Stealth Viruses and Chronic Fatigue Syndrome

From http://www.ccid.org

Stealth Viruses

Explore 10:17-19,2001

John Martin, M.D. Ph.D.
Center for Complex Infectious Diseases

What are Stealth Viruses?

Viruses are submicroscopic infectious agents that replicate inside cells. Viral illnesses are normally controlled by the body's immune system acting primarily through white blood cells called lymphocytes. These cells recognize certain viral proteins that provide the antigens targeted by specific lymphocytes, leading to an anti-viral inflammatory response. Not all viral proteins, however, can function as antigens for effective anti-viral immunity. Indeed, for many viruses, only a very few proteins are involved in lymphocyte recognition of virally infected cells. Loss of these critical antigenic proteins can allow a virus to essentially go unrecognized by the cellular immune system. When such viruses have managed to retain the capacity to damage cells, they can potentially cause a persistent infection resulting in a prolonged illness. The viral nature of such an illness is usually overlooked because of the absence of overt inflammation.. Atypically-structured cell-damaging (cytopathic) viruses were initially identified in patients with the chronic fatigue syndrome and in patients with more severe neurological and neuropsychiatric illnesses. The term "stealth" was introduced to highlight their basic property of evading effective immune recognition, and also because they had gone unrecognized by the medical community.

Detection of Stealth Viruses

Stealth-adapted viruses can be most readily detected using specialized, semi-quantitative, viral culture methods developed and refined over the last decade. Using these procedures, stealth viruses will typically induce a characteristic vacuolating cytopathic effect (CPE) in cultures of human and animal-derived cells. Stealth virus infected cultures can be distinguished from cultures of conventional herpesviruses, adenoviruses, enteroviruses and retroviruses, by the appearance and host range of the CPE, and also by using selective immunological and molecular probe based assays, including polymerase chain reaction (PCR) testing methods.

Cytopathic Effects

A common feature of the CPE-induced, stealth adapted viruses is marked metabolic disruption. This is expressed as lipid accumulation, cytoplasmic vacuolization, formation of aberrant protein and lipoprotein inclusions, and abnormally shaped nuclei. Comparable foamy vacuolating cellular changes with atypical inclusion-like structures can be seen in detailed examination of brain and other tissues obtained from stealth virus infected patients and from animals inoculated with these viruses. Unlike infections caused by conventional cytopathic viruses, the actual production of readily identifiable viral particles is uncommon. Seemingly, the infected cells are metabolically impaired because various energy and other resources are diverted towards an inefficient and unbalanced synthesis of various virus coded components at the expense of normal cellular functions. Severe defects in energy-generating metabolic pathways are also apparent from the marked mitochondrial changes that are prominen
t in electron micrographs of virus-infected cells.

Center for Complex Infections Diseases

Both clinical- and research-based studies on stealth-adapted viruses have been undertaken at the Center for Complex Infectious Diseases in Rosemead, California. CCID is a non-profit organization under the National Heritage Foundation dedicated to understanding the nature, origin, disease associations, modes of transmission, methods of diagnosis and responses to therapy of stealth virus infections, and to the dissemination such information to the medical and lay communities. Information regarding CCID is available from the internet at www.ccid.org. Additional information is available from www.EmergingWorlds.com. The following sections provide a brief overview of some of the ongoing research activities being conducted at CCID.

DNA Sequencing Studies

A stealth virus isolated from a patient with a chronic fatigue syndrome like illness was originally noted to have limited DNA sequence homology to human cytomegalovirus (CMV). As additional sequence data became available, it became obvious that this virus was a derivative, not of human CMV, but rather of an African green monkey simian CMV (SCMV). Until the beginning of last year, these monkeys were routinely used to produce live poliovirus vaccine. Moreover, although not widely revealed, a joint Food and Drug Administration/Industry study in 1972 indicated that control kidney cell cultures from all 12 African green monkeys tested grew out SCMV, and that most of these isolates were not detectable using standard procedures.

