23 research outputs found
Human cytomegalovirus infection of langerhans-type dendritic cells does not require the presence of the gH/gL/UL128-131A complex and is blocked after nuclear deposition of viral genomes in immature cells
Human cytomegalovirus (CMV) enters its host via the oral and genital mucosae. Langerhans-type dendritic cells (LC) are the most abundant innate immune cells at these sites, where they constitute a first line of defense against a variety of pathogens. We previously showed that immature LC (iLC) are remarkably resistant to CMV infection, while mature LC (mLC) are more permissive, particularly when exposed to clinical-strain-like strains of CMV, which display a pentameric complex consisting of the viral glycoproteins gH, gL, UL128, UL130, and UL131A on their envelope. This complex was recently shown to be required for the infection of immature monocyte-derived dendritic cells. We thus sought to establish if the presence of this complex is also necessary for virion penetration of LC and if defects in entry might be the source of iLC resistance to CMV. Here we report that the efficiency of LC infection is reduced, but not completely abolished, in the absence of the pentameric complex. While virion penetration and nuclear deposition of viral genomes are not impaired in iLC, the transcription of the viral immediate early genes UL122 and UL123 and of the delayed early gene UL50 is substantially lower than that in mLC. Together, these data show that the UL128, UL130, and UL131A proteins are dispensable for CMV entry into LC and that progression of the viral cycle in iLC is restricted at the step of viral gene expression
Agreement between self-, mother and father proxy-reports on health-related quality of life in adolescents with Tourette Syndrome
International audienceThis study aimed to investigate agreement and discrepancies between parent proxy- and adolescent self-reports on assessments of adolescentsâ health-related quality of life (HRQoL), and the role that individual factors may play in parent-adolescent agreement, in a sample of adolescents with Tourette syndrome (TS) compared to a control group of healthy adolescents. Adolescents aged 12â18 years diagnosed with TS were recruited with their parents from primary and secondary referral centres. Adolescent healthy controls were matched for gender and age. Adolescents and each of their parents completed a set of questionnaires including a HRQoL evaluation of adolescent, the âVĂ©cu et SantĂ© Perçue de lâAdolescentâ. Mother-adolescent, father-adolescent and mother-father agreements on adolescentsâ HRQoL scores were investigated at individual and group level, both in TS and control groups. Data were available for 75 adolescents, 75 mothers and 63 fathers, in the TS group. Agreement between mother, father proxy-reports and TS adolescents self-reports of HRQoL varied from poor to good, without significant difference with the control group. In TS group, mothers and fathers underestimated adolescentsâ HRQoL in âPsychological well-beingâ subscale and mothers underestimated it in âPhysical âwell-beingâ subscale, while controls overestimated adolescentsâ HRQoL in these subscales. Larger mother-adolescent discrepancies for âPsychological well-beingâ and âPhysical well-beingâ subscales were associated with internalizing symptoms. Regarding future studies, comprehensive evaluation of the various dimensions of adolescentsâ HRQoL with TS requires the integration of the perspectives of both adolescents, mothers and fathers. Clinicians should take into account this point to provide comprehensive care and services
Influence of magnesium substitution on the basic properties of hydroxyapatites
Magnesium-substituted hydroxyapatites (HAP) have been prepared to evaluate the influence of cationic substitution on the surface basic properties of HAP. Despite successful introduction of some of the magnesium cations into the HAP structure (as evidenced by XRD, infrared, and Raman), no influence of low magnesium content in Mg(x)-HAP samples (x <= 1) on the basic conversion of 2-methylbut-3-yn-1-ol was found, which can be explained by the surface content of magnesium being low, as evidenced by CO adsorption. At higher magnesium content, a higher amount of magnesium could be detected on the surface, but this resulted in a structural disorder leading to either nonstoichiometry or eventually the formation of the phase whitlockite. In this case, the associated relative decrease of the amount of basic sites, as well as the possible influence of the enhanced surface concentration of acidic POH groups, are responsible for the lower intrinsic basicity of the related samples. In contrast, preliminary results indicate that an enhancement of the basic reactivity is observed on substituting calcium for strontium
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
Efficient therapeutic options are needed to control the spread of SARS-CoV-2 that has caused more than 922,000 fatalities as of September 13th, 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block ACE2 attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Cocktails including S2M11, S2E12 or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.elocation-id: eabe3354status: Published onlin