Human Endogenous Retrovirus W Activity in Cartilage of Osteoarthritis Patients Signy Bendiksen, 1 Inigo Martinez-Zubiavrra, 2 Conny Tümmler, 3 Gunnar Knutsen, 4 Jan Elvenes, 4 Elisabeth Olsen, 3 Randi Olsen, 5 and Ugo Moens 6 ,* Abstract The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV-WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven. 5. Conclusions We have shown higher prevalence of ERVWE1 and ERVWE2 activity in chondrocytes and cartilage of OA patients compared to non-/early OA patients. However, we cannot conclude whether these viruses are innocent bystanders that are activated by pathological processes occurring during the development of OA or whether they are involved in the onset or the progression/deterioration of the disease. The high prevalence of activated ERVWEs, especially ERVWE2, may be an indicator of OA, making the detection of ERVWE transcripts a putative diagnostic marker. J Virol. 2014 Oct 1;88(19):11108-20. doi: 10.1128/JVI.01623-14. Epub 2014 Jul 23. HIV-1 Infection Leads to Increased Transcription of Human Endogenous Retrovirus HERV-K (HML-2) Proviruses In Vivo but Not to Increased Virion Production. Bhardwaj N1, Maldarelli F2, Mellors J3, Coffin JM4. Author information Abstract Recent studies suggest that human endogenous retrovirus group K (HERV-K) provirus expression plays a role in the pathogenesis of HIV-1 infection. In particular, RNA from the HML-2 subgroup of HERV-K proviruses has been reported to be highly expressed at the cellular level and detectable in the plasma of HIV-1-infected patients, suggestive of virion production and, perhaps, replication. In this study, we developed an HML-2-specific quantitative-PCR assay that detects 51 of the 89 known HML-2 proviruses in the human genome. Plasma and peripheral blood mononuclear cells (PBMCs) from HIV-negative controls and HIV-1-infected patients were collected for analysis of HML-2 RNA expression. Contrary to previous reports, we did not detect high levels of HML-2 RNA in the plasma of HIV-1-infected patients, but we did observe a significant increase of HML-2 RNA in total PBMCs compared to HIV-negative controls. The level of HML-2 expression in PBMCs does not appear to be related to patient use of antiretrovirals or to HIV-1 plasma RNA, cellular RNA, or cellular DNA levels. To investigate the source of HML-2 RNA expression, patient PBMCs were sorted into CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD14(+), and CD3(-) CD20(+) cell subsets and then analyzed for HML-2 RNA levels. No single cell subset was enriched for HML-2 RNA expression in HIV-1-infected patients, but there appears to be substantial variability in the level of HML-2 expression depending on the cell type. IMPORTANCE: Here, we report that human endogenous retrovirus group K (HERV-K) (HML-2) proviruses are expressed at significantly higher levels in peripheral blood mononuclear cells (PBMCs) from patients with HIV-1 infection than in those from uninfected individuals. However, contrary to previous reports, this expression did not lead to detectable virions in the plasma of these patients. In addition, we found that HML-2 proviruses were expressed in multiple blood cell types from HIV-1-infected individuals, and the magnitude of HML-2 expression was not related to HIV-1 disease markers in this patient cohort. These findings may have implications for HML-2-based therapies targeting HIV-1 infection. J Gen Virol. 2014 Sep 12. pii: vir.0.070631-0. doi: 10.1099/vir.0.070631-0. [Epub ahead of print] Recent developments linking retroviruses to human breast cancer: infectious agent, enemy within or both? Salmons B1, Lawson JS2, Gunzburg WH3. Author information Abstract Evidence is accumulating that one or more beta-retrovirus is associated with human breast cancer. Retroviruses can exist as an infectious (exogenous) virus or as a part of the genetic information of cells due to germline integration (endogenous). An exogenous virus with a genome that is highly homologous to mouse mammary tumor virus (MMTV) is gaining acceptance as possibly being associated with human breast cancer and recently furnished evidence is discussed in this article, as is the evidence for involvement of an endogenous human beta-retrovirus, HERV-K. Modes of interaction are also reviewed and linkage to APOBEC3 suggested. Copyright © 2014, the Society for General Microbiology. Eco ERV activation aboard but why? Over active immune system? Is it causing a wide-spread disregulation and expression of ERV RNA/DNA/proteins?