hhv6 mon uow "What is Human Herpesvirus 6 (HHV-6)? * HHV-6 one of the eight known members of the human herpesvirus family. * Note that HHV-6 is not the virus that causes cold sores, genital herpes, chicken pox, shingles, or infectious mononucleosis. Primary Infection HHV-6 was first discovered in 1986 in the United States at the National Cancer Institute. This virus infects human white blood cells, specifically T lymphocytes. Researchers have identified HHV-6 as the cause of childhood roseola (exanthem subitum). Symptoms of this illness include fever and a distinct type of rash. Most infants are infected with HHV-6 before age two, but many display mild or no symptoms. Some symptoms, such as fever, may be incorrectly attributed to conditions other than roseola. However, a small number of infected infants can develop serious disease including bone marrow infection (decreased production of white blood cells and platelets) and brain infection (seizures). Serologic testing reveals that more than 95% of the world's population is positive for antibodies to HHV-6, indicating an immune response to an infection by the virus. Transmission of this virus is believed to occur as a result of exposure to saliva. After this initial infection, HHV-6 viral DNA remains latent, or dormant, within the nuclei of cells. The Biologic Repertoire of HHV-6 The best data about HHV-6 disease comes from children with roseola. Symptoms noted in infants with roseola include fever, swollen glands, lethargy (fatigue), nervous system complications, and bone marrow suppression. HHV-6 is also known to infect and destroy the cells that produce myelin, the fatty coating that surrounds and protects nerve cells. Additionally, the virus demonstrates the ability to cause disruption of the normal functioning of the human immune system. HHV-6: Variants A and B Two variants of HHV-6 are recognized: HHV-6A and HHV-6B. Primary infection of HHV-6B is the cause of roseola in children and greater than 95% of the population has antibodies to this variant. Primary infection with HHV-6A is believed to occur later in childhood or during adulthood and may occur without symptoms. Latency and Reactivation HHV-6 reactivation in adulthood can result in illness. Reactivation means that the virus is no longer dormant and begins to replicate. In most individuals, reactivations are extinguished by the immune system and the virus is forced back into latency. Reactivations in Persons with Intact Immune Systems The factors that lead to reactivation in people with intact and functioning immune systems are unclear and probably include genetic and environmental causes (such as hormones, other infections, and exposure to chemicals). Most instances of reactivation will not result in chronic, active infection as the normal immune system will suppress the reactivated virus and return it to a latent state. However, reactivation of HHV-6 in normal adults has been associated with a mononucleosis syndrome, autoimmune disorders, and nervous system diseases. Recent studies have revealed active HHV-6 infections in single, random blood samples taken from Multiple Sclerosis (MS) patients (56% positive) and Chronic Fatigue Syndrome (CFS) patients (39% positive). Normal, healthy controls were negative for active HHV-6 virus (0% positive). This is a significant finding and demonstrates that active HHV-6 infections are not seen in healthy people without these disease associations. Reactivations in Persons with Compromised Immune Systems In individuals whose immune systems have been compromised by disease (e.g. AIDS) or treatment (e.g. chemotherapy for cancer or immunosuppressive drugs after transplantation), a reactivation of HHV-6 can result in suppression of the bone marrow or inflammation of the tissues of the brain, liver or lungs. Why is the Wisconsin Viral Research Group interested in HHV-6? * Work from several laboratories has strongly implicated HHV-6 as the cause of multiple sclerosis. * Other studies have suggested a role for HHV-6 in many cases of severe, persistent fatigue especially in patients with other signs of systemic disease (fever, swollen lymph nodes, cognitive impairment). * HHV-6 associated disease has been successfully treated with antiviral medications. * Recognition of the presence of active HHV-6 infections in MS, CFS, and other chronic diseases would allow for treatment of these patients" http://www.wisconsinlab.com/hhv6.htm 050307 ... mon uow "HHV-6 in AIDS The epidemic of the acquired immunodeficiency syndrome (AIDS) is in its second decade and continues its worldwide expansion. In some developing countries, more than 20% of all adults are infected with the human immunodeficiency virus (HIV).1 The successful use of multiple antiviral drug therapies has been limited by the complex dosing schedules required and by the emergence of resistant forms of HIV. Work on vaccines to prevent or treat HIV infections continues, but it appears that an effective vaccine is still several years away. Clearly, there exists a need for new strategies in the treatment of HIV disease, especially if these strategies can provide new targets for effective pharmaceutical or immunological therapies. Human herpesvirus six (HHV-6) may serve as an important cofactor in the pathogenesis of