Keeping herpes infection in check: Pitt researchers describe immune system strategiesOctober 10, 2008Herpes simplex virus type I can cause bouts of cold sores, blindness and potentially lethal encephalitis when it reawakens from a quiescent state in the nerve cells it infects. To prevent these consequences, the stealthy virus is kept under constant guard by the immune system, say University of Pittsburgh scientists. Their research challenges the once common notion that latent HSV-1 in sensory neurons is invisible to the immune system. Actually, immune cells keep the infection under close surveillance, actively holding HSV-1 in check without destroying the neurons harboring it, said Robert L. Hendricks, Ph.D., Joseph F. Novak professor and vice-chair for research in the Department of Ophthalmology and professor in the Departments of Immunology and Microbiology and Molecular Genetics at the University of Pittsburgh School of Medicine. Sensory neurons may not regenerate, so an immune system attack that destroys them could do more harm than good.
In a paper published in the October 10 issue of Science, teams led by Dr. Hendricks and Paul R. Kinchington, Ph.D., also a professor in the University of Pittsburgh School of Medicine Department of Ophthalmology, show one way this balancing act is carried out. Immune cells called CD8 T cells attack virus-infected cells with lytic granules, which are packets of potentially toxic enzymes. Transport of lytic granule contents into infected cells typically initiates a process that leads to a form of cellular suicide called apoptosis. However, according to the researchers' experiments, that isn't the case when CD8 T cells target infected sensory neurons. "Instead, the lytic granules attack the viral infection in neurons without killing them," explained Dr. Hendricks, senior author. "One way is through a lytic granule enzyme called granzyme B, which cleaves an important HSV-1 protein required for viral replication. That means the neuron and the virus survive, but the infection can't spread to other cells." Recurrences of cold sores, eye disease and other forms of herpetic lesions occur if the balance shifts and the virus can bypass surveillance by the immune system. Dr. Hendricks noted that up to 90 percent of people eventually become infected with HSV-1, many in childhood. The initial infection typically produces mild symptoms or none at all, but the virus remains in the neurons for a lifetime, occasionally waking up to cause disease. It repeatedly scars the cornea when this occurs in the eye, making HSV-1 a leading infectious cause of blindness. Previous studies showed CD8 T cells can use interferon-gamma to block reactivation without killing the neuron, but only some sets of neurons are controlled in this manner, Dr. Hendricks said. His team will continue to try to identify how immune cells, HSV-1 and neurons interact, which could have implications for treatment and vaccine development for HSV-1 infections, as well as for gene therapy applications that use harmless versions of the herpes virus as a vector to ferry treatment genes into cells. University of Pittsburgh Schools of the Health Sciences | |||||||||||||||||||||
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Related Immune System Current Events and Immune System News Articles Evolution in action: Our antibodies take 'evolutionary leaps' to fight microbes With cold and flu season in full swing, the fact that viruses and bacteria rapidly evolve is apparent with every sneeze, sniffle, and cough. A new report in the January 2009 issue of The FASEB Journal, explains for the first time how humans keep up with microbes by rearranging the genes that make antibodies to foreign invaders. This research fills a significant gap in our understanding of how the immune system helps us survive. Understanding Extinct Microbes May Influence the State of Modern Human Health The study of ancient microbes may not seem consequential, but such pioneering research at the University of Oklahoma has implications for the state of modern human health. Cecil Lewis, assistant professor in the Department of Anthropology, says results of this research raise questions about the microbes living on and within people. Lung cancer cells activate inflammation to induce metastasis A research team from the University of California, San Diego School of Medicine has identified a protein produced by cancerous lung epithelial cells that enhances metastasis by stimulating the activity of inflammatory cells. Researchers engineer pancreatic cell transplants to evade immune response In a finding that could significantly influence the way type 1 diabetes is treated, researchers at Albert Einstein College of Medicine of Yeshiva University have developed a technique for transplanting insulin-producing pancreatic cells that causes only a minimal immune response in recipients. Salk researchers develop novel glioblastoma mouse model Researchers at the Salk Institute for Biological Studies have developed a versatile mouse model of glioblastoma-the most common and deadly brain cancer in humans-that closely resembles the development and progression of human brain tumors that arise naturally. Immune cells contribute to the development of Parkinson's disease Parkinson disease is a neurodegenerative disorder that impairs movement, balance, speech, and other functions. It is characterized by the loss of nerves in the brain that produce a substance known as dopamine. Redesigned protein accelerates blood clotting Researchers have made several, subtle changes in the structure of a key protein, dramatically increasing its ability to drive blood clotting, according to a study published in a December edition of the Journal of Thrombosis and Haemostasis. Biomedical researchers create artificial human bone marrow in a test tube Artificial bone marrow that can continuously make red and white blood cells has been created in a University of Michigan lab. Peering inside the skull of a mouse to solve meningitis mystery NYU Langone Medical Center scientists and their collaborators at the Scripps Research Institute in La Jolla, Calif., have discovered an unexpected cause for the fatal seizures seen in mice with viral meningitis, an infection of the central nervous system, according to a study published in the journal Nature. Breathing life into injured lungs: World-first technique will expand lung donor organ pool For the first time in the world, transplant surgeons at Toronto General Hospital, University Health Network used a new technique to repair an injured donor lung that was unsuitable for transplant, and then successfully transplanted it into a patient. More Immune System Current Events and Immune System News Articles |
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