Targeting Epigenetics to Cure HIV-1: Lessons From (and for) Cancer Treatment

Svensson, J. Peter

doi:10.3389/fcimb.2021.668637

Cited by 5 publications

(2 citation statements)

References 114 publications

(136 reference statements)

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“…On the other hand, the observed dysregulation of genes related to the nucleosome and histone modifications may impact cellular epigenetics, potentially affecting the binding of transcription factors or the cell transcriptome (23,24). The chromatin remodeling induced by HIV has been previously reported to have the potential to affect several cellular pathways and promote latency in viral reservoirs (25)(26)(27)(28). The dysregulation of this mechanism in the MesLN could be further studied to elucidate whether it could be one potential cause of the formation of a larger SIV reservoir.…”

Section: Discussionmentioning

confidence: 99%

Lymphoid tissues contribute to viral clonotypes present in plasma at early post-ATI in SIV-infected rhesus macaques

Solis-Leal,

Boby,

Mallick

et al. 2023

Preprint

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The rebound-competent viral reservoir (RCVR), comprised of virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after antiretroviral therapy interruption (ATI), remains the biggest obstacle to the eradication of HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop targeted therapeutic strategies for reducing the RCVR. In this study, barcoded SIVmac239M was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood, lymphoid tissues (LTs, spleen, mesenteric and inguinal lymph nodes), and non-lymphoid tissues (NLTs, colon, ileum, lung, liver, and brain) were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX/RNAscope/in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy although plasma viral RNA remained < 22 copies/mL. Among the tissues studied, mesenteric and inguinal lymph nodes, and spleen contained viral barcodes detected in plasma, and trended to have higher cell-associated viral loads, higher intact provirus levels, and greater diversity of viral barcodes. CD4+ T cells were the main cell type harboring viral RNA (vRNA) after ATI. Further, T cell zones in LTs showed higher vRNA levels than B cell zones for most animals. These findings are consistent with LTs contributing to virus present in plasma early after ATI.

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Section: Discussionmentioning

confidence: 99%

Lymphoid tissues contribute to viral clonotypes present in plasma at early post-ATI in SIV-infected rhesus macaques

Solis-Leal,

Boby,

Mallick

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…On the other hand, the observed dysregulation of genes related to the nucleosome and histone modifications may affect cellular epigenetics, potentially affecting the binding of transcription factors or the cell transcriptome (27). The chromatin remodeling induced by HIV has been previously reported to have the potential to affect several cellular pathways and promote latency in viral reservoirs (28)(29)(30). The dysregulation of this mechanism in the MesLNs could be further studied to elucidate whether it could be one potential cause of the formation of a larger SIV reservoir.…”

Section: Discussionmentioning

confidence: 99%

Lymphoid tissues contribute to plasma viral clonotypes early after antiretroviral therapy interruption in SIV-infected rhesus macaques

Solis-Leal,

Boby,

Mallick

et al. 2023

Sci. Transl. Med.

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The rebound-competent viral reservoir, composed of a virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after ART interruption (ATI), remains the biggest obstacle to treating HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop therapeutic strategies for reducing the rebound-competent viral reservoir. In this study, barcoded simian immunodeficiency virus (SIV), SIVmac239M, was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood and tissues from secondary lymphoid organs (spleen, mesenteric lymph nodes, and inguinal lymph nodes) and from the colon, ileum, lung, liver, and brain were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX and RNAscope in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy, although plasma viral RNA remained below 22 copies per milliliter. Among the tissues studied, mesenteric lymph nodes, inguinal lymph nodes, and spleen contained viral barcodes detected in plasma. CD4 + T cells were the main cell type harboring viral RNA after ATI. Furthermore, T cell zones in lymphoid tissues showed higher viral RNA abundance than B cell zones for most animals. These findings are consistent with lymphoid tissues contributing to the virus present in plasma early after ATI.

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Human microbiomes in cancer development and therapy

Xia

Liu

et al. 2023

MedComm

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Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy. We also insight into the molecular mechanisms of triggering, promoting, or inhibiting carcinogenesis and disease progress induced by microbiomes or/and their secretions of bioactive metabolites. And then, the strategies of application of microorganisms in cancer treatment were discussed in detail. However, the mechanisms by which human microbiomes function are still poorly understood. The bidirectional interactions between microbiotas and endocrine systems need to be clarified. Probiotics and prebiotics are believed to benefit human health via a variety of mechanisms, in particular, in tumor inhibition. It is largely unknown how microbial agents cause cancer or how cancer progresses. We expect this review may open new perspectives on possible therapeutic approaches of patients with cancer.

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Targeting Epigenetics to Cure HIV-1: Lessons From (and for) Cancer Treatment

Cited by 5 publications

References 114 publications

Lymphoid tissues contribute to viral clonotypes present in plasma at early post-ATI in SIV-infected rhesus macaques

Lymphoid tissues contribute to viral clonotypes present in plasma at early post-ATI in SIV-infected rhesus macaques

Lymphoid tissues contribute to plasma viral clonotypes early after antiretroviral therapy interruption in SIV-infected rhesus macaques

Human microbiomes in cancer development and therapy

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