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Keeping herpes infection in check: Pitt researchers describe immune system strategies
October 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
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
Immune System Current Events and Immune System News RSSFirst use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
New Synthetic Molecules Trigger Immune Response to HIV and Prostate Cancer
Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in the Journal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.
Common Pain Relievers May Dilute Power of Flu Shots
With flu vaccination season in full swing, research from the University of Rochester Medical Center cautions that use of many common pain killers - Advil, Tylenol, aspirin - at the time of injection may blunt the effect of the shot and have a negative effect on the immune system.
American Dietetic Association Releases Updated Position Paper Promoting and Supporting Breastfeeding
The American Dietetic Association has released an updated position paper on breastfeeding that details health benefits for both infants and mothers and encourages promotion of breastfeeding whenever possible.
Daily dose of color may boost immunity this flu season
Hoping to keep the flu at bay? A strong immune system helps. Enjoying the bounty of colorful fruits and vegetables available right now can be an important step toward supporting your family's immune system this cold/flu season.
Immune therapy can protect against or treat later lymphoma
Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection.
PATH Malaria Vaccine Initiative shares strategy for developing 'next-generation' malaria vaccines
Marking its tenth anniversary year, the PATH Malaria Vaccine Initiative (MVI) today unveiled a new strategy that sets the stage for an aggressive push targeting the long-term goal of eliminating and eradicating malaria. Malaria is one of the world's deadliest infectious diseases, killing nearly 900,000 people a year, most of them children in sub-Saharan Africa.
Study reveals a 'missing link' in immune response to disease
The immune system's T cells have the unique responsibilities of being both jury and executioner. They examine other cells for signs of disease, including cancers or infections, and, if such evidence is found, rid them from the body. Precisely how T cells shift so swiftly from one role to another, however, has been a mystery.
Smokers with common autoimmune disorder at higher risk for skin damage
As if there weren't enough reasons to stop smoking, a team of researchers at the Research Institute of the McGill University Health Centre (RI-MUHC) have just found another.
Breakthrough in fight against Hendra virus
There has been a breakthrough in the fight against the deadly Hendra virus following the development of a treatment which shows great potential to save the lives of people who become infected with the virus.
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