Histone deacetylases in viral infections

Chromatin remodeling and gene expression are regulated by histone deacetylases (HDACs) that condense the chromatin structure by deacetylating histones. HDACs comprise a group of enzymes that are responsible for the regulation of both cellular and viral genes at the transcriptional level. In mammals, a total of 18 HDACs have been identified and grouped into four classes, i.e., class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10), class III (Sirt1–Sirt7), and class IV (HDAC11). We review here the role of HDACs on viral replication and how HDAC inhibitors could potentially be used as new therapeutic tools in several viral infections

Severe acute pancreatitis related to the use of adefovir in a liver transplant recipient.

International audienc

The MEDICALIP Project: Toward the screening of the cytomegalovirus

International audienceince rubella vaccine was established, cytomegalovirus infection has become the most frequent cause of congenital infections. The French Health Authority is urging a diagnosis at birth for newborns. Since no screening device is commercially available, a consortium has been established to set-up an original device. The project has been funded by the French National Research Agency. The device consists of a disposable cartridge containing the biological sample and the reactive liquids required for immuno-fluorescencence detection on a functionalized surface. It also consists of a mobile reader used to drive the fluids onto the biosensor and to ensure the optical measurement. Positive and negative samples can be discriminated with a fluorescence intensity ratio of 3

A mobile device for screening the cytomegalovirus at the newborn's bed

International audienceSince rubella vaccine was established, cytomegalovirus (CMV) infection has become the most frequent cause of congenital infections. Before deciding of the benefit of screening in this populations, the French Health Authority (HAS) is urging a diagnosis at birth for newborns. Since no screening device is commercially available, a consortium has been established to set-up an original device. The consortium consists of 3 academic institutions and 2 private companies, and the study has been funded by the French National Research Agency. The device consists of a disposable cartridge containing the biological sample and the reactive liquids required for immunofluorescencence detection on a functionalized surface. It also consists of a mobile reader used to drive the fluids onto the biosensor and to ensure the optical measurement. Up to now, positive and negative samples can be discriminated with a fluorescence intensity ratio of 3

DETECTING CYTOMEGALOVIRUS IN BREASTMILK: Towards a device for self-monitoring risks of postnatal infection

International audienceHuman cytomegalovirus (HCMV) infection is a major cause of morbidity worldwide especially in newborn infants. While congenital HCMV infection affects 2-5% of preterm newborns, the risk of postnatal infection particularly through breast milk is higher in this population (prevalence about 20%) since more than one mother on two is affected. Congenital and postnatal infection can lead to important clinical complications such as deafness, learning disabilities, and mental retardation during childhood. Neonatologists are squeezed in their clinical practice: either breastfeeding is favored without any milk treatment going on exposure of preterm infants to a potential infection, or milk is systematically treated by freezing or pasteurization but with deprivation of non-at-risk infants from the benefits of fresh milk. In this position paper, we propose a possible solution to differentiate milk with risk of HCMV contamination from milk without any risk. This would allow subsequent adaptation of the milk feeding strategy. Also, because the HCMV contamination peak appears 4 to 8 weeks after birth, the work we present here should lead to a device meant to be used both at hospital and at home in a self-testing manner

Maribavir use in practice for cytomegalovirus infection in French transplantation centers.

International audienceMaribavir (MBV), a UL97 inhibitor, shows good oral bioavailability, low host cell toxicity, and theoretical benefits to inhibit cross-resistant viruses. We herein examined clinical and virological outcomes of 12 patients, including 3 bone marrow recipients and 9 organ recipients infected with resistant cytomegalovirus (CMV) and treated with MBV during 2011-2012. All received at least 800-mg daily doses. They had developed clinical (12/12) and/or virological (11/12) resistance to CMV infection. Based on a decrease of viral load in blood >1.5 log copies/mL half of them responded to MBV treatment. The individual changes varied from a rapid decrease in viral load (n = 4) to no response (n = 3) with some late response slowly decreasing viremia (n = 3). In 2 cases MBV was used as secondary prophylaxis. No clear parameter emerged as a clinical surrogate for nonresponse to MBV. These results contrast with the lack of efficacy in phase III trials of MBV prophylaxis among stem cell recipients, which were possibly due to low doses or inadequate timing of drug initiation in the study. Additional clinical and surrogate laboratory markers are needed to determine antiviral responses to guide MBV use. Dosage ranging studies might benefit future MBV use