Keeping herpes infection in check: Pitt researchers describe immune system strategies

October 10, 2008

Herpes 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

---

---

	The Immune System by Peter Parham (Author) The Immune System, Third Edition emphasizes the human immune system and synthesizes immunological concepts into a comprehensible, up-to-date, and reader-friendly account of how the immune system works.  Written for undergraduate, medical, veterinary, dental, and pharmacy students in immunology courses, it makes generous use of medical examples to illustrate points.  The Third Edition has been extensively revised and updated and includes two new chapters on innate and adaptive immunity, which explore the physical, cellular, and molecular principles underlying these responses to infection.  It also features enhanced coverage of aspects of innate immunity such as the complement system, Toll-like receptors, defensins, and C-reactive protein; the role of dendritic cells in...
	In Defense of Self: How the Immune System Really Works by William R. Clark (Author) We live in a sea of seething microbial predators, an infinity of invisible and invasive microorganisms capable of setting up shop inside us and sending us to an early grave. The only thing keeping them out? The immune system. William Clark's In Defense of Self offers a refreshingly accessible tour of the immune system, putting in layman's terms essential information that has been for too long the exclusive province of trained specialists. Clark explains how the immune system works by using powerful genetic, chemical, and cellular weapons to protect us from the vast majority of disease-causing microbes-bacteria, viruses, molds, and parasites. Only those microbes our bodies need to help us digest food and process vitamins are admitted. But this same system can endanger us by...
	How the Immune System Works (Blackwell's How It Works) by Lauren M. Sompayrac (Author) Understanding the immune system is crucial for both medical and bioscience students, with new research revealing yet more secrets year on year. Many books offer in-depth introductions to the subject, but How the Immune System Works remains uniquely popular for its personable and practical overview of the nuts and bolts of the immune system. This third edition provides a perfect introduction to the essential principles of the immune system, covered in humorous but highly informative 'lectures' accompanied by clear and accessible illustrations. It is perfect for exam preparation or as an enjoyable overview of a difficult subject. Both students and instructors will welcome the clarity and authority that Lauren Sompayrac brings to this timely revision.
	How the Immune System Works, Includes FREE Desktop Edition (BLACKWELL'S HOW IT WORKS SERIES) by Lauren M. Sompayrac (Author) How the Immune System Works is not a comprehensive textbook. It’s the book thousands of students have used to help them understand what’s in their big, thick, immunology texts. In this book, Dr. Sompayrac cuts through the jargon and details to reveal, in simple language, the essence of this complex subject. Fifteen easy to follow lectures, featuring the uniquely popular humorous style and engaging analogies developed by Dr Sompayrac, provide an introduction to the ‘bigger picture’, followed by practical discussion on how each of the components interacts with one another. Now featuring full-color diagrams, this book has been rigorously updated for its fourth edition to reflect today’s immunology teaching and includes updated discussion of B and T cell memory, T cell...
	90 Day Immune System Revised: This vital life-saving information will help you: Protect your body from diseases and early aging Maximize your ... and surveys Boost your vitality and b by Janet Maccaro (Author) GIVE YOURSELF 90 DAYS TO... Build and strengthen your immune system. Bring your body's system into proper balance Experience disease-free living. No matter what your health has been in the past, there is something you can do right now to give your entire body a complete makeover! Dr. Janet explains how you can improve the quality of your life with: Imagine what your life could be like with a complete immune system makeover! You best days of health are ahead of you. What are you waiting for?
	The Immune System by Peter Parham (Author) The Immune System, Second Edition has been designed for use in immunology courses for undergraduate, medical, dental, and pharmacy students. This class-tested and successful textbook synthesizes the established facts of immunology into a comprehensible, coherent, and up-to-date account of how the immune system works, rather than presenting immunology as a chronology of experiments and discoveries. Emphasizing the human immune system the text has been designed to break down the barriers which often divide basic and clinical immunology. The reader-friendly text, section and chapter summaries, and full-color illustrations make the book accessible and easily understandable to students. The Immune System is adapted from Immunobiology by Janeway, Travers & Walport.
	Digestive Wellness: Strengthen the Immune System and Prevent Disease Through Healthy Digestion, Fourth Edition by Elizabeth Lipski (Author) The definitive guide to healthy digestion! Digestive Wellness explains how your digestive system works and what to do when it doesn’t. You’ll find practical solutions to all the common gastrointestinal disorders (and many other conditions) and expert guidance on the newest advances in testing and diagnosis, nutrition, and natural therapies. Plus, you’ll learn how faulty digestion can affect the human body systemically, from migraines and skin issues to fibromyalgia and chronic fatigue syndrome. “Dr. Lipski offers a practical toolkit to support each of us—clinicians and patients—to return to wellness by bringing our gastrointestinal system back into balance and harmony. I believe that you will deeply benefit from joining Dr. Lipski on this journey toward digestive...
	Basic Immunology Updated Edition: Functions and Disorders of the Immune System With STUDENT CONSULT Online Access, 3e (Basic Immunology: Functions and Disorders of the Immune System) by Abul K. Abbas MBBS (Author), Andrew H. Lichtman MD PhD (Author) This updated 3rd edition of Basic Immunology provides a readable and concise introduction to the workings of the human immune system, with emphasis on clinical relevance. The format makes learning easy with short, easy-to-read chapters, color tables, key point summaries, and review questions in every chapter. You'll get the latest coverage on regulatory T cells, biology of the Th17 subset of CD4+ T cells, and more. The full-color artwork, comprehensive glossary, and clinical cases are just some of the features that reinforce and test your understanding of how the immune system functions. Student Consult online access lets you search the full text online and pursue further study through integration links. Covers the most up-to-date immunology information including regulatory T cells, and...
	The Immune System Cure: Optimize Your Immune System in 30 Days-The Natural Way! by Lorna Vanderheaghe (Author) What causes one person to catch a cold or flu and another to avoid it? Why do serious outbreaks of infectious diseases leave some individuals untouched? What allows someone to be incapacitated by allergies? The answer lies within nature itself-our immune system. The Immune System Cure provides simple techniques for supercharging your immune system to resist and prevent disease. Through diet, exercise, stress reduction and nutritional supplements, including plant sterols and sterolins, you can harness the power of your immune system in just 30 days and help it combat: Antibiotic-resistant bacteria Fibromyalgia Allergies Hepatitis C Tuberculosis Cancer Rheumatoid arthritis and other autoimmune diseases Chronic fatigue syndrome and more Now you can maintain a healthy...
	Super Immunity: The Essential Nutrition Guide for Boosting Your Body's Defenses to Live Longer, Stronger, and Disease Free by Joel Fuhrman (Author) Why do some of us get sick with greater frequency than others? What makes us more susceptible to illness? Are we doomed to get sick when our coworkers and family members do? Is there a secret to staying healthy? Joel Fuhrman, M.D., a leading expert and board-certified medical specialist in prevention and reversing disease, offers a comprehensive guide to superior health. Based on the latest scientific research, Super Immunity shows us how we can become almost totally resistant to colds, influenza, and other infections. The evidence is overwhelming: we can supercharge our immune system to protect our bodies against disease—everything from the common cold to cancer. Nutritional science has made phenomenal strides and discoveries in recent years, and when this new...