Understanding the regulation of APOBEC3 expression: Current evidence and much to learn

Covino, Daniela Angela; Gauzzi, Maria Cristina; Fantuzzi, Laura

doi:10.1002/jlb.2mr0717-310r

Cited by 28 publications

(21 citation statements)

References 81 publications

(250 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IFNs are main inducers of APOBEC3 expression (55). Our previous work suggested that CCL2 neutralization-mediated increase of APOBEC3A expression in MDMs was type I IFN independent (20,56).…”

Section: Discussionmentioning

confidence: 95%

Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression

et al. 2020

Self Cite

View full text Add to dashboard Cite

Macrophages are key targets of human immunodeficiency virus type 1 (HIV-1) infection and main producers of the proinflammatory chemokine CC chemokine ligand 2 (CCL2), whose expression is induced by HIV-1 both in vitro and in vivo. We previously found that CCL2 neutralization in monocyte-derived macrophages (MDMs) strongly inhibited HIV-1 replication affecting post-entry steps of the viral life cycle. Here, we used RNAsequencing to deeply characterize the cellular factors and pathways modulated by CCL2 blocking in MDMs and involved in HIV-1 replication restriction. We report that exposure to CCL2 neutralizing antibody profoundly affected the MDM transcriptome. Functional annotation clustering of up-regulated genes identified two clusters enriched for antiviral defense and immune response pathways, comprising several interferonstimulated, and restriction factor coding genes. Transcripts in the clusters were enriched for RELA and NFKB1 targets, suggesting the activation of the canonical nuclear factor κB pathway as part of a regulatory network involving miR-155 up-regulation. Furthermore, while HIV-1 infection caused small changes to the MDM transcriptome, with no evidence of host defense gene expression and type I interferon signature, CCL2 blocking enabled the activation of a strong host innate response in infected macrophage cultures, and potently inhibited viral genes expression. Notably, an inverse correlation was found between levels of viral transcripts and of the restriction factors APOBEC3A (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 A),

show abstract

Section: Discussionmentioning

confidence: 95%

Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…[33][34][35][36] Distinct pathways of transcriptional regulation have been characterized to date for A3A, A3B, and A3G. 37 Virus-cell interactions are characterized for the cancer-associated human papillomavirus (HPV) and polyomavirus that can inactivate specific components of the E2F transcription factor network to de-repress A3B transcription. 38,39 HPV-16 E6 protein also upregulates A3B transcription.…”

Section: Introductionmentioning

confidence: 99%

The von Hippel–Lindau Cullin-RING E3 ubiquitin ligase regulates APOBEC3 cytidine deaminases

Scholtés

Sawyer

Vaca

et al. 2021

Translational Research

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

“…The strongest inducers of APOBEC3 expression are interferons (IFN) (Covino et al, 2018). In the current study, the levels of IFNα and IFNγ in cell supernatant may have been insufficient to induce APOBEC3 expression.…”

Section: Discussionmentioning

confidence: 99%

Differences in HBV Replication, APOBEC3 Family Expression, and Inflammatory Cytokine Levels Between Wild-Type HBV and Pre-core (G1896A) or Basal Core Promoter (A1762T/G1764A) Mutants

et al. 2020

View full text Add to dashboard Cite

Background: Chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) worldwide. HBV variants, particularly the G1896A precore (PC) and A1762T/G1764A basal core promoter (BCP) mutations, are established risk factors for cirrhosis and HCC, but the molecular biological basis is unclear. We hypothesized that these variants result in differential HBV replication, APOBEC3 family expression, and cytokine/chemokine expression. Methods: HepG2 cells were transfected with monomeric full-length containing wildtype, PC, or BCP HBV. Cells and supernatant were collected to analyze viral infection markers (i.e., HBsAg, HBeAg, HBV DNA, and RNA). Cellular APOBEC3 expression and activity was assessed by quantitative real-time (qRT)-PCR, immunoblot, differential DNA denaturation PCR, and sequencing. Cytokine/chemokines in the supernatant and in serum from 11 CHB carriers (4 non-cirrhotic; 7 cirrhotic and/or HCC) with predominantly wild-type, PC, or BCP variants were evaluated by Luminex. Results: HBeAg expression was reduced in PC and BCP variants, and higher supernatant HBV DNA and HBV RNA levels were found with A1762T/G1764A vs. G1896A mutant (p < 0.05). Increased APOBEC3G protein levels in wild-type vs. mutant were not associated with HBV covalently closed circular DNA G-to-A hypermutations. Differences in cytokine/chemokine expression in culture supernatants, especially IL-13 were observed amongst the variants analyzed. Noticeable increases of numerous

show abstract

Understanding the regulation of APOBEC3 expression: Current evidence and much to learn

Cited by 28 publications

References 81 publications

Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression

Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression

The von Hippel–Lindau Cullin-RING E3 ubiquitin ligase regulates APOBEC3 cytidine deaminases

Differences in HBV Replication, APOBEC3 Family Expression, and Inflammatory Cytokine Levels Between Wild-Type HBV and Pre-core (G1896A) or Basal Core Promoter (A1762T/G1764A) Mutants

Contact Info

Product

Resources

About