Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders

Abstract

The detection and identification of retroviral transcripts in brain samples, cerebrospinal fluid, and plasma of individuals with recent-onset schizophrenia and schizoaffective disorders suggest that activation or upregulation of distinct human endogenous retroviruses (HERVs) may play a role in the etiopathogenesis of neuropsychiatric diseases. To test this hypothesis, we performed a comprehensive microarray-based analysis of HERV transcriptional activity in human brains. We investigated 50 representative members of 20 HERV families in a total of 215 brain samples derived from individuals with schizophrenia or bipolar disorders and matched controls. A characteristic brain-specific retroviral activity profile was found that consists of members of the class I families HERV-E, HERV-F, and ERV9 and members of HERV-K taxa. In addition to these constitutively expressed HERVs, a number of differentially active HERV elements were identified in all brain samples independent of the disease pattern that may reflect differences in the genetic background of the tested individuals. Only a subgroup of the HML-2 family (HERV-K10) was significantly overrepresented in both bipolar-disorder-and schizophrenia-associated samples compared to healthy brains, suggesting a potential association with disease. Real-time PCR analysis of HERV env transcripts with coding capacity potentially involved in neuroinflammatory conditions revealed that env expression of HERV-W, HERV-FRD, and HML-2 remains unaffected regardless of the clinical picture. Our data suggest that HERV transcription in brains is weakly correlated with schizophrenia and related diseases but may be influenced by the individual genetic background, brain-infiltrating immune cells, or medical treatment.

Neuroinflammation in bipolar disorders

“…This was due to the fact that our search strategy was over-inclusive to avoid missing any suitable article. [24] Germany [28] Neuroinflammatory microglia activation is compatible with these data; the influence of medication has not been ruled out *S100β induces the expression of IL-1β in cultured ratmicroglia; [37,38] astrocyte synthesis of S100β in AD may be triggered by microglial-derived IL-1. [39] BA: brodmann's area; TNFR2: tumor necrosis factor receptor, type 2; IL-1β: interleukin-1 beta; MIP 1α/LD78: macrophage inflammatory protein-1 alpha/LD78; PrP c : cellular prion protein; QRT-PCR: quantitative real-time polymerase chain reaction; MyD88: myeloid differentiation factor 88; NF-κB: nuclear factor kappa B; GFAP: glial fibrillary acidic protein; iNOS: inducible nitric oxide synthase; NMDA: N-methyl-D-aspartic acid; HERV: human endogenous retrovirus; HERV-W: human endogenous retrovirus-W; AA: arachidonic acid; cPLA2: cytosolic phospholipase A2; sPLA2-IIA: secretory phospholipase A2-IIA; COX: cyclooxygenase; mPGES: membrane prostaglandin E synthase; cPGES: cytosolic prostaglandin E synthase; TNF-α: tumor necrosis factor α It proved to be more tiresome to download all papers, but this allowed us to identify two papers that would otherwise have gone undetected.…”

Variable Transcriptional Activity of Endogenous Retroviruses in Human Breast Cancer

“…Furthermore, tissue-specific HERV expression profiles could be established for all human tissues investigated so far, confirming that HERVs are permanent components of the human transcriptome (13,42). In a few studies, a prevalence of HERV transcripts, in particular class II elements, such as members of the HML-2 family, was reported for breast cancer tissues and cell lines (5,50,51).…”

Les rétrovirus endogènes humains, une implication dans la schizophrénie et le trouble bipolaire

“…différence en ce qui concerne les HERV-W [21]. D'autres auteurs ont mis en évidence (1) une augmentation de 45 % de la transcription de HERV-W pol dans le cortex frontal des patients SCZ ; (2) une augmentation de l'activité transcriptase inverse dans le cervelet de ces patients ; et (3) une augmentation de la transcription de HERVK10 dans le cortex frontal des patients présentant un TB [22].…”