HHV-6 versus HIV
Which is the real cause of AIDS? Will HHV-6 be declared the new HIV at the HHV-6 Conference in June, 2008? Would AIDS patients and CFS patients fare better medically if they were both considered to be manifestations of HHV-6 Disease? Is HHV-6 treatment the key to improving the lives of people with AIDS, CFS, autism, M.S., numerous forms cancer, neurological, coronary and many other medical problems?
"So, I believe human herpesvirus-6 is a factor in AIDS progression." --Robert Gallo http://history.nih.gov/NIHInOwnWords/docs/gallo3_01.html
"As far as immunologic damage? Oh, HHV-6A does it much more efficiently than HIV." --Konnie Knox Chronicillnet
"It seems wherever HHV-6 is going, you're bound to bump into HIV. It's like a cohabitation." --Robert Gallo http://www.aegis.com/news/newsday/1992/ND920206.html
". . . HHV-6 may participate in Kaposi's Sarcoma pathogenesis by promoting KSHV replication and increasing KSHV viral load. --Chun Lu et al., Human Herpesvirus 6 Activates Lytic Cycle Replication of Kaposi’s Sarcoma-Associated Herpesvirus, American Journal of Pathology. 2005;166:173-183
Although Dr. Anthony Fauci, the man in charge of AIDS research in the United States, attended the conference and presented the work his research group had performed on the lymph nodes of AIDS patients, neither he nor any other government scientist chose to comment about the parallel finding about T4 cells in the lymph nodes of AIDS and CFS patients. --Neenyah Ostrom http://www.chronicillnet.org/CFS/Ostrom/forward.html
"HHV-6 has been shown to infect endothelial cells and can establish chronic infection in these cells. . . . The infection of the cells can likely alter function of the endothelial cell and the cell surface, thus leading to activation of the coagulation pathways." --Dr. Joseph Brewer http://www.plazamedicine.com/hhv6/hhv6_1.html
"In an article in the Journal of Clinical Virology (in press), Dr. Dharam Ablashi, one of the world's leading experts on HHV6, concludes that CFS (ME/CFIDS) patients are acquiring HHV-6A as a primary infection as adults and not reactivating it from childhood as many have hypothesized." http://www.ncf-net.org/forum/ablashi.html
"Until the denial among medical professionals about the relationship between the AIDS and Chronic Fatigue Syndrome epidemics is overcome, however, it is difficult to imagine how either epidemic can be ended." --Neenyah Ostrom America's Biggest Cover-up http://www.chronicillnet.org/CFS/Ostrom/book_ToC.html
"Carrigan and Knox, meanwhile, were pursuing a theory that had been considered, and rejected, by researchers earlier - that HHV-6 might be a "co-factor" in AIDS, aiding and abetting HIV in the destruction of victims' immune functions. Soon, Regush relates, Knox was wondering, "was HIV doing any killing, or was HHV-6 the lone assassin?" But in 1997, after Carrigan and Knox found evidence suggesting HHV-6 might be killing alone, the British medical journal The Lancet rejected their paper for publication."
--Mark Nichols
Maclean's http://www.thecanadianencyclopedia.com/index.cfm?PgNm=TCE&Params=M1ARTM0012164
"ICL is 'non-HIV AIDS' or AIDS patients in whom HIV is not present. ICL is almost certainly 'HHV-6 AIDS.' The fact that non-HIV AIDS even exists and is acknowledged should be a major media event, a major medical discovery, and a cause for more research dollars. If the general public knew that non-HIV AIDS existed, much doubt would be cast on medical, governmental, and pharmaceutical company dollars spent on AIDS research. But money does play a role in healthcare that is frightening." --Dennis Gersten, M.D. http://www.lightconnectiononline.com/Archive/nov04_colums.htm
"But Dr. Cheney also has CFS patients with very low CD4 cells counts; so low, in fact, that they can be diagnosed as being "non-HIV AIDS," or ICL, cases." --Neenyah Ostrom, America's Biggest Cover-up
"I have either Chronic Fatigue Immune Dysfunction Syndrome (CFS/CFIDS) or a form of AIDS that is going undetected by HIV screening. Or, maybe I have both. I believe that I am living proof that the AIDS-like CFS is transmissible, something that the medical establishment seems unable to admit or to acknowledge. I also believe that I am living proof that Chronic Fatigue Syndrome and HIV-NEGATIVE AIDS are basically the same mysterious immune disorder." --a CFS patient (who wishes to remain anonymous)
"While most researchers have been concerned with HHV-6’s effects on the CNS, recent studies suggest HHV-6 may able to profoundly alter the functioning of the immune system. Rather startlingly it may be able to do so simply by binding to a protein found on the outer membranes of cells." --Cort Johnson http://www.phoenix-cfs.org/HHV-6.htm
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." http://www.immunesupport.com/library/showarticle.cfm/id/6291
"It doesn't take a rocket scientist to realize some very important implications here. Major targets of HHV-6 infection are T-cells, neuronal cells of the brain, central, and peripheral nervous systems, and the bone-marrow. Doctors listen up here! Any virus capable of directly infecting and thus altering the function of these types of cells cannot be good for you! Is it any wonder why many of us are so very ill and we are so dysfunctional. It is about time that doctor's take note and find out these critical facts for themselves by checking on the published literature via Medline since the CDC and the NIH certainly aren't going to tell the whole story yet!"