Continued sequencing on the SCMV-derived stealth-adapted virus has shown interesting changes compared to a typical CMV. Of special note is the uneven representation of genes that encode various viral components. As expected, the genes that code the proteins known to provide major target antigens for anti-CMV cytotoxic T lymphocytes are either absent or mutated. Other genes are overly represented, including genes that code for various chemokines and for chemokine receptors. Interestingly, one of the markedly amplified chemokine receptor coding genes found in the stealth virus genome can also function as a receptor for HIV, suggesting a possible potentiating role of stealth viruses in HIV infected patients.

One set of amplified chemokine-coding genes detected in the stealth-adapted virus is of cellular, rather than viral, origin. Cellular genes can apparently be incorporated into stealth virus genomes, presumably during viral replication. The particular chemokine-coding cellular gene identified within the prototype SCMV-derived stealth virus was probably assimilated as a partially processed RNA molecule since it lacks the normal introns present in cellular DNA. This implies that stealth virus DNA replication is proceeding through RNA intermediates, and that it may, therefore, be dependent upon reverse transcriptase, as could be provided by an assimilated endogenous retroviruses. RNA to DNA replication is much more prone to error than is DNA to DNA replication. This might explain sequence variability between the three copies of the chemokine-coding cell-derived gene that have so far been identified within the stealth virus.

Chemokine receptor genes of both viral and cellular origins have been implicated in the development of several types of malignancies. It is somewhat worrisome, therefore, that the stealth adapted virus is apparently employing this type of gene for its survival. On the other hand, many therapeutic agents that appear to be of some benefit to stealth virus infected patients are known to inhibit cheomkine production and receptor activity.

Viteria

It has also been determined that stealth viruses have the ability to acquire genetic sequences of bacterial and even fungal origin. Normally, viruses that are infectious for human or animal cells (eukaryotic cells) will not infect bacteria (prokaryotic cells). Stealth viruses appear to have overcome this phylogenetic barrier. The term "viteria" has been coined to define eukaryotic viruses that have acquired bacteria-derived genetic sequences. The sources of the bacterial sequences include microorganisms that are not known to grow intracellularly within eukaryotic cells. This strongly suggests that stealth viruses become viteria by infecting bacteria.. Judging from the bacterial sequences so far identified, genes have been captured from a wide variety of both gram positive and gram negative bacteria. The linear arrangements of many of the bacterial-derived sequences are quite different from any of the known major bacteria, suggesting that an active ongoing selection process may be oc
curring to assist in stealth virus propagation within bacteria. Genetically empowered bacteria, carrying potentially oncogenic stealth-adapted viruses, could become a far more threatening biological weapons program then ever envisioned by military planners.

Bacterial sequences incorporated within stealth-adapted viruses may help explain positive findings in stealth virus infected patients in various tests for known bacteria, including Borrelia burgdoferi (the cause of authentic Lyme disease), mycoplasma (a suggested cause of CFS and Gulf war syndrome); chlamydia (implicated in coronary artery disease and Alzheimer's disease), etc. None of the commonly used assays for these bacteria actually detect cultured organisms, but instead rely upon broadly reactive molecular and/or serological testing that could as easily be explained by the presence of viteria.