AIDS and may provide an alternative target for therapeutic intervention. Destruction of lymphoid tissues is the root cause of the severe immunodeficiency that characterizes AIDS. The reasons for this tissue destruction remain unclear. Because high levels of HIV are present in lymphoid tissues for years before damage begins, HIV is unlikely to be the direct cause.2 In addition, many of the dying cells in the lymphoid tissues of HIV infected patients are not infected with HIV.3 Thus, the event that first triggers the progressive destruction of HIV infected lymphoid tissues remains to be defined. Work by Wisconsin Viral Research Group (WVRG) has shown that HHV-6 reactivates to active infection early in the course of an HIV infection (absolute CD4 counts 500/mm3). Early on, these lymph node infections are predominantly due to the A variant of HHV-6 (HHV-6A). Furthermore, cell culture studies by WVRG have demonstrated infection with HHV-6A dramatically enhances the replication of HIV.4 Studies have explored the relationship between HHV-6A infection of HIV-infected individuals and the pathological changes present in the tissues. Lymph node biopsies from patients with progressive HIV disease were analyzed for evidence of active HHV-6A infection. All of the lymph node biopsies examined contained cells actively infected with HHV-6A. -Lymph node from an HIV-infected patient after staining for active HHV-6A. The infected cells are stained bright red. At the time of lymph node biopsy, the HIV-infected patient had a CD4+ lymphocyte count of over 300 per mm3 and did not have AIDS.- Interestingly, when the results from all of the biopsies were compiled, the densities of HHV-6A infections were significantly (p0.016) higher in lymph node areas undergoing active destruction than in areas free of destructive changes or in areas in which the lymphoid tissue had been replaced by scar tissue.5 Work by WVRG also has shown that, in tissues taken at autopsy, all the patients with AIDS had active HHV-6 infections in essentially every tissue. These observations strongly support Wisconsin Viral Research Groups’ hypothesis that active HHV-6A infection underlies the lymphoid tissue destruction that occurs in patients infected with HIV, probably through a synergistic interaction between HHV-6A infection and HIV. In this context, it should be noted that other investigators have presented data concerning the possibility of HHV-6 as a cofactor in the pathogenesis of AIDS. Numerous studies of the HHV-6 serological status of HIV infected individuals have resulted in contradictory conclusions. Such data is difficult to interpret because of the poor diagnostic and prognostic value of herpesvirus serology in immunocompromised patients. Corbellino et al.6 demonstrated that HHV-6 DNA is widely disseminated in the tissues of patients with AIDS at the time of their death, and Clark et al.7 found that patients with AIDS have significantly elevated levels of HHV-6 DNA in their tissues compared to normal control individuals. Similarly, Dolcetti et al.8 detected HHV-6 DNA in 65% of lymph nodes from HIV-infected patients, compared with 20% of lymph nodes from HIV seronegative individuals. HHV-6 positivity strongly correlated with AIDS specific pathological changes. In a longitudinal study of HIV-infected patients, Iuliano et al.9 demonstrated reactivation of HHV-6A infection in the patients and correlated this with a dramatic decline in the patients’ CD4+ lymphocyte counts. Emery et al.10 showed that the presence of HHV-6 in a tissue of an HIV-infected individual closely correlated with an elevated level of HIV in the tissue, consistent with previous observations by WVRG investigators. Finally, studies by Kositanont et al.11 have demonstrated an important role for HHV-6 in the development of AIDS in infants congenitally infected with HIV. The results from numerous laboratories have consistently indicated HHV-6, and especially HHV-6A, as an important cofactor with HIV in the development of AIDS." http://www.wisconsinlab.com/hiv.htm 050307 ... mon uow HHV-6 & Cancer "HHV-6 induced immune dysregulation puts patients with chronic active infections at risk for autoimmune disease and lymphoproliferative disease. Both beta herpesviruses (cytomegalovirus, HHV-6 and HHV-7) and gamma herpesviruses (Epstein Barr Virus and HHV-8) have been recently identified as risk factors for some types of cancer. EBV has been implicated in several types of lymphoma and HHV-8 has been implicated in Kaposi's sarcoma, although HHV-6 may play an important role as a cofactor. A recent study (Chun Lu, 2005) found that Kaposi's sarcoma would not develop without a co-infection of HHV-6. HHV-6 was discovered in patients with lymphoproliferative disorders and the virus has been linked to several including acute lymphoblastic leukemia, multiple myeloma and myeloproliferative disorder syndrome. HHV-6 has also been linked to oral cancer. HHV-6 involvement has been reported in Hodgkins Lymphoma, Non-Hodgkins lymphoma and Burkitt's Lymphoma, although further studies are required to demonstrate causation. It is difficult to study the disease associations in tissue by PCR given the high level of HHV-6 latent virus in the cells. HHV-6 may contribute to cancer indirectly through immune