--Alan Cochetto
http://www.ncf-net.org/forum/infections.html
Thus, AIDS-associated cancers may represent examples of a process of immunosuppression allowing other oncogenic viruses such as EBV or the more recently discovered human herpes virus 6 (HHV-6) to be expressed as cancer (Cohen, 1991). --William A. Blattner, M.D. http://rex.nci.nih.gov/NCI_Pub_Interface/raterisk/risks107.html
Two new studies provide evidence that human herpes virus 6 (HHV-6) plays a role in AIDS-associated retinitis, and may even be a cofactor with HIV in the pathogenesis of AIDS. Anne -Marie Fillet and her colleagues in Paris suspected the presence of "an etiological link between HHV-6 and AIDS- associated retinitis" because of the "ubiquitous nature of HHV -6 and its genomic relationship with cytomegalovirus." They report in the Journal of Medical Virology that HHV-6 was found to be present in three cases of AIDS-associated retinitis, but not in a control group and concluded that "HHV-6 infects the retina but ... does not have an exclusive causative role in AIDS-associated retinitis. Meanwhile, another group of researchers, led by Donald R. Carrigan, report in the Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology that their research shows that "at the time of autopsy every patient with AIDS has an active infection with HHV-6 in essentially every tissue." The researchers conclude, therefore, that HHV-6A, a particular strain of the virus, is a necessary, but not sufficient, component in the pathogenesis of AIDS. Aegis.com http://www.aegis.com/news/ads/1996/AD961882.html
Why have we as a society been so quick to accept a theory for which so little solid evidence exists? Why do we take proclamations by government institutions like the NIH and the CDC, via newscasters and talk show hosts, entirely on faith? The average citizen has no idea how weak the connection really is between HIV and AIDS, and this is the manner in which scientifically insupportable phrases like "the AIDS virus" or "an AIDS test" have become part of the common vernacular despite no evidence for their accuracy. --Rebecca Culshaw "Why I Quit HIV" http://www.lewrockwell.com/orig7/culshaw1.html
She [Konnie Knox] won't divulge her views on AIDS science. For one thing, she and [Donald] Carrigan do keep an open mind on HIV. But their research on HHV-6 has taught them that that this virus often appears to be doing what HIV is supposed to be doing in different parts of the body such as the lymphoid tissue and brain tissue: it is killing cells. Their research also suggests that HIV may not always be necessary as a companion to HHV-6 when the herpes virus is destroying tissue. But even suggesting that in writing would raise the hackles of HIV researchers. In fact, some AIDS scientists compare any questioning of the HIV hypothesis, as it currently stands, to denial of the Holocaust. With such emotions running strong in AIDS science, why take a chance of boldly presenting alternative hypotheses? --Nicholas Regush, The Virus Within: A Coming Epidemic
Unfortunately early attempts to link HHV-6 and HIV in vivo were questionable due to the lack of reliable markers as a result of the poor quality of serologic testing available. Recently, the first conclusive in vivo evidence that HHV-6A acts as a promoting factor in the progression of primate immunodeficiency virus disease was observed in experimental coinfection studies in pigtailed macaques (Lusso et al., unpublished data). Coinfection with HHV-6A was shown to dramatically accelerate the immunological and clinical progression toward full blown AIDS in monkeys infected with a pathogenic simian immunodeficiency virus (SIV) strain and lead to death. Despite these results, further in vivo animal model and patient studies are needed to definitively establish the role of HHV6-A in AIDS. -- HHV-6 as a Progression Factor in AIDS, The HHV-6 Foundation
Human Herpes Virus 6 (HHV-6) is a β-herpes virus which was first isolated in 1986 from the peripheral blood of 6 patients with a variety of lymphoproliferative disorders, some of whom had AIDS. . . .It is estimated that HHV-6 is the single most common cause (10 – 40%) of children presenting to hospitals with a rash.
