Absence of Xenotropic Murine Leukemia Virus-Related Virus in Italian Patients Affected by Chronic Fatigue Syndrome, Fibromyalgia, or Rheumatoid Arthritis

Maggi, Fabrizio; Bazzichi, Laura; Sernissi, Francesca; Mazzetti, Paola; Lanini, Letizia; Scarpellini, P.; Consensi, Arianna; Giacomelli, Camillo; Macera, Lisa; Vatteroni, Ml; Bombardieri, Stefano; Pistello, Mauro

doi:10.1177/039463201202500224

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…Furthermore, CFS samples previously reported to contain XMRV DNA were reexamined and no XMRV was detected [7]. In summary, subsequent studies cast massive doubts on the association of XMRV with CFS or prostate cancer [14–18] but XMRV remains a replication competent virus with novel biological features.…”

Section: Introductionmentioning

confidence: 99%

Utilization of Replication-Competent XMRV Reporter-Viruses Reveals Severe Viral Restriction in Primary Human Cells

et al. 2013

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The gammaretrovirus termed xenotropic murine leukemia virus-related virus (XMRV) was described to be isolated from prostate cancer tissue biopsies and from blood of patients suffering from chronic fatigue syndrome. However, many studies failed to detect XMRV and to verify these disease associations. Data suggesting the contamination of specimens in particular by PCR-based methods and recent reports demonstrating XMRV generation via recombination of two murine leukemia virus precursors raised serious doubts about XMRV being a genuine human pathogen. To elucidate cell tropism of XMRV, we generated replication competent XMRV reporter viruses encoding a green fluorescent protein or a secretable luciferase as tools to analyze virus infection of human cell lines or primary human cells. Transfection of proviral DNAs into LNCaP prostate cancer cells resulted in readily detectably reporter gene expression and production of progeny virus. Inoculation of known XMRV susceptible target cells revealed that these virions were infectious and expressed the reporter gene, allowing for a fast and highly sensitive quantification of XMRV infection. Both reporter viruses were capable of establishing a spreading infection in LNCaP and Raji B cells and could be easily passaged. However, after inoculation of primary human blood cells such as CD4 T cells, macrophages or dendritic cells, infection rates were very low, and a spreading infection was never established. In line with these results we found that supernatants derived from these XMRV infected primary cell types did not contain infectious virus. Thus, although XMRV efficiently replicated in some human cell lines, all tested primary cells were largely refractory to XMRV infection and did not support viral spread. Our results provide further evidence that XMRV is not a human pathogen.

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Section: Introductionmentioning

confidence: 99%

Utilization of Replication-Competent XMRV Reporter-Viruses Reveals Severe Viral Restriction in Primary Human Cells

et al. 2013

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“…Although, great efforts had been directed to look for MLV related infection in CFS patients only a few [33,36-38] included fibromyalgia patients in the studied groups, and only one of them included a larger cohort of patients that our study [33]. …”

Section: Discussionmentioning

confidence: 99%

Lack of evidence for retroviral infections formerly related to chronic fatigue in Spanish Fibromyalgia patients

Oltra

García-Escudero

Mena-Duran

et al. 2013

Virol J

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BackgroundThe etiology of fibromyalgia and chronic fatigue syndrome (FM/CFS) is currently unknown. A recurrent viral infection is an attractive hypothesis repeatedly found in the literature since it would explain the persistent pain and tiredness these patients suffer from. The initial striking link of two distinct orphan retroviruses: the gamma retroviruses murine leukemia virus (MLV)-related virus and the delta retrovirus T-lymphotropic virus type 2 (HTLV-2) to chronic fatigue have not been confirmed to date.ResultsGenomic DNA (gDNA) from 75 fibromyalgia patients suffering from chronic fatigue and 79 age-matched local healthy controls were screened for the presence of MLV-related and HTLV-2 related proviral sequences. The XMRV env gene was amplified in 20% of samples tested (24% patients/15% healthy controls). Unexpectedly, no PCR amplifications from independent gDNA preparations of the same individuals were obtained. None of the positive samples showed presence of contaminating murine sequences previously reported by other investigators, neither contained additional regions of the virus making us conclude that the initial env amplification came from spurious air-driven amplicon contaminants. No specific HTLV-2 sequences were obtained at any time from any of the 154 quality-controlled gDNA preparations screened.ConclusionsPrevious associations between MLV-related or HTLV-2 retrovirus infection with chronic fatigue must be discarded. Thus, studies showing positive amplification of HTLV-2 sequences from chronic fatigue participants should be revised for possible undetected technical problems.To avoid false positives of viral infection, not only extreme precautions should be taken when nested-PCR reactions are prepared and exhaustive foreign DNA contamination controls performed, but also consistent amplification of diverse regions of the virus in