Clinical Conditions Associated with Stealth Virus Infections

Stealth-adapted viruses have been recovered from the blood, cerebrospinal fluid, urine, throat swabs, breast milk, brain biopsies and tumor samples from patients with various neurological, psychiatric, auto-immune, allergic and neoplastic diseases. Examples of neurological illnesses are autism, attention deficit and behavioral disorders in children; depression, schizophrenia, amyotrophic lateral sclerosis, multiple sclerosis, chronic fatigue and fibromyalgia in adults; and neurodegenerative illnesses in the elderly. It is now known that the stealth viruses can infect many organs, but that the brain is especially prone to manifest the effects of even limited localized cellular damage. The varying manifestations of a stealth virus encephalopathy is probably heavily influenced by the timing of infection, regions of the brain that are mostly involved, genetic predisposition to particular symptoms and the additive pathology of any superimposed auto-immune component triggered by the viral induced cellular damage. CCID's focus is away from strict clinical categorization of stealth virus infected patients into discrete neurological and neuropsychiatric illnesses. This viewpoint has been supported by following individual patients over several years, and also by the not uncommon occurrences of related, yet diverse, illnesses occurring among other family members and even among household pets. Community-wide outbreaks of stealth virus infections have also been observed with individuals showing varying levels of severity and duration of illness. Neither the reporting of otherwise unexplainable deaths, nor the apparent "dumbing" of a whole township, as reflected in the excessive need for special education for its children, appears to provide adequate Public Health motivation to confirm CCID's findings of stealth-adapted viruses.

Cancer can now be added to the list of potential stealth virus-associated diseases. Positive stealth virus cultures have been seen in virtually all of the multiple myeloma patients tested, and in several patients presenting with other types of tumors. A previous history of a fatiguing illness and clinical indications of impairments in normal brain functions are suggestive of an underlying stealth adapted virus infection in a cancer patient. It will be interesting to determine the effect of stealth-virus suppressive therapy in such patients.

Infection Among Blood Donors

An indication of the probable prevalence of infection among apparently healthy individuals has come from studies conducted on student blood donors attending a college campus. Slightly less than 10% of the units tested gave a positive result. As a requirement of the study, it was not possible to determine the actual health status of these students. Nor were efforts allowed to follow recipients of the stealth virus positive blood units. Even if culture-positive individuals are presently asymptomatic, this would not preclude their being at risk for subsequent development of a stealth-virus associated illness. This concern is underscored by the apparent capacity of stealth-adapted viruses to "capture, amplify and mutate" various additional genes of viral, cellular and bacterial origins.

Role of Other Infectious Agents in Chronic Illnesses

Much of the debate over a potential infectious cause for many of the illnesses that are increasingly being seen within our society has centered upon conventional microorganisms. Patient support groups and their affiliating clinicians have championed alternative explanations for these illnesses. Human herpesvirus-6 (HHV-6), human herpesvirus-8 (HHV-8), enteroviruses and parvoviruses feature among the viral causes for these illnesses, while Borrelia burgdoferi, Mycoplasma incognitos and Ehlichiosis are being promoted as the bacterial causes for a wide spectrum of illnesses. As is the case for HHV-6 in CFS, HHV-8 in multiple myeloma, enterovirus in ALS and Borrelia in chronic Lyme disease, when looked at critically, the actual findings are generally inconsistent with a true etiological relationship. None of these negative studies exclude the role atypically structured microorganisms; indeed, if anything they strongly support their presence. As alluded to above, stealth-adapted viruses can easily be mistaken in diagnostic tests for conventional viral and bacterial pathogens.

Additional complex associations between stealth adapted viruses and conventional microorganisms may exist. For example, the lipid-laden cells infected with a stealth virus appear especially favorable to the growth of intracellular bacteria, including Borrelia, the causative agent of Lyme disease. CCID has demonstrated positive stealth virus cultures in blood samples from over 90% of patients referred with a diagnosis of chronic Lyme disease. Whether the patients are actually infected with Borrelia remains unproven, but if so, their growth may be dependent upon an accompanying stealth virus infection. Synergistic growth patterns between stealth adapted viruses and the viruses present in several live viral vaccine preparations, have also been observed. The potential role of stealth virus encoded chemokine receptors in the evolution and the present day expression of HIV, is also under consideration.