After the primary infection, the virus establishes a dormant latent infection in the individual for life. Re-activation of the virus can occur if the individual becomes immuno-compromised. Re-activation has been reported to be relatively common after solid organ and stem-cell transplantation.
These re-activations can cause skin rashes, hepatitis, bone marrow suppression, interstitial pneumonitis and encephalopathy. In some cases, the virus has been shown to cause allograft dysfunction.
HHV-6 is also thought to play a role in a number of diseases, including, the progression from HIV to AIDS, Multiple Sclerosis, Chronic Fatigue Syndrome and other neurologically-related disorders. Further study is required in these areas. --From Biotrin, a Biotech Company
By contrast, the patients who died of AIDS exhibited an almost generalized presence of HHV-6 throughout the organism. --Corbellino M, Galli M, Parravicini C, Balotta C, Moroni M, Gallo RC, Lusso P., Int Conf AIDS. 1992 Jul 19-24; 8: A28 (abstract no. PoA 2153)
What is probably the most likely cause of chronic fatigue syndrome is a virus that was first found in AIDS patients, a virus that was called human herpes virus 6. This is a very interesting virus because there are two types of the virus, one of which is found very widespread in the population, the other which is found in people who have cancer and chronic fatigue syndrome and AIDS and other immunological problems. That virus appears to be able to attack the immune system very, very successfully. I believe that it is going to be found to be instrumental in causing not only chronic fatigue syndrome but also AIDS and probably some forms of cancer. --Neenyah Ostrom, Radio Interview
Recent HHV-6 News
December 20, 2007
Herpesvirus May Play Role in Central Nervous System Diseases
Scientists have discovered evidence suggesting a herpesvirus may be responsible for some cases of meningitis and encephalitis. Researchers from the New York State Department of Public Health, Albany and SUNY, Albany report their findings in the December 2007 issue of the Journal of Clinical Microbiology.
Human herpesvirus 6 (HHV-6) is one of the most prevalent in humans. There are two variants of HHV-6, HHV-6A and HHV-6B which is attributed to a common childhood disease characterized by a high fever and rash. Studies indicate that by age 3 the majority of children have been infected by HHV-6, after which the virus persists in the salivary glands into adulthood. The virus may remain dormant or reactivate in immunocompetent or immunocompromised individuals.
Over a span of four years, researchers collected specimens from patients hospitalized with symptoms of encephalitis and meningitis, and tested them for the presence of HHV-6. The majority of the specimens were taken from cerebrospinal fluid and some of the symptoms exhibited by the patients include fever, altered mental status, and abnormal CSF profile, as well as seizures in those ages 3 and under. Results showed that 26 specimens from 24 patients were positive for HHV-6, of which 20 were identified as the HHV-6B strain. Forty-two percent of the patients were age 3 or under, possibly indicating primary infection, while the remaining patients ranging from 4 to 81 years old were probably experiencing viral reactivation.
“The detection of HHV-6 in specimens from patients diagnosed with encephalitis or meningitis, in the absence of a positive PCR result for other agents, strongly suggests a role for HHV-6 in the pathogenesis of these central system diseases,” say the researchers.
November 4, 2007
Source: Journal of Clinical Virology Vol. 37 Supplement #1, pp. S33-S38 Date: December 2006
Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue
Andreas M. Kogelnik(a), Kristin Loomis(b), Mette Hoegh-Petersen(c), Fernando Rosso(a,c), Courtney Hischier(b), Jose G. Montoya(a,c,*) a Stanford University School of Medicine, Stanford, CA, USA b HHV-6 Foundation, Santa Barbara, CA, USA c Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA * Corresponding author. E-mail address: gilberto@stanford.edu (J.G. Montoya).
Abstract
Background Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression.
Objectives We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir.
Study design Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study.
Results Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p=0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p=0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients.
Conclusion These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.
