October 26, 2009

The viruses that cause cold sores, chickenpox, and shingles require a host cell protein complex to initiate infection, but certain antidepressants appear to disrupt the activity of that complex and potentially prevent infection, according to scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

In a study now online in Nature Medicine, a research group led by Thomas M. Kristie, Ph.D., chief of the Molecular Genetics Section in the NIAID Laboratory of Viral Diseases, found that the host enzyme LSD1 interacts with a key host protein (HCF-1) that the herpesviruses require to infect host cells. In these cell and tissue studies, which involved herpes simplex virus (HSV) and varicella-zoster virus (VZV), HCF-1 was required to recruit LSD1 to the viral genome and initiate infection. HSV infection can cause cold sores and genital lesions, and VZV infection causes chickenpox and shingles.

When Dr. Kristie’s group reduced levels of either HCF-1 or LSD1, they noticed a corresponding decrease in the ability of HSV and VZV to express the viral genes necessary to continue infection. These results established the relationship between LSD1 and HCF-1 and the importance of each protein in initiating both HSV and VZV infections.

The scientists also knew from previous studies that LSD1 is similar to a family of enzymes whose activity is inhibited by monoamine oxidase inhibitors (MAOIs)—drugs used to treat clinical depression, anxiety and other disorders.

Therefore, the researchers tested the ability of the MAOI drugs pargyline and tranylcypromine (TCP) to inhibit HSV and VZV infection and observed significantly decreased levels of virus. The observation identified LSD1 as an essential control component and target for preventing herpesvirus infection.

After the initial infection, both HSV and VZV enter a latent state in nerve cells of the infected host.  Periodically these viruses can reactivate to produce infection and disease. The researchers demonstrated that, in addition to preventing infection, the MAOI drug TCP also prevented HSV reactivation. Importantly, says Dr. Kristie, the study contributes to the understanding of the mechanisms used by these viruses to infect host cells and of their cycles of latency-reactivation.

“As LSD1 is a well-defined target of MAOIs and these pharmaceuticals are widely used therapeutically, these observations identify a novel therapeutic target for herpesvirus infections and enhances the importance of ongoing efforts to develop additional LSD1 inhibitors,” the study states.

The researchers are continuing to analyze the unique HCF-1 protein complex to identify other components that are important for initiating herpesvirus infections and reactivating these viruses from latency.

Media inquiries can be directed to the NIAID Office of Communications at 301-402-1663, niaidnews@niaid.nih.gov.

Most of us can handle the ups-and-downs of our daily stress, even the occasional catastrophe. We suck it up, dig deep, and persevere. However, some individuals have an altered stress-coping system which prevents them from managing daily stress. 

Retrospective studies show that the stress of emotional, physical, or sexual abuse during childhood increases the future risk of developing certain symptoms or illnesses. These illnesses include many of the same symptoms associated with low thyroid and fibromyalgia, including fatigue, poor sleep, chronic pain, chronic viral infections, anxiety, and depression.

Apparently, for some children and adolescents, too many traumatic or stressful events decondition their normal homeostatic stress-coping abilities. Thus, stress and particularly traumatic stress, early in life, may alter the set point of the stress response system rendering these individuals prone to stressful events later in life.  This most likely occurs from over-stimulation and depletion of certain stress-coping hormones including serotonin, norepinephrine, cortisol, and DHEA.

Research shows that patients with fibromyalgia have genetic tendencies that cause them to be affected more drastically by the ups and downs of stress. Fibromyalgia patients are also more likely to report a history of emotional, physical, or sexual abuse during childhood and adulthood, compared to other patient subgroups.

Sadly, I find that many of my fibromyalgia and CFS patients have experienced physical, emotional, or sexual abuse as a child.

Stress is the main culprit in low thyroid function as well.