HIV–1 infection reduces NAD capping of host cell snRNA and snoRNA

Benoni, Barbora; Benoni, Roberto; Trylčová, Jana; Grab, Katarzyna; Pačes, Jan; Weber, Jan; Staněk, David; Kowalska, Joanna; Bednářová, Lucie; Keckesova, Zuzana; Gahurová, Lenka; Cahová, Hana

doi:10.1101/2022.11.10.515957

Cited by 4 publications

(5 citation statements)

References 66 publications

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“…Furthermore, our analysis is focusing mostly in CGs, leaving open the possibility that methylation of the other patterns (CHG or CHH) occurs, even though the analysis of the few targets presented in this study doesn't support this. Nevertheless, we cannot exclude that even small CG methylation differences are capable of affecting phenotype and viroid infectious cycle, as has been demonstrated in cases like epitranscriptomics (Benoni et al, 2022). Finally, we need to point out that under these experimental conditions we cannot tell if the resulting effect is beneficial for the viroid's biological cycle or if it is just the outcome of the stress caused by infection.…”

Section: Discussionmentioning

confidence: 94%

PSTVd infection in Nicotiana benthamiana plants has a minor yet detectable effect on CG methylation

Tselika,

Belmezos,

Kallemi

et al. 2023

Front. Plant Sci.

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Viroids are small circular RNAs infecting a wide range of plants. They do not code for any protein or peptide and therefore rely on their structure for their biological cycle. Observed phenotypes of viroid infected plants are thought to occur through changes at the transcriptional/translational level of the host. A mechanism involved in such changes is RNA-directed DNA methylation (RdDM). Till today, there are contradictory works about viroids interference of RdDM. In this study, we investigated the epigenetic effect of viroid infection in Nicotiana benthamiana plants. Using potato spindle tuber viroid (PSTVd) as the triggering pathogen and via bioinformatic analyses, we identified endogenous gene promoters and transposable elements targeted by 24 nt host siRNAs that differentially accumulated in PSTVd-infected and healthy plants. The methylation status of these targets was evaluated following digestion with methylation-sensitive restriction enzymes coupled with PCR amplification, and bisulfite sequencing. In addition, we used Methylation Sensitive Amplification Polymorphism (MSAP) followed by sequencing (MSAP-seq) to study genomic DNA methylation of 5-methylcytosine (5mC) in CG sites upon viroid infection. In this study we identified a limited number of target loci differentially methylated upon PSTVd infection. These results enhance our understanding of the epigenetic host changes as a result of pospiviroid infection.

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Section: Discussionmentioning

confidence: 94%

PSTVd infection in Nicotiana benthamiana plants has a minor yet detectable effect on CG methylation

Tselika,

Belmezos,

Kallemi

et al. 2023

Front. Plant Sci.

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“…NOTCH4 is a transmembrane receptor of 2003 amino-acids, expressed ubiquitously, which has been associated with increased apoptosis in breast cancer ( 16 ) and increased inflammation in HIV-1 associated nephropathy ( 17 ). DXO is a decapping exoribonuclease, of size 396 AA, which leads to an increase of HIV-1 infectivity ( 18 ), its inactivation may thus favor protection against HIV-1 replication.…”

Section: Resultsmentioning

confidence: 99%

The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control

Rahmouni,

De Marco,

Spadoni

et al. 2023

Front. Immunol.

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IntroductionWe have reanalyzed the genomic data of the International Collaboration for the Genomics of HIV (ICGH), centering on HIV-1 Elite Controllers.MethodsWe performed a genome-wide Association Study comparing 543 HIV Elite Controllers with 3,272 uninfected controls of European descent. Using the latest database for imputation, we analyzed 35,552 Single Nucleotide Polymorphisms (SNPs) within the Major Histocompatibility Complex (MHC) region.ResultsOur analysis identified 2,626 SNPs significantly associated (p<5. 10-8) with elite control of HIV-1 infection, including well-established MHC signals such as the rs2395029-G allele which tags HLA-B*57:01. A thorough investigation of SNPs in linkage disequilibrium with rs2395029 revealed an extensive haploblock spanning 1.9 megabases in the MHC region tagging HLA-B*57:01, comprising 379 SNP alleles impacting 72 genes. This haploblock contains damaging variations in proteins like NOTCH4 and DXO and is also associated with a strong differential pattern of expression of multiple MHC genes such as HLA-B, MICB, and ZBTB12. The study was expanded to include two cohorts of seropositive African-American individuals, where a haploblock tagging the HLA-B*57:03 allele was similarly associated with control of viral load. The mRNA expression profile of this haploblock in African Americans closely mirrored that in the European cohort.DiscussionThese findings suggest that additional molecular mechanisms beyond the conventional antigen-presenting role of class I HLA molecules may contribute to the observed influence of HLA-B*57:01/B*57:03 alleles on HIV-1 elite control. Overall, this study has uncovered a large haploblock associated with HLA-B*57 alleles, providing novel insights into their massive effect on HIV-1 elite control.

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“…Dual-seq can reveal the intricate interplay of host and pathogen, but has not yet been applied to study these interactions on the level of the epitranscriptome. NAD-RNAs have only been indicated to exist during infection by the eukaryotic Dengue virus using LC-MS (7) and HIV-1 infection of human cells (26). Surprisingly, NAD is a key regulatory molecule in the interactions between phages and their bacterial hosts.…”

Section: Introductionmentioning

confidence: 99%

T4 phage RNA is NAD-capped and alters the NAD-cap epitranscriptome ofEscherichia coliduring infection through a phage-encoded decapping enzyme

Wolfram-Schauerte,

Moskalchuk,

Pozhydaieva

et al. 2024

Preprint

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Nicotinamide adenine dinucleotide (NAD) serves as a cap-like structure on cellular RNAs (NAD-RNAs) in all domains of life including the bacterium Escherichia coli. NAD also acts as a key molecule in phage-host interactions, where bacterial immune systems deplete NAD to abort phage infection. Nevertheless, NAD-RNAs have not yet been identified during phage infections of bacteria and the mechanisms of their synthesis and degradation are unknown in this context. The T4 phage that specifically infects E. coli presents an important model to study phage infections, but a systematic analysis of the presence and dynamics of NAD-RNAs during T4 phage infection is lacking. Here, we investigate the presence of NAD-RNAs during T4 phage infection in a dual manner. By applying time resolved NAD captureSeq, we identify NAD-capped host and phage transcripts and their dynamic regulation during phage infection. We provide evidence that NAD-RNAs are - as reported earlier - generated by the host RNA polymerase by initiating transcription with NAD at canonical transcription start sites. In addition, we characterize NudE.1 - a T4 phage-encoded Nudix hydrolase - as the first phage-encoded NAD-RNA decapping enzyme. T4 phages carrying inactive NudE.1 display a delayed lysis phenotype. This study investigates for the first time the dual epitranscriptome of a phage and its host, thereby introducing epitranscriptomics as an important field of phage research.

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HIV–1 infection reduces NAD capping of host cell snRNA and snoRNA

Cited by 4 publications

References 66 publications

PSTVd infection in Nicotiana benthamiana plants has a minor yet detectable effect on CG methylation

PSTVd infection in Nicotiana benthamiana plants has a minor yet detectable effect on CG methylation

The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control

T4 phage RNA is NAD-capped and alters the NAD-cap epitranscriptome ofEscherichia coliduring infection through a phage-encoded decapping enzyme

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