- Introduction
Chronic fatigue syndrome (CFS) is a clinically defined condition characterized by severe disabling fatigue and a constellation of symptoms that prominently feature self-reported impairment of concentration and short-term memory, sleep disturbances, and musculoskeletal pain. Patients suffering from CFS typically experience these symptoms for 6 months or longer. Suggested etiologies of CFS include, but are not limited to: viral or bacterial infections, endocrine-metabolic dysfunction, immunological imbalance, neurally mediated hypotension and depression (Afari and Buchwald, 2003; Fukuda et al., 1994). Most prior studies have found laboratory evidence that EBV and HHV-6 are reactivated more often in patients with CFS than in healthy control subjects or disease comparison groups, but causal inferences have not been made from such an association.
Epstein-Barr virus (EBV) and human herpesvirus type 6 (HHV-6) are enveloped double-stranded DNA viruses belonging to the herpesviridae family. Both viruses are lymphotropic and neurotropic, and both are capable of producing latent infections with immunomodulatory effects (Ambinder, 2003; Ambinder and Lin, 2005; Krueger and Ablashi, 2003). Furthermore, in vitro studies of co-infection with both viruses have revealed that a significant interplay may occur between them (Cuomo et al., 1998; Flamand et al., 1993). The clinical consequence of this interaction remains unknown. However, it has been suggested by various investigators that infection with EBV and/or HHV-6 may trigger or contribute to the pathogenesis of certain diseases including chronic fatigue syndrome (Bertram et al., 1991; Sairenji et al., 1995) and multiple sclerosis (Hollsberg et al., 2005).
The seroprevalence in the adult population for EBV and HHV-6B is about 90% and most people undergo asymptomatic seroconversion. The high seroprevalence in the general population complicates the interpretation of serological tests in diagnosing reactivation of either virus. Unlike many other viruses, the DNA for EBV and HHV-6 are difficult to detect in either the peripheral blood cells or serum except in cases of primary infection or acute reactivation. Most (Ablashi et al., 2000; Manian, 1994; Natelson et al., 1994; Patnaik et al., 1995) but not all (Buchwald et al., 1996) studies that have examined antibody titers to HHV-6 and EBV in CFS patients have found that there is a significant difference between patients and controls: Manian found 55% of CFS patients had EBV VCA antibodies of 1:320 or above compared to 15% of controls (Horwitz et al., 1985). Sairenji et al. found that CFS patients had elevated antibodies to EBV, HHV-6, human herpesvirus 7 (HHV-7) and ZEBRA (a protein of the immediate early EBV gene BZLF1) compared to healthy controls (Sairenji et al., 1995). Highly elevated early antigen (EA) antibodies are considered indicative of active infection for both EBV and HHV-6. Both Patnaik and Ablashi found elevated antibodies to the HHV-6 EA antibody in CFS patients compared to controls (Ablashi et al., 2000; Patnaik et al., 1995).
HHV-6 and EBV infections can cause immunosuppression and HHV-6 can impair immune response to fungal infections (Cermelli et al., 2006; Sauce et al., 2006; Smith et al., 2005). We suspected that their symptoms could be the result of an immune dysregulation triggered by EBV and HHV-6, especially when reactivated jointly. Alterations in the immune system such as aberrant cytokine profiles have been proposed as the central abnormality in patients with other viruses such as parvovirus B19 (Kerr et al., 2003). Latent EBV and HHV-6 virus can also alter cytokines and induce sickness behavior (Glaser et al., 2006; Yoshikawa et al., 2002).
Valganciclovir is the only known antiviral drug with efficacy against both EBV and HHV-6 that can be administered orally. It has the potential for toxicity, but our experience in using the drug to treat reactivation of viral infections in immunocompromised patients (Gao et al., 2003; Montoya et al., 2001; Montoya, 2004) with minimal adverse effects has made us comfortable with this treatment. If patients are supervised properly, the risk of significant side effects is greatly reduced and antiviral treatment is manageable. We hypothesized that a long course (i.e. 6 months) of valganciclovir could effectively decrease or stop ongoing viral replication of both HHV-6 and EBV and result in a sustained clinical improvement (decrease in antibodies or resolution of lymphadenopathy and fatigue).
- Materials and methods
2.1. Patients
Twelve patients, ages 21-57 (75% female) were referred to the Infectious Diseases Clinic at Stanford University Medical Center between February 2004 and August 2005 because of their history of chronic fatigue syndrome suspicious for infectious etiology. Patients had been seen by at least five other physicians (range 5-20). Other causes of fatigue had been appropriately excluded. The following laboratory tests were within normal limits in each of the patients who were tried on valganciclovir: complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alanine aminotransferase (ALT), total protein, albumin, globulin, alkaline phosphatase, calcium, phosphorus, glucose, BUN, creatinine, electrolytes, and urinalysis. All patients met the CDC case definition for CFS (Fukuda et al., 1994) and all had neurocognitive complaints that included four or more of the following symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit and symptoms consistent with depression. In addition, all had a history of a "flu-like" onset.