suppression. HHV-6 is one of the few viruses (other than HIV) that can directly infect CD4+T-cells. For reasons that aren't clear, HHV-6 can induce "apoptoses" (cell death) in CD-4+ cells even when the cells are not directly infected. HHV-6 can also infect natural killer cells, which are critical for protection against cancer and viral infection Kashanki (1997) found that HHV-6 genes have malignant transforming activity and the "ORF-1 oncogene" binds to p53, the tumor suppressor protein and inactivates it. This is not proof that an active HHV-6 infection is oncogenic (increases your chance of getting cancer) but it raises the level of suspicion." http://www.hhv-6foundation.org/hhv6cancer.html 050307 ... mon uow HHV-6 Overview "While it is generally known that this virus causes roseola and occasional seizures and encephalitis in infants, most physicians are not aware of other disease associations or the potential of HHV-6 to predispose patients to other disease states or influence the course of other diseases such as AIDS or MS causing them to progress more rapidly due to selective immunosuppression. HHV-6 viral infection results in increased levels ofinflammatory cytokines such as IL-1 and TNF α , and a steep reduction in IFNγ, which is necessary to fend off cancer, intracellular pathogens, viruses and mycobacteria. HHV-6, a beta herpesvirus in the same family as cytomegalovirus, was discovered in 1986 in AIDS patients with cancer and lymphoproliferative disorders. It infects close to 100% of children by the age of two, causing mild flu-like symptoms in some, but in some cases proceeds to serious rash, high fever, encephalitis and seizures. A surprisingly high percentage of pediatric emergency room visits are due to primary HHV-6 infections. In some areas as many as 13% of infants with acute HHV-6 infections develop seizures and other manifestations of encephalitis. The virus can persist in the CNS. In most cases, the virus goes into latency; however, in patients with impaired immune function, the virus persists in its active state at low levels for years. There are two distinct variants of HHV-6. Variant A or HHV-6A, is the predominant strain found in MS, CFS and AIDS patients. HHV-6B is the strain that causes roseola, febrile illnesses and encephalitis in infants, and reactivates in transplant patients leading to progression of CMV disease or rejection of the organ. HHV-6 suppresses bone marrow and can cause rejection or engraftment “no-take” in transplant patients." http://www.hhv-6foundation.org/overview.html 050307 ... mon uow "...Chronic Fatigue Syndrome Linked to HHV-6 Virus SANTA BARBARA, Calif., Feb. 18, 2005 (PRIMEZONE) -- The HHV-6 Foundation, an association formed to raise awareness, funding and further research for human herpesvirus 6 (HHV-6), has today announced that some cases of chronic fatigue syndrome (CFS) may be linked to human herpesvirus 6 A variant (HHV-6A). The announcement comes on the heels of the International Fatigue Conference on Fatigue Science that was held in Japan on February 9-11. The conference was attended by some 200 scientists from around the world. Studies examining the role of the virus in CFS have had conflicting results over the years. The HHV-6 virus was discovered in the late 80's. Although the B variant is very common -- over 95% of the population has had it -- and causes roseola in infants, the A variant is less common. The A variant has been linked to CFS and multiple sclerosis (MS) and may hasten the progression of HIV. Dr. Ablashi reported that when the correct testing method is used, there is a strong association between HHV-6 and CFS. Dr. Dharam Ablashi, co-discoverer of the virus and scientific director of the HHV-6 Foundation said, "There is good reason that it has taken a long time to build a case for this virus playing a role in chronic fatigue -- it's very difficult to find. The virus is 'neurotropic' meaning it prefers to live in the brain tissue. It is quite possible to find a significant infection in the brain tissue, but no virus in the serum by DNA testing." Dr. Daniel Peterson, a leading CFS clinician from Sierra Internal Medicine in Nevada, supported this finding. He performed spinal taps on patients with abnormal MRI or severe problems with cognitive functioning and found active HHV-6A virus in the spinal fluid of 20% of those patients. Twenty nine percent of these patients were positive at least once in the serum, and he found many patients who were positive in the spinal fluid but not the blood. Warned Peterson, "Just because you can't find it in the blood doesn't mean it isn't there." "Our primary objective at the moment is to get a test on the market that will be a sensitive indicator of active infection," said Kristin Loomis, executive director of HHV-6 Foundation. "The evidence presented at the conference will go a long way toward dispelling the notion, still held by some physicians, that CFS is purely psychiatric." There was a great deal of evidence presented at the conference in support of an infectious cause of CFS. Dr. Takeshi Sairenji of Tottori University showed evidence that 60% of CFS patients vs. 11% of controls had evidence of chronic activated antiviral pathways. He suggested that chronic fatigue might be caused by interferon from