Marie-Lise Blondot

• PhD
• PostDoc Position at University of Bordeaux

The vasculature is heavily impacted by SARS-CoV-2 infection. Conflicting results exist about the mechanisms by which SARS-CoV-2 virus acts on the vasculature. The presence of the virus within endothelial cells has been reported in patients’ samples. However, the ACE2 receptor is not detected in endothelial cells when analyzed by RNAseq analysis. Th...

The vasculature is heavily impacted by SARS-CoV-2 infection. Conflicting results exist concerningthe mechanisms by which the SARS-CoV-2 virus acts on the vasculature. The presence of the virus within endothelial cells has been reported in patient samples. However, the ACE2 receptor wasnot detected in endothelial cells when analyzed by RNAseq analys...

SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two i...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract, where infections can cause an acute respiratory distress syndrome with a high degree of mortality in elderly patients. We used reconstituted primary bronchial epit...

Hepatitis B virus infections are the main reason for hepatocellular carcinoma development. Current treatment reduces the viral load but rarely leads to virus elimination. Despite its medical importance, little is known about infection dynamics on the cellular level not at least due to technical obstacles. Regardless of infections leading to extreme...

Background: HIV infects around one hundred thousand patients in the Republic of the Congo. Approximately 25% of them receive an antiretroviral treatment; current first-line regimens include two NRTIs and one NNRTI, reverse transcriptase inhibitors. Recently, protease inhibitors (PIs) were also introduced as second-line therapy upon clinical signs o...

Since the beginning of the pandemic, a race has been underway to detect SARS-CoV-2 virus infection (PCR screening, serological diagnostic kits), treat patients (drug repurposing, standard care) and develop a vaccine. After almost a year of active circulation worldwide, SARS-CoV-2 variants have appeared in different countries. Those variants include...

The beta-coronavirus SARS-CoV-2 is at the origin of a persistent worldwide pandemic. SARS-CoV-2 infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract eventually causing acute severe respiratory syndrome with a high degree of mortality in the elderly. Here we use reconstituted pr...

Background & aims: Hepatitis B virus (HBV) has a DNA genome but replicates within nucleus by transcription of an RNA pregenome, which is converted to DNA in cytoplasmic capsids. Capsids in this compartment are correlated with inflammation and epitopes of the capsid protein core (Cp) are the main target for T cell-mediated immune response. We inves...

Significance Human immunodeficiency viruses (HIV) have developed strategies to interfere with DNA repair in host cells. Some DNA repair pathways represent restriction mechanisms that counteract the virus as soon as it penetrates into the host cell, before the establishment of an interferon response. Here we identify helicase-like transcription fact...

Hepatitis B virus (HBV) replicates its genomic information in the nucleus via transcription and therefore has to deliver its partially double stranded DNA genome into the nucleus. Like other viruses with a nuclear replication phase, HBV genomes are transported inside the viral capsids first through the cytoplasm towards the nuclear envelope. Follow...

Vpr is one of the most enigmatic viral auxiliary proteins of HIV. During the past twenty years, several activities have been ascribed to this viral protein, but one, its ability to mediate cell cycle arrest at the G2 to M transition has been the most extensively studied. Nonetheless, the genuine role of Vpr and its pathophysiological relevance in t...

Significance Human respiratory syncytial virus (HRSV) is the leading cause of lower respiratory tract illness in young children; however, no vaccine exists and current immunoprophylaxis regimes are both expensive and incompletely protective. We report the crystal structure of the HRSV M2-1 transcription factor that is essential for virus gene expre...

Binding of yeast RNA to 15N-M2-158–177 followed by 1H-15N HSQC spectra. Measurements were done at 298K and a field of 14.1 T. The reference spectrum of 15N-M2-158–177 (50 µM) is shown in black, the spectrum after addition of 4 mg/mL yeast RNA (∼1∶1 molar ratio) in red and after treatment by RNAse A in green. (EPS)

Intensity variations of M2-158–177 HSQC spectra in the presence of phosphoprotein. (A) Superposition of 1H-15N HSQC spectra of 15N13C-labeled M2-158–177 without (black) and with 0.5 equivalent of full-length RSV phosphoprotein P (blue) shows overall line broadening on addition of P. (B) Arginine 13Cδ-1Hδ and lysine 13Cε-1Hε region of 1H-13C HSQC sp...

Determination of apparent RNA dissociations constants by titration experiments with 1H-15N HSQC experiments of 15N-M2-158–177. 1H and 15N chemical shift differences of backbone amides or Q93 side chain (denoted H, N, Hε21, Hε22, and Nε2 respectively) are displayed versus the ratio of RNA concentration relative to protein for chosen residues showing...

Sequence alignment of M2-1 and VP30 proteins. (A) Alignment of primary sequences of M2-1 proteins of human Respiratory Syncytial Virus (hRSV, strain Long, UniProt accession number P28887.1), bovine RSV (bRSV, strain ATue51908, NC_001989.1), Pneumonia virus of mouse (PVM, YP_173333), human Metapneumovirus (HMPV, AAM12941.1), and avian Metapneumoviru...

1H-15N chemical shift perturbations measured for 15N-M2-158–177 in the presence of RNA. 1H-15N HSQC spectra were recorded at 14.1 T and 293 K with 50 or 60 µM protein. Per-residue plots of combined 1H/15N chemical shifts in absolute values are represented for (a) Yeast RNA (Roche) (4 mg/mL), for (b) an RSV unrelated hairpin UGA2 hairpin (20∶1 RNA∶p...

Changes in 1H-15N HSQC spectra of M2-158–177 single mutants K92D, R126D, T130D, L148A, K150D, R151D and T160D and N163D. K92D, K150D and R151D strongly reduced in vitro RNA binding to M2-1 whereas R126D, T130D, L148A, T160D and N163D were excluded from cytoplasmic inclusion bodies containing RSV phosphoprotein. All resulted in a nearly total loss o...

NMR structure statistics of RSV M2-158–177. (DOC)

ITC binding isotherms for P binding to M2-158–177. (A) Raw binding data obtained for 20 automatic injections of M2-158–177 (2 µl for each injection, 335 µM protein concentration) into a cell containing P (200 µL initial volume; 33 µM initial protein concentration). Proteins were suspended in 1× PBS. (B) Integrated titration curve obtained from the...

Supplemental Materials and Methods. (DOC)

Respiratory syncytial virus (RSV) protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp) complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties a...

The respiratory syncytial virus (RSV) Large protein L is the catalytic subunit of the RNA-dependent RNA polymerase complex. Currently, no structural information is available for RSV L. Sequence alignments of L protein from human and bovine strains of RSV revealed the existence of two variable regions, VR1 and VR2. Following comparison with morbilli...

M2-1 is an essential co-factor of the respiratory syncytial virus, an important respiratory pathogen in infants and calves. It acts as a transcription antitermination factor which enhances the processivity of the polymerase. Within the polymerase complex, M2-1 interacts with a second co-factor, the phosphoprotein P. It has been shown previously tha...

To determine human herpesvirus 8 (HHV-8) K1 genotypes in patients with Kaposi sarcoma (KS) from Peru, we characterized HHV-8 in 25 KS biopsy samples. Our findings of 8 A, 1 B, 14 C, and 2 E subtypes showed high HHV-8 diversity in these patients and association between E genotype and KS development.