Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.: HERV-W in schizophrenia and bipolar disorder

International audienceEpidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of severe psychotic disorders

The DNA copy number of human endogenous retrovirus-W (MSRV-type) is increased in multiple sclerosis patients and is influenced by gender and disease severity.

BACKGROUND: Multiple sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV) is a member of type-W endogenous retrovirus family (HERV-W), known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls. RESULTS: 178 MS patients (62.9% women) and 124 controls (56.5% women) were included. MSRV env load (copies/pg of DNA) was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs). MSRV load was more elevated in MS patients than in controls (p = 4.15e-7). MS women presented higher MSRV load than control women (p = 0.009) and MS men also had higher load than control men (p = 2.77e-6). Besides, women had higher levels than men, both among patients (p = 0.007) and controls (p = 1.24e-6). Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively). CONCLUSIONS: MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS

MSRV load and clinical evolution in women with MS.

<p><b>A)</b> The EDSS Score is higher among patients with a MSRV DNA load above the Cut-Off* (Cut-Off = 2.22, corresponding to 165 copies/pg of DNA) (n = 7) than below (n = 101). ANOVA; p = 0.032. <b>B)</b> MSSS score is higher among patients with a MSRV DNA load above the Cut-Off*(n = 7) than below (n = 99). ANOVA; p = 0.044. Points represent the mean and bars represent 95% Confidence Interval of Mean. MSRV load represents MSRV copies/pg of DNA. *Cut-Off = Mean _log10_{MSRV DNA}_Controls +2*S.D _{log10 MSRV DNA}_Controls; This represents the threshold above which the values are no longer within the range of the normal population.</p

MSRV DNA load MS diagnosis and sex.

<p><b>A)</b> MSRV DNA load is more elevated in PBMC of MS patients (n = 178) than in controls (n = 124) (ANOVA; p = 4.15e-7). B<b>)</b> MSRV DNA load is more elevated in MS women (n = 112) than in control women (n = 70) (ANOVA; p = 0.009), control men (n = 54) (ANOVA; p = 8.87e-14) and MS men (n = 66) (ANOVA; p = 0.007). MSRV DNA load is more elevated in control women (n = 70) than in control men (n = 54) (ANOVA; p = 1.24e-6). Points represent the mean and bars represent 95% Confidence Interval of Mean. MSRV DNA load represents MSRV copies/pg of DNA.</p

Financiarisation et travail

Le “Corpus” de ce numéro de La Nouvelle Revue du Travail est consacré aux interdépendances entre la financiarisation de l’économie et les transformations contemporaines du travail. L’entrée privilégiée ici est la gestion, ses acteurs et ses dispositifs, instances intermédiaires grâce auxquelles le macro-économique conforme le microsocial, à travers les métamorphoses imprimées au travail. C’est en particulier autour de l’étude critique des actes désormais omniprésents de mesures physiques et de valorisations comptables des activités de travail conduits par les managers (ou les gestionnaires) que s’est construit ce numéro. Dit autrement, les articles ici rassemblés cherchent à éclairer les différentes manières dont les impératifs de rentabilité financière sont réinterprétés en termes de décisions de rationalisation du travail et marquent les organisations contemporaines – qu’elles soient publiques ou privées – du même réductionnisme calculatoire, sans oublier les réactions ou les résistances des personnels concernés. Procéder à un tel choix, c’est renouer avec une ambition initiale de la sociologie, quand Durkheim et les membres de L’Année sociologique discutaient les impensés anthropologiques de l’économie politique, ou quand Weber, Sombart ou Marx nous invitaient à nous intéresser à la comptabilité pour comprendre comment le capitalisme entraînait le travail dans les voies qui étaient les siennes