key component of gene regulation and biological fate. Viral infections can lead to a reconfiguration of viral and host genomes, impacting gene expression, replication, latency, and oncogenic transformation. This review provides a summary of recent research employing three-dimensional genomic methods such as Hi–C, 4C, ChIA-PET, and HiChIP in virology. We review how viruses induce changes in gene loop formation between regulatory elements, modify chromatin accessibility, and trigger shifts between A and B compartments in the host genome. We highlight the central role of cellular chromatin organizing factors, such as CTCF and cohesin, that reshape the 3D structure of both viral and cellular genomes. We consider how viral episomes, viral proteins, and viral integration sites can alter the host epigenome and how host cell type and conditions determine viral epigenomes. This review consolidates current knowledge of the diverse host-viral interactions that impact the 4DN.

show abstract

Activation of HIV-1 proviruses increases downstream chromatin accessibility

Cited by 8 publications

References 127 publications

HIV-1 Gag colocalizes with euchromatin histone marks at the nuclear periphery

HIV-1 Gag colocalizes with euchromatin histone marks at the nuclear periphery

Integrated ATAC‐seq and RNA‐seq data analysis identifies transcription factors related to rice stripe virus infection in Oryza sativa

Viral remodeling of the 4D nucleome

Contact Info

Product

Resources

About