Biology subjects

Delerce, J.

Publications and source records attributed to Delerce, J..

5 recordsLinked to original sources

bioRxiv2023

Role of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic

RNA viruses, including SARS-CoV-2, evolve by mutation acquisition, or by hybridization between viral genomes. The SARS-CoV-2 pandemic provided an exceptional opportunity to analyze the mutations that appeared over a three-year period. In this study, we analysed the type of mutations and their epidemic consequences on the thousands of genomes produced in our laboratory. These were obtained by next-generation sequencing from respiratory samples performed for genomic surveillance. The frequencies of mutations were calculated using Nextclade, Microsoft Excel, and an in-house Python script. In total, 61,397 genomes matching 483 Pangolin lineages were analyzed; 22,225 nucleotide mutations were identified, and of them 220 (1.0%) were each at the root of at least 836 genomes, a frequency threshold classifying mutations as "hyperfertile". Two of these seeded the pandemic in Europe, namely a mutation in the RNA-dependent RNA polymerase associated with an increased mutation rate (P323L) and one in the spike protein (D614G), which plays a particular role in virus fitness. Most of these 220 "hyperfertile" mutations occurred in areas not predicted to be associated with increased virulence. Their number was 8{+/-}6 (0-22) per 1,000 nucleotides on average per gene. They were 3.7 times more frequent in accessory than informational genes (14 versus 4; p= 0.0037). Particularly, they were 4.1 times more frequent in ORF8 than in the gene encoding RNA polymerase. Interestingly, stop codons were present in 97 positions, almost only in six accessory genes including ORF7a (25 per 100 codons) and ORF8 (21). Furthermore, 1,661 mutations (16.3%) were associated with a lower number of "offspring" (50-835) and classified as "fertile". In conclusion, except for two initial mutations that could predict a change in the dynamics of the epidemic (mutation rate and change in the virus attachment site), most of the "hyperfertile" mutations did not predict the emergence of a new epidemic form. Significantly, some mutations were in non-coding areas and some consisted of stop codons, indicating that some genes (particularly ORF7a and ORF8) were rather "non-virulence genes" at a given stage of the epidemic, which is an unusual concept for viruses.

microbiology↗

bioRxiv2022

Sequencing of Monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection

An epidemic of Monkeypox virus (MPX virus) infections has arisen in May 2022 in non-endemic countries particularly in Europe among men having sex with men, whose extent is unprecedented. Since May 2022 we implemented MPX virus diagnosis by real-time PCR at university hospitals of Marseille, southern France. Here, we performed DNA metagenomic analyses of clinical samples from MPX virus-infected patients between June and July 2022, using next-generation sequencing with Illumina or Nanopore technologies. Twenty-five samples from 25 patients were studied. This allowed obtaining a MPX virus genome for 18 patients, essentially from genital skin lesions and rectal swabbing. All 18 genomes were classified in the MPX virus B.1 lineage, and we delineated five sublineages (A-E). We detected a high number of mutations (66-73) scattered along the MPX virus genomes relatively to the genome obtained from a human in Nigeria in 2018. Some non-synonymous mutations occurred in genes encoding central proteins, among which transcription factors and core and envelope proteins. They included two mutations that truncate RNA polymerase subunit RPO132 and a phospholipase D-like protein, which suggests gene inactivation. In addition, we identified that a large majority of nucleotide substitutions (94%) in the 18 MPX virus genomes were G>A or C>T, suggesting the action of human APOBEC3 enzymes. Finally, while we did not detect reads matching with main bacterial agents of sexually transmitted infections, >1,000 reads identified Staphylococcus aureus and Streptococcus pyogenes for 7 and 17 samples, respectively. These findings warrant a close genomic monitoring of MPX virus to get a better picture of this virus genetic evolution and mutational patterns, and they point out the common presence in monkeypox lesions of bacterial agents of skin superinfection, which warrants a close clinical monitoring in monkeypox patients.

