Biology subjects

Boutolleau, D.

Publications and source records attributed to Boutolleau, D..

6 recordsLinked to original sources

bioRxiv2025

LAVR-289, a new acyclo-nucleoside phosphonate having broad-spectrum activity against herpesviruses.

Human herpesviruses are latent opportunistic large dsDNA viruses that can have deleterious effect in immunocompromised patients by triggering life-threatening infections. Over the past years, different antivirals have been developed against a variety of herpesviruses, including Acyclovir for herpes simplex viruses (HSV1 and 2) and ganciclovir and letermovir for human cytomegalovirus (hCMV). However, broad-spectrum inhibitors of herpesvirus infections are still missing. Here we report the efficacy of LAVR-289, a new acyclic nucleoside analog, on a broad variety of herpesviruses from human and animal origin. LAVR-289 displays nanomolar efficiency in vitro, is active on viral strains resistant to gold standard antivirals and ex vivo on reconstituted human skin infected with HSV1. Combined with its anti-poxvirus and anti-adenovirus activity, LAVR-289 can become the next gold standard for the management of opportunistic virus infections in immunocompromised patient.

microbiology↗

bioRxiv2024

What challenges remain in harmonizing cytomegalovirus viral load quantification across laboratories?

Cytomegalovirus (CMV) infection monitoring is a key element in the management of immunocompromised patients. CMV DNA quantification in plasma or whole blood is the best indicator for clinicians to adjust immunosuppressive or antiviral therapies. Despite the availability of internationally standardized material, the commutability of CMV quantification results across laboratories remains inadequate. To assess inter-laboratory variability in CMV DNA quantification, we conducted a blinded study in seven independent laboratories. Each participant received a panel of 92 specimens for CMV quantification using their routinely used standard platform. While quantifications were highly correlated and reproducible, large discrepancies were observed with differences up to 1.45 log10 IU/mL between techniques for identical specimens. However, quantification scattering was lower for the WHO international standard or a commercially tested control (IQR=0.129) than for clinical specimens (0.469; p=0.0142). Blind quantification of the WHO or the commercial standard indicated that all techniques, except for fully integrated platforms, did not align well with the expected values and most platforms tended to quantify specimens and standards differently. Recalibration of all platforms against the same standard improved the spread of results, but differences of up to 1.19 log10 IU/mL remained for the same specimens. Achieving commutability in CMV quantification remains an elusive goal. Efforts should focus on improving both the assay calibrators and the run controls, which currently do not appear to simulate the unique characteristics of circulating CMV in patients. Until this is resolved, each transplanted patient should be consistently monitored by the same laboratory on the same platform.

microbiology↗

bioRxiv2022

Phylogeographic analysis reveals an ancient East African origin of the human herpes simplexvirus 2 dispersal out-of-Africa.

Human herpes simplex virus 2 (HSV-2) is a globally ubiquitous, slow evolving DNA virus. HSV-2 genomic diversity can be divided into two main groups: an African lineage and worldwide lineage. Competing hypotheses have been put forth to explain the history of HSV-2. HSV-2 may have originated in Africa and then followed the first wave of human migration out of Africa between 50-100 kya. Alternatively, HSV-2 may have migrated out of Africa via the trans-Atlantic slave trade within the last 150-500 years. The lack of HSV-2 genomes from West and Central Africa, combined with a lack of molecular clock signal in HSV-2 has precluded robust testing of these competing hypotheses. Here, we expand the geographic sampling of HSV-2 genomes in order to resolve the geography and timing of divergence events within HSV-2. We analyze 65 newly sequenced HSV-2 genomes collected from primarily West and Central Africa along with 330 previously published genomes sampled over a 47-year period. Evolutionary simulations confirm that the molecular clock in HSV-2 is too slow to be detected using available data. However, phylogeographic analysis indicates that all biologically plausible evolutionary rates would place the ancestor of the worldwide lineage in East Africa, arguing against the trans-Atlantic slave trade as the source of worldwide diversity. The best supported evolutionary rates between 4.2x10-8 and 5.6x10-8 substitutions/site/year suggest a most recent common ancestor for HSV-2 around 90-120 kya and initial dispersal around 21.9-29.3 kya. These dates suggest HSV-2 left Africa during subsequent waves of human migration out of East Africa.

evolutionary biology↗

bioRxiv2021

Neutralization heterogeneity of United Kingdom and South-African SARS CoV-2 variants in BNT162b2-vaccinated or convalescent COVID-19 healthcare workers

There are concerns about neutralizing antibodies (NAb) potency against the newly emerged VOC202012/01 (UK) and 501Y.V2 (SA) SARS-CoV-2 variants in mRNA-vaccinated subjects and in recovered COVID-19 patients. We used a viral neutralization test with a strict 100% neutralizing criterion on UK and SA clinical isolates in comparison with a globally distributed D614G SARS-CoV-2 strain. In two doses BNT162b2-vaccinated healthcare workers (HCW), despite heterogeneity in neutralizing capacity against the three SARS-CoV-2 strains, most of the sera harbored at least a NAb titer [≥] 1:10 suggesting a certain humoral protection activity either on UK or SA variants. However, six months after mild forms of COVID-19, an important proportion of HCW displayed no neutralizing activity against SA strain. This result supports strong recommendations for vaccination of previously infected subjects.

microbiology↗

bioRxiv2020

Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2

BackgroundRT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas(R) (Roche) and the RealStar(R) assay (Altona). MethodsAssessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas(R) assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMerieux). ResultsOverall, the agreement (positive for at least one gene) was 76%. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99%. Regarding the positive Ct values, linear regression analysis showed a determination correlation (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas(R) minus RealStar(R)) was + 3.3 Ct, with a SD of + 2.3 Ct. ConclusionsIn this comparison, both RealStar(R) and Cobas(R) assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar(R) assay, probably due to a low viral load close to the detection limit of both assays.

microbiology↗

bioRxiv2016

Ancient recombination events between human herpes simplex viruses

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are seen as close relatives but also unambiguously considered as evolutionary independent units. Here, we sequenced the genomes of 18 HSV-2 isolates characterized by divergent UL30 gene sequences to further elucidate the evolutionary history of this virus. Surprisingly, genome-wide recombination analyses showed that all HSV-2 genomes sequenced to date comprise HSV-1 fragments. Using phylogenomic analyses, we could also show that two main HSV-2 lineages exist. One lineage is mostly restricted to sub-Saharan Africa while the other has reached a global distribution. Interestingly, only the worldwide lineage is characterized by ancient recombination events with HSV-1. Our findings highlight the complexity of HSV-2 evolution, a virus of likely zoonotic origin which later recombined with its human-adapted relative. They also suggest that co-infections with HSV-1 and 2 may have genomic and potentially functional consequences and should therefore be monitored more closely.

microbiology↗