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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.

Background: A significant proportion of the human genome is comprised of human endogenous retroviruses (HERVs). HERV transcripts are found in every human tissue. Expression of proviruses of the HERV-K(HML-2) family has been associated with development of human tumors, in particular germ cell tumors (GCT). Very little is known about transcriptional activity of individual HML-2 loci in human tissues, though.

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Despite recent success in the treatment of early-stage disease, blastic phase (BP) of chronic myeloid leukemia (CML) that is characterized by rapid expansion of therapy-refractory and differentiation-arrested blasts, remains a therapeutic challenge. The development of resistance upon continuous administration of imatinib mesylate is associated with poor prognosis pointing to the need for alternative therapeutic strategies and a better understanding of the molecular mechanisms underlying disease progression. To identify transcriptional signatures that may explain pathological characteristics and aggressive behavior of BP blasts, we performed comparative gene expression profiling on CD34 þ Ph þ cells purified from patients with untreated newly diagnosed chronic phase CML (CP, n ¼ 11) and from patients in BP (n ¼ 9) using Affymetrix oligonucleotide arrays. Supervised microarray data analysis revealed 114 differentially expressed genes (Po10 À4 ), 34 genes displaying more than two-fold transcriptional changes when comparing CP and BP groups. While 24 of these genes were downregulated, 10 genes, especially suppressor of cytokine signalling 2 (SOCS2), CAMPATH-1 antigen (CD52), and four human leukocyte antigen-related genes were strongly overexpressed in BP. Expression of selected genes was validated by real-timepolymerase chain reaction and flow cytometry. Our data suggest the existence of a common gene expression profile of CML-BP and provide new insight into the molecular phenotype of blasts associated with disease progression and high malignancy.

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Human endogenous retroviruses (HERVs) account for up to 9% of the human genome and include more than 800 elements related to betaretroviruses. While mouse mammary tumor virus (MMTV) is the accepted etiological agent of mammary tumors in mice, the role of retroviral elements in human breast cancer remains elusive. Here, we performed a comprehensive microarray-based analysis of overall retroviral transcriptional activities in 46 mammary gland tissue specimens representing pairs of nonmalignant and tumor samples from 23 patients. An analysis of nonmalignant tissue samples revealed a distinct, mammary gland-specific HERV expression profile that consists of 18 constitutively active HERV taxa. For corresponding tumor samples, a general trend toward lower levels of HERV transcription was observed, suggesting common regulatory mechanisms. In various subsets of patients, however, increased transcript levels of single class I HERV families (HERV-T, HERV-E, and HERV-F) and several class II families, including HML-6, were detected. An analysis of transcribed HML-6 sequences revealed either the activation of some or the increased activity of several proviral loci. No evidence for MMTV or human MMTV-like virus transcripts was found, indicating that transcriptionally active, MMTV analogous, exogenous viruses were not present in the breast cancer samples analyzed.Great efforts have been invested in searching for the etiology of human breast cancer, a malignancy accounting for one-fifth of all female cancers worldwide. Although many studies have identified several risk factors, such as age, diet, hormonal balance, and genetic predisposition, a clear underlying cause for the disease, especially for sporadic cases of breast cancer, remains unknown. The current data suggest that breast cancer most likely is a multifactorial disease encompassing many different causes and factors (2, 30). Moreover, it has been suggested that an infectious agent contributes to the development of human breast cancer (16,45). Of note, a novel human retrovirus (xenotropic murine leukemia virus) has recently been associated with human prostate cancer (7, 48).Since type B mouse mammary tumor virus (MMTV) is the major etiological agent of mammary gland neoplasia in laboratory mice, researchers have searched extensively for a related human retrovirus that could be responsible for human breast cancer. The existence of such a virus, although postulated for many years, has not been conclusively demonstrated, although a long line of indirect evidence for it exists. This evidence is reflected by reports on the expression of type B envelope glycoprotein (gp52) (32) and the occurrence of virus-like particles in breast cancer biopsy specimens (8), in milk (38), and in cultures of breast cancer-derived cell lines (20, 40) as well as the detection of antibodies directed against gp52 in breast cancer patients (52). However, supporting observations have been confounded by a failure to continually observe virus particles in human tumors and by numerous controversial repo...