2.2. Drug regimen, toxicity monitoring, and fatigue evaluation Valganciclovir (VGCV) was prescribed as 900 mg twice per day for three weeks followed by 900 mg every day to complete a total of 6 months on the drug. Ganciclovir was approved in June 1989 by the United States Food and Drug Administration for the treatment and prophylaxis of diseases caused by cytomegalovirus (CMV). Ganciclovir has been used at Stanford Medical Center since 1987 for the treatment of several viral diseases observed in immunocompromised patients (Montoya, 2004). A second oral formulation (valganciclovir or L-valine esther of ganciclovir) was introduced in 1991 and achieves serum levels similar to those reached by the intravenous form.
CBC's were followed twice per week for three weeks, followed by once per week for three weeks, and once per month thereafter until VGCV was discontinued. None of the patients in our cohort was taking drugs with known adverse hematological or renal effects. While on VGCV, patients were instructed to report any new symptoms and on each medical visit they were explicitly asked whether they had experienced fever, chills, unusual bleeding or bruising, infection, unhealed sores or white plaques in mouth, headache, seizures or gastrointestinal symptoms. Pregnancy was not a consideration for any of our patients in the childbearing age; none of them was sexually active. At baseline, and again at each visit, patients were asked to report on their current activity level as a percentage of their pre-illness activity level.
2.3. Serological and molecular testing
In each of the 12 patients, the following serological tests were performed: EBV Viral Capsid Antigen (VCA) IgG and IgM antibodies, antibodies against EBV nuclear antigens (EBNA), antibodies against EBV early antigens (EA), HHV-6 IgG and IgM antibodies and CMV IgG and IgM antibodies (Focus Diagnostics, Inc., Cypress, CA, USA). HHV-6 and EBV testing was done by IFA and CMV tests were done by ELISA. The HHV-6 kits were purchased at Panbio (Columbia, MD) and the EBV kits are FDA approved kits sold by the Products division of Focus Diagnostics. At initial evaluation, each of the 12 patients had a polymerase chain reaction (PCR) test performed in serum for the following viruses: EBV, HHV-6, and CMV.
2.4. Statistical testing
To compare EBV and HHV-6 serologic titers before and after valganciclovir therapy among the 12 patients, paired non-parametric tests were performed (Sign test). To compare demographic and serologic variables between those who responded to valganciclovir and those who did not, the Mann Whitney test was used. Statistical analysis was performed using the Epi Info Version 3.3.2.
- Results
As shown in Table 1, of the 12 patients, 9 "responders" had a dramatic improvement in their fatigue and central nervous system symptoms (p=0.007) and 3 "non-responders" failed to report any progress. Central nervous system symptoms such as "brain fog" and other cognitive abnormalities were among the first symptoms to improve. Most improvement of clinical symptoms occurred between weeks 6 and 12. In the first several months, significant improvement was observed in physical activity at home. Subsequently, each of the responders was able to return to work or full time activities. The new level of "near-normal" activity has been sustained for greater than 9 months (up to 31 months) after discontinuation of the drug at week 24 in each of the nine patients.
The mean age of the responders was 35.4 years (range: 14-57) and that of the non-responders 43 years (range: 28-52). Of the 9 responders, 9 (100%) experienced the onset of their chronic fatigue syndrome as a "flu-like" illness and 4 (45%) developed lymphadenopathy. Whereas of the 3 non-responders, only 1 (33%) had a "flu-like" illness at the onset of the disease and 1 (33%) developed lymphadenopathy. The activity level of both responders and non-responders was severely compromised, compared to pre-illness activity level, at baseline (10% in responders, 15% in non-responders).
All of the nine responders experienced an initial worsening of their already severe symptoms. This worsening occurred between weeks 2 and 4, and wassevere enough to make several patients stay in bed for several weeks. In one patient where the WBC differential data was collected, this worsening period coincided with a 25% drop in WBC count and an 80% drop in monocytes. The three non-responders did not experience this worsening in their symptoms.
None of the 12 patients experienced any side effects to VGCV that required its discontinuation or experienced abnormalities in their laboratory tests including clinically significant hematological toxicities.