Clinical Approach to the Diagnosis and Therapy of Stealth Adapted Virus Infections (SAVI)

Diagnosis: A major challenge in providing medical care for stealth virus infected patients is the multiple and diverse clinical manifestations of the patients' illnesses. Individual patients do not fit comfortably into a single medical discipline, whether it is psychiatry, neurology, rheumatology, endocrinology, hematology, or any other. Imprecise diagnostic labels, such as CFS, fibromyalgia, depression, attention deficit, etc., and even the better defined diagnostic labels, such as schizophrenia, autism, ALS, multiple sclerosis, Alzheimer's disease, etc., tend to obscure the complex multi-system nature of the patients' illnesses. Another difficulty is quantitating the severity of disease processes that can vary widely over time, and can be influenced by such non-specific factors as stress, environmental exposures to chemicals, placebo effects, etc.

Disordered brain function can be anticipated in many stealth virus infected patients. This can be documented using a detailed neurological examination, with a focus on what are sometimes referred to as "soft" neurological signs. Ancillary, although expensive, tests such as SPECT scans, quantitative EEG and formal neurocognitive evaluations, can help substantiate a diagnosis of stealth adapted virus infection with encephalopathy. Additional syndrome names can be applied depending on clinical and laboratory findings. Tabulation of symptoms using a detailed questionnaire can be helpful in identifying clinical problems and in assessing therapy related improvements.

Therapy: Until the existence of stealth viruses is accepted by Public Health authorities, there will be no approved standard of care in providing anti-viral treatments. Several suggestions can be made, however, from what is currently known about the prototype SCMV-derived stealth virus. Whether these suggestions are relevant to atypical viruses cultured from other patients remains to be tested. CCID is now reaching out to clinicians involved with the care of stealth virus infected patients for assistance with these clinical trials.

Basically, it seems appropriate to undertake efforts to suppress stealth virus activation and at the same time to support cellular metabolism, especially mitochondria function. The remarkable expansion of chemokine and chemokine-receptor related genes within the prototype SCMV-derived stealth-adapted virus support the potential use of agents that can down regulate chemokine pathways. Fortunately, many of the widely used herbal and generally non-toxic allopathic medicines are known to interfere with chemokine signaling. It is probably more than a coincidence that many of the compounds have also been reported to benefit at least a proportion of patients with CFS and related illnesses. Ideally, patients receiving these relatively simple therapies would be retested for stealth virus activity. If there were no apparent reduction in stealth virus activity, and if the patient remained symptomatic, one could more easily justify the use of potentially more toxic allopathic medicines, incl
uding known anti herpesviral agents.

For patients with major neurological, psychiatric, autoimmune or malignant diseases, the stealth virus associated treatments will simply be an aside to the accepted standard care of the patient's underlying illness. Once sufficient supportive data are collected, it may be possible to proceed directly with anti-stealth virus therapy as the primary treatment for these severe disorders.

Request for Assistance with Clinical Therapeutic Studies

In support of these studies, CCID has begun to work with medical specialists treating major medical neurological, psychiatric, rheumatological and neoplastic illnesses, and also with orthomolecular clinicians experienced in the uses of alternative medicines. Stealth virus culture activity will be serially determined and correlated with the use of various therapeutic modalities and changes in clinical status. CCID can provide copies of patient questionnaires and an appropriate informed consent form. A database for integrating laboratory, clinical and pharmaceutical data, will be established and will be assessable to all participating clinicians. The type of program is urgently needed to address the major Public Health threat posed by stealth-adapted viruses and viteria.

Additional information and copies of various research publications on stealth viruses, requisition forms, etc, can be viewed at www.ccid.org. Clinicians wishing to participate in stealth virus research should contact CCID. Stealth virus testing requires an Acid Citrate Dextrose (ACD) yellow-topped tube of whole blood. While a $250.00 fee is required for an initial diagnostic assay, a subsequent test on the patient during or following therapy will be at no charge. Blood samples should be sent via Federal Express to CCID, accompanied by a physician request for testing. CCID is located at 3328 Stevens Avenue, Rosemead, CA 91770. Ph. (626) 572-7288, Fax (626) 572-9288, e-mail ccidlab@hotmail.com.