microbiology↗

bioRxiv2020

Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients

The novel coronavirus (SARS-CoV-2) causes pandemic of viral pneumonia. The evolution and mutational events of the SARS-CoV-2 genomes are critical for controlling virulence, transmissibility, infectivity, severity of symptoms and mortality associated to this infectious disease. We collected and investigated 309 SARS-CoV-2 genomes from patients infected in France. Detailed genome cartography of all mutational events (SNPs, indels) was reported and correlated to clinical features of patients. A comparative analysis between our 309 SARS-CoV-2 genomes from French patients and the reference Wuhan coronavirus genome revealed 315 substitution mutations and six deletion events: ten were in 5/3 UTR, 178 were nonsynonymous, 126 were synonymous and one generated a stop codon. Six different deleted areas were also identified in nine viral variants. In particular, 30 substitution mutations (18 nonsynonymous) and one deletion ({Delta}21765-21770) concerned the spike S glycoprotein. An average of 7.8 mutational events (+/- 1.7 SD) and a median of 8 (range, 7-9) were reported per viral isolate. Comparative analyses and clustering of specific mutational signatures in 309 genomes disclose several divisions in groups and subgroups combining their geographical and phylogenetic origin. Clinical outcomes of the 309 COVID-19-infected patients were investigated according to the mutational signatures of viral variants. These findings highlight the genome dynamics of the coronavirus 2019-20 and shed light on the mutational landscape and evolution of this virus. Inclusion of the French cohort enabled us to identify 161 novel mutations never reported in SARS-CoV-2 genomes collected worldwide. These results support a global and continuing surveillance of the emerging variants of the coronavirus SARS-CoV-2.

genomics↗

bioRxiv2019

Lactobacillus reuteri: direct passage from ingested yogurts to urine microbiota

BackgroundSerendipitously, it was observed that fecal transplantation made for Clostridium difficile may cure chronic urinary tract infections. This led us to evaluate the passage in the urine of probiotics contained in yoghurt, which have been claimed to prevent urinary infections. ResultsA commercial yogurt that contained 3 probiotics (Bifidobacterium animalis, Lactobacillus delbrueckiii and Lactobacillus reuteri) was consumed by 28 healthy subjects. We performed by culturomics, urine analysis before and after feeding these yogurts. Genome sequencing of the bacterial strains absent before yogurt consumption and present after consumption was performed. Testing more than 40,000 colonies by MALDI-TOF, we observed in two men and one woman (11% of subjects included), the urine colonization of the same Lactobacillus reuteri present in yogurts, with the same genome with 50 genes never identified in other lactobacilli. ConclusionThis confirms that, as ingested, Lactobacillus salivarius passes into the milk of lactating women, some bacteria, particularly Lactobacillus can colonize body fluids previously considered sterile after ingestion via the digestive route. Although the consequences of this passage remain unknown, we prove for the first time that there is a digestive passage in the urine after consumption of probiotics, including fermented products sold commercially.

microbiology↗

bioRxiv2019

Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

Strategies to cure HIV-infected patients by virus-targeting drugs have failed to date. We identified a HIV-1-seropositive woman who spontaneously suppressed HIV replication and had normal CD4-cell counts, no HIV disease, no replication-competent virus and no cell HIV DNA detected with a routine assay. We suspected that dramatic HIV DNA degradation occurred postinfection. We performed multiple nested-PCRs followed by Sanger sequencing and applied a multiplex-PCR approach. Furthermore, we implemented a new technique based on two hybridization steps on beads prior to next-generation sequencing that removed human DNA then retrieved integrated HIV sequences with HIV-specific probes. We assembled {approx}45% of the HIV genome and further analyzed the G-to-A mutations putatively generated by cellular APOBEC3 enzymes that can change tryptophan codons into stop codons. We found more G-to-A mutations in the HIV DNA from the woman than in that of her contaminator. Moreover, 74% of the tryptophan codons were changed to stop codons (25%) or were deleted as a possible consequence of gene inactivation. Finally, we found that this womans cells remained HIV-susceptible in vitro. Our findings show that she does not exhibit innate HIV resistance but has been cured of it by extrinsic factors, a plausible candidate for which is the gut microbiota.

microbiology↗