IgG antibody titers against HHV-6 and EBV antigens at baseline and after valganciclovir therapy for the responders and non-responders are shown in Table 2. In responders, the median HHV-6 antibody titer dropped from 1:1280 to 1:320 (p=0.271) and the median EBV VCA titer dropped from 1:2560 to 1:640 (p=0.008). Two of the 3 non-responders had no significant change in their titers against EBV antigens after VGCV therapy and values were not obtained for the third. Two of the non-responders did not have elevated antibody levels that meet our current threshold for treatment, but had other evidence of a viral syndrome.
Of the 12 patients in our cohort, only one patient had a positive IgM for HHV-6 (patient #8). The 12 patients were negative for EBV VCA IgM antibody. Neither EBV, HHV-6 nor CMV DNA was detected by PCR in the serum; assessment of viral DNA on whole blood was not performed. Seven of the patients had high HHV-6 antibody titers (patients #2-6, 8, 9), five had elevated antibody titers to EBV (#1, 2, 6-8), and three had elevated antibodies to both viruses (#2, 6, 8).
Reduction in IgG antibody titers, duration of fatigue and level of activity change in 9 patients whose clinical improvement was associated with the use of valganciclovir are shown in Table 1. In three of the nine responders the EBV EA antibody dropped by four-fold or more. EBNA antibodies dropped in six of the nine responders. Of the 9 responders, 4 (45%) were positive for CMV IgG and 1 was positive for CMV IgM. Of the 3 non-responders, 2 were CMV IgG positive. Only one patient was positive for CMV IgM antibodies (patient #8).
November 2, 2007
The simultaneous presence and expression of human hepatitis C virus (HCV), human herpesvirus-6 (HHV-6), and human immunodeficiency virus-1 (HIV-1) in a single human T-cell
S ZAKI Salahuddin, Katherine A Snyder, Andre Godwin, Renu Grewal, John G Prichard, Ann S Kelley and Dennis Revie
Abstract (provisional)
We have developed a system that isolates and replicates HCV in vitro. These isolates are called CIMM-HCV. This system has made it possible to analyze the biology, nature, and extent of HCV variability, among other things. Individuals that are infected with HIV-1 are often also infected with HCV and HHV-6. In addition to HCV, our lab has systems for replicating HIV-1 and HHV-6. We asked whether all these viruses could infect the same cells. We report here the successful infection of a T-cell (CEM) by CIMM-HCV, HHV-6, and HIV-1. PCR analyses demonstrated that the CEM cells were productively infected by HHV-6A. RT-PCR showed that the same cell culture was positive for HCV and HIV-1. Co-infection of a T-cell by all three viruses was confirmed by transmission electron microscopy (TEM). All these viruses are highly cytolytic; therefore, triply-infected cells were short lived. However, HIV-1 and HCV co-infected cells unexpectedly lasted for several weeks. Viral replication was unhindered and the phenomenon of 'dominance' was not observed in our experiments. In addition, CIMM-HCV was present in the perinuclear space, suggesting their possible synthesis in the nucleus. This report is based entirely on viruses produced in vitro in our laboratories. As part of the determinations of host ranges of these viruses, studies were designed to demonstrate the infection of a single cell by these viruses and to study the consequences of this phenomenon. All measurements were made on cultured cells and cell culture supernatants. Virology Journal 2007, 4:106
October 25, 2007
Human Herpesvirus 6 (HHV-6)-associated Pleurisy After Unrelated Cord Blood Transplantation in Children With Chemotherapy-resistant Malignant Lymphoma.
Clinical and Laboratory Observations Journal of Pediatric Hematology/Oncology. 29(10):709-712, October 2007. Suminoe, Aiko MD *; Matsuzaki, Akinobu MD * +; Koga, Yuhki MD *; Kusuhara, Koichi MD *; Hara, Toshiro MD *
Abstract: Two children, 5 and 10 years of age, received unrelated cord blood transplantation (CBT) for malignant lymphoma. Both of them suffered from pleurisy with and without interstitial pneumonitis after transplantation. By the quantitative real-time polymerase chain reaction, human herpesvirus 6 (HHV-6) variant B DNA was detected in pleural effusion. This is the first report of HHV-6-associated pleurisy after hematopoietic stem cell transplantation. HHV-6-associated pleurisy should be considered as a complication after hematopoietic stem cell transplantation even in the absence of pneumonitis. Quantitative polymerase chain reaction is a useful tool for rapid detection of viral DNA, which may facilitate precise diagnosis and appropriate treatment.
Journal of Pediatric Hematology/Oncology, 10/25/07
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