Stealth adaptation of an African green monkey simian cytomegalovirus

Abstract:

DNA extracted from cultures of a cytopathic virus isolated from a patient with chronic fatigue syndrome was cloned into pBluescript plasmid. The nucleotide sequences of the plasmid inserts were analyzed using the BlastN and BlastX programs of the National Center for Biotechnology Information.

In confirmation of earlier studies, many of the sequences show partial homology to various regions within the genome of human cytomegalovirus (HCMV). The matching regions were unevenly distributed throughout the HCMV genome. No matches were seen with either the UL55 or the UL83 genes, which provide the major antigenic targets for anti-HCMV cytotoxic T-cell-mediated immunity.

This finding is consistent with the notion that certain viruses can avoid immune elimination by deleting genes required for effective antigenic recognition by the cellular immune system. The term “stealth” has been applied to such viruses. Comparisons were also made between the sequences of the stealth virus and the limited sequence data available on cytomegaloviruses from rhesus monkeys and from African green monkeys. These comparisons unequivocally establish that the virus was derived from an African green monkey simian cytomegalovirus.

 

Source: Martin WJ. Stealth adaptation of an African green monkey simian cytomegalovirus. Exp Mol Pathol. 1999 Apr;66(1):3-7. http://www.ncbi.nlm.nih.gov/pubmed/10331958

 

Cellular sequences in stealth viruses

Abstract:

Cloned DNA obtained from the culture of an African green monkey simian cytomegalovirus-derived stealth virus contains multiple discrete regions of significant sequence homology (p values ranging from 4 x 10(-3) to 1 x 10(-20)) to portions of known human cellular genes. The stealth virus was cultured from a patient with chronic fatigue syndrome (CFS).

Earlier studies had revealed considerable sequence heterogeneity within DNA fragments isolated from virus-infected cells. A set of polymerase chain reaction (PCR) primers generated different PCR products when tested on stealth virus cultures from 4 patients with CFS. Several of the PCR products also contain regions of significant partial homology to distinct cellular sequences, including sequences repetitively expressed throughout the cellular genome.

Stealth viruses may play an important role in the origins and in the genetic diversity of both viral and cellular sequences.

 

Source: Martin WJ. Cellular sequences in stealth viruses. Pathobiology. 1998;66(2):53-8. http://www.ncbi.nlm.nih.gov/pubmed/9645627

 

Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Case report

Abstract:

A cytopathic stealth virus was cultured from the cerebrospinal fluid of a nurse with chronic fatigue syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the patient’s culture yielded positive results with primer sets based on sequences of a previously isolated African green monkey simian-cytomegalovirus-derived stealth virus. The same primer sets did not yield PCR products when tested directly on DNA extracted from the cultures. The findings lend support to the possibility of replicative RNA forms of certain stealth viruses and have important implications concerning the choice of therapy in this type of patient.

 

Source: Martin WJ. Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Case report. Pathobiology. 1997;65(1):57-60. http://www.ncbi.nlm.nih.gov/pubmed/9200191

 

Genetic instability and fragmentation of a stealth viral genome

Abstract:

Partial sequencing was performed on cloned DNA obtained from cultures of a stealth virus isolated from a patient with the chronic fatigue syndrome. The results extend earlier findings showing regions of homology to cytomegalovirus (CMV). Although the virus is much more closely related to simian CMV than to human CMV, many of the cloned viral segments could be aligned with the human CMV genome.

The aggregate size of the aligned segments exceeds 100 kilobase pairs (kbp). Undigested viral DNA has a mobility in agarose gel electrophoresis corresponding to approximately 20 kbp. The virus, therefore, apparently exists in multiple fragments. Considerable sequence variation exists between individual clones which overlap to similar regions of the human CMV genome.

The fragmented genome and sequence microheterogeneity suggest that both the processivity and the fidelity of replication of the viral genome are defective. An unstable viral genome may provide a potential mechanism of recovery from stealth viral illness.

 

Source: Martin WJ. Genetic instability and fragmentation of a stealth viral genome. Pathobiology. 1996;64(1):9-17. http://www.ncbi.nlm.nih.gov/pubmed/8856790

 

Severe stealth virus encephalopathy following chronic-fatigue-syndrome-like illness: clinical and histopathological features

Abstract:

The clinical histories and brain biopsy findings of 3 patients with severe stealth virus encephalopathy are reviewed. The patients initially developed symptoms consistent with a chronic fatigue syndrome. One patient has remained in a vegetative state for several years, while the other 2 patients have shown significant, although incomplete, recovery.

Histological and electron-microscopic studies revealed vacuolated cells with distorted nuclei and various cytoplasmic inclusions suggestive of incomplete viral expression. There was no significant inflammatory response. Viral cultures provided further evidence of stealth viral infections occurring in these patients.

