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Archive - May 11, 2017

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Scientists ID Human Protein Essential for Human Cytomegalovirus Replication

Scientists have demonstrated that a human protein known as valosin containing protein (VCP) is essential for replication of human cytomegalovirus (HCMV). The findings, published in the open-access journal PLOS Pathogens, identify VCP as a potential new treatment target. The article is titled “The Host Ubiquitin-Dependent Segregase VCP/p97 Is Required for the Onset of Human Cytomegalovirus Replication.” HCMV infects 30 to 100 percent of people worldwide, depending on socioeconomic status. While most remain symptom-free, HCMV can be dangerous or deadly for people with weakened immune systems or for babies infected before birth. Some HCMV treatments exist, but their benefits are limited, and scientists are investigating new ways to treat and prevent infection. To better understand how HCMV replicates during active infection, Dr. Yao-Tang Lin and colleagues at the University of Edinburgh, U.K., performed a search for human genes needed by the virus for replication. They found that reducing the expression of the VCP gene in HCMV-infected human cells significantly reduced viral replication in the cells. Additional experiments showed that, without VCP, HCMV is unable to express a critical gene known as IE2. This viral gene is known to be essential for replication and is thought to play a major role when the virus switches from symptom-free, dormant infection to active infection. Given the critical importance of VCP for HCMV replication, the scientists tested the effects of a chemical known to inhibit the activity of VCP. They found that the inhibitor, known as NMS-873, reduced HCMV replication and IE2 expression in infected cells. NMS-873 appeared to be ten times more potent than Ganciclovir, the most commonly used antiviral treatment for HCMV.

Study Shows Age-Associated B Cells (ABCs) Drive Autoimmune Disease

Researchers at National Jewish Health have identified a trigger for autoimmune diseases such as lupus, Crohn's disease and multiple sclerosis. The findings, published in the April 2017 issue of the Journal of Clinical Investigation, help explain why women suffer autoimmune disease more frequently than men, and suggest a therapeutic target to prevent autoimmune disease in humans. The open-access article is titled “B cells Expressing the Transcription Factor T-Bet Drive Lupus-Like Autoimmunity.” "Our findings confirm that age-associated B cells (ABCs) drive autoimmune disease," said Kira Rubtsova, PhD, an instructor in biomedical science at National Jewish Health. "We demonstrated that the transcription factor T-bet inside B cells causes ABCs to develop. When we deleted T-bet inside B cells, mice prone to develop autoimmune disease remained healthy. We believe the same process occurs in humans with autoimmune disease, more often in elderly women." Autoimmune diseases occur when the immune system attacks and destroys the organs and tissue of its own host. Dozens of autoimmune diseases afflict millions of people in the United States. Several autoimmune diseases, including lupus, rheumatoid arthritis and multiple sclerosis strike women 2 times to 10 times as often as men. Overall, about 80 percent of autoimmune patients are women. There is no cure for autoimmune disease. B cells are important players in autoimmune disease. The National Jewish Health research team, led by Chair of Biomedical Science Philippa Marrack, PhD, previously identified a subset of B cells that accumulate in autoimmune patients, and in autoimmune and elderly female mice.

Gene Sequencing Study Reveals Unusual Mutations in Endometriosis

Using gene sequencing tools, scientists from Johns Hopkins Medicine and the University of British Columbia have found a set of genetic mutations in samples from 24 women with benign endometriosis, a painful disorder marked by the growth of uterine tissue outside of the womb. The findings, described in the May 11, 2017 issue of the New England Journal of Medicine, may eventually help scientists develop molecular tests to distinguish between aggressive and clinically "indolent," or non-aggressive, types of endometriosis. The NEJM article is titled “Cancer-Associated Mutations in Endometriosis without Cancer.” "Our discovery of these mutations is a first step in developing a genetics-based system for classifying endometriosis so that clinicians can sort out which forms of the disorder may need more aggressive treatment and which may not," says Ie-Ming Shih, MD, PhD, the Richard W. TeLinde Distinguished Professor in the Department of Gynecology & Obstetrics at the Johns Hopkins University School of Medicine and Co-Director of the Breast and Ovarian Cancer Program at the Johns Hopkins Kimmel Cancer Center. Endometriosis occurs when tissue lining the uterus forms and grows outside of the organ, most often into the abdomen. The disease occurs in up to 10 percent of women before menopause and half of those with abdominal pain and infertility problems. In the 1920s, Johns Hopkins graduate and trained gynecologist John Sampson first coined the term "endometriosis" and proposed the idea that endometriosis resulted when normal endometrial tissue spilled out through the fallopian tubes into the abdominal cavity during menstruation. The new study, Dr. Shih says, challenges that view.