viral infections such as HHV-6, Epstein Barr virus and Borna virus. Dr. Peterson has been treating some of his most severe cases with intravenous antiviral therapy and the majority has responded. He does not tell them they have CFS; he tells them they have HHV-6A subacute encephalopathy. Others have begun calling it the Peterson Syndrome..." http://press.arrivenet.com/bus/article.php/592998.html 050307 ... nom) "Multiple Sclerosis Linked to HHV-6A Virus Evidence Presented at American Neurology Association Annual Meeting SAN DIEGO, Oct. 5, 2005 (PRIMEZONE) -- Dr. Claude Genain of the University of California San Francisco Medical Center presented evidence at the American Neurology Association Annual Meeting this week that shows a direct link between human herpes virus 6 variant A (HHV-6A) and a multiple sclerosis-like illness. Dr. Genain injected common marmoset monkeys with HHV-6 variants A & B. Most notably, only infection with HHV-6 variant A resulted in illness. The monkeys developed lab evidence and signs of chronic autoimmune demyelination of the central nervous system, the hallmark of multiple sclerosis. This is the first time that any animal infected with HHV-6A has developed clinical pathology of the central nervous system, and the most direct evidence to date of a possible causal connection between HHV-6A and multiple sclerosis. Dr. Genain's marmoset developed weight loss and paralysis with sensory deficits after exposure to HHV-6A. Inflammatory lesions of the central nervous system and evidence of demyelination were seen on MRI and microscope slides of the brain tissue. However, the important finding of the study was direct evidence of the presence of HHV-6 viral antigen within the nerve cells of the brain stained with an HHV-6-specific antibody. HHV-6 variant B (HHV-6B) causes roseola, a self-limited fever and rash, in over 95% of young children by age 2. After the initial illness, HHV-6 persists indefinitely in its quiescent, latent form in the cells of the central nervous system, bone marrow and immune system. However, HHV-6 can reemerge and actively replicate later in life, producing new virus particles that can cause illness. HHV-6 can reactivate in immunosuppressed patients and cause life threatening complications, such as opportunistic infections and encephalitis, in post-transplant patients. The quest for a theory of viruses as a causative agent for multiple sclerosis and other diseases has long eluded scientists. A direct link between infection with HHV-6A and multiple sclerosis has been lacking until now. According to Dr. Genain, "For the first time, scientists will be able to look into the biological process leading to multiple sclerosis at its very beginning, when no one suspects the disease and people have not yet experienced its symptoms." In recent years there has been a considerable degree of interest in the relationship between HHV-6A and multiple sclerosis, because HHV-6A DNA has repeatedly been found in brain tissue and the cerebrospinal fluid of affected patients, and increased levels of antibodies to viral antigens in their blood only present during replication of HHV-6A are frequently detected. A comprehensive analysis presented by Dr. Dharam Ablashi, co-discoverer of HHV-6 and Scientific Director of the HHV-6 Foundation, at the International Fatigue Conference on Fatigue Science held during February 2005 in Osaka, Japan, discussed all clinical studies published in the medical literature on the association between HHV-6A and multiple sclerosis. His summary of the existing literature demonstrates that when lab methods detecting the presence of active HHV-6A infection are used, an exceptionally strong, statistically significant association between HHV-6A and both multiple sclerosis and chronic fatigue syndrome (CFS) is consistently seen. Lab methods that detect latent HHV-6A virus are not able to consistently identify either MS or CFS patients. Having an experimental animal model linking HHV-6A infection to central nervous system pathology will open the door to new types of research investigations. The common marmoset has a well-known propensity to develop experimental autoimmune encephalitis, a chemically-induced animal model of multiple sclerosis that is commonly used when investigating the efficacy of new MS drugs. The inflammatory demyelination of nerve cells in a live primate model after exposure to the HHV-6A virus has now been demonstrated for the first time. This marmoset model will add a new dimension to the drug discovery and development process for multiple sclerosis. Dr. Ablashi, who has published numerous medical studies demonstrating the causative role of human and primate herpes viruses in various types of lymphomas and leukemia, commented, "Nonhuman primates are genetically closest to man. Dr. Genain's pathogenic model of HHV-6A infection in the common marmoset will enhance our understanding of the role that the HHV-6A virus plays in the induction of typical MS lesions. This model will be very important in the study of the disease process, and evaluation of new molecules that can prevent active HHV-6A viral infection and the development of multiple sclerosis."..." http://www.primezone.com/newsroom/news.html?d=87395 051102 what's it to you? who go blather from