 

Source: Martin WJ. Severe stealth virus encephalopathy following chronic-fatigue-syndrome-like illness: clinical and histopathological features. Pathobiology. 1996;64(1):1-8. http://www.ncbi.nlm.nih.gov/pubmed/8856789

 

African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome

Abstract:

BACKGROUND: A cytomegalovirus-like ‘stealth virus’ had previously been isolated from a patient with the chronic fatigue syndrome (CFS).

OBJECTIVE: To determine the original derivation of this virus.

STUDY DESIGN: DNA sequencing of cloned regions of the virus was performed and the sequences were compared using BLASTN and FASTA analyses against the entire GenBank database. Viral sequences were also used to design primers for the polymerase chain reaction (PCR).

RESULTS: DNA and amino acid sequence comparisons showed that the stealth virus was more closely related to the Colburn strain of simian cytomegalovirus (SCMV) than to CMV of either human or rhesus monkey origin or to any other sequenced herpesvirus. Similarity, but non-identity, between the stealth virus and SCMV, was confirmed using PCR.

CONCLUSION: The findings implicate the African green monkey as the probable source of the virus isolated from this CFS patient.

 

Source: Martin WJ, Ahmed KN, Zeng LC, Olsen JC, Seward JG, Seehrai JS. African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome. Clin Diagn Virol. 1995 Jul;4(1):93-103. http://www.ncbi.nlm.nih.gov/pubmed/15566831

 

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome

Abstract:

A simian cytomegalovirus-related stealth virus, isolated from a patient with the chronic fatigue syndrome, induced an acute neurological illness when inoculated into cats. Histological examination of brain tissue showed foci of cells with cytoplasmic vacuolization and an absence of any inflammatory reaction. Electron microscopy confirmed the presence of herpes-like viral particles and viral-like products in the brain of an inoculated animal. These findings support the role of stealth viruses in the pathogenesis of human neurological diseases and provide an animal model to evaluate potential antiviral therapy.

 

Source: Martin WJ, Glass RT. Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome. Pathobiology. 1995;63(3):115-8. http://www.ncbi.nlm.nih.gov/pubmed/8821627

 

Stealth viruses as neuropathogens

Abstract:

Neuropsychiatric diseases viewed as multifaceted expression of a dysfunctional brain in which atypical responses are evoked by various sensory inputs. Disease entities have traditionally been classified according to the predominant manifestation ( ) without regard to the overlapping features of many of the diseases (+/-). Thus, mild to moderate pain, mood, cognitive, and neurosomatic symptoms are frequently present in chronic fatigue syndrome (CFS) patients. Fibromyalgia syndrome (FMS) is listed as an example of a predominantly chronic pain syndrome. Affect (mood) disorders include depression (Depress.), anxiety, panic reactions, blunted affect, mania, etc. Schizophrenia (Schizo.) is listed as an example of a major cognitive psychosis. Autism as well as various forms of dementia would be included in this category. Irritable bowel syndrome (IBS) is an example of a neurosomatic disease.

 

Source: Martin WJ. Stealth viruses as neuropathogens. CAP Today. 1994 Oct;8(10):67-70. http://www.ncbi.nlm.nih.gov/pubmed/10150189

 

Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome

Abstract:

An atypical virus, cytopathic for human and animal fibroblasts, was repeatedly cultured from a patient with chronic fatigue syndrome. Viral particles, suggestive of cytomegalovirus (CMV) were seen by electron microscopy. Infected cells did not, however, stain with antisera specific for CMV, herpes, simplex virus, or human herpes-virus-6. Polymerase chain reaction (PCR) assays for these viruses were also negative.

Two distinct products of approximately 1.5 kilobase pairs were amplified from virally infected cells using the human T lymphotropic virus-II tax gene reactive primer, SK44, in low stringency PCR. Sequencing of one of the amplified products showed a region of highly significant partial homology with the UL34 gene of CMV.

The sequence of the other PCR product did not correspond with CMV or any other virus. DNA was extracted from the material pelleted by ultracentrifugation of filtered culture supernatants. It migrated in agarose gels as a single band of approximately 20 kpb. The banded DNA was digested with EcoRI and cloned. A 2.2 kbp plasmid containing the CMV-related sequence identified within the PCR product was recovered.

Sequencing of this plasmid extended the region of partial sequence homology with CMV to include a portion of the UL35 gene of CMV. Initial sequencing of additional plasmids has confirmed the partial relatedness to CMV. The data indicate a novel type of CMV-related “stealth” virus that is able to establish a clinically persistent human infection.

 

Source: Martin WJ, Zeng LC, Ahmed K, Roy M. Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome. Am J Pathol. 1994 Aug;145(2):440-51. http://www.ncbi.nlm.nih.gov/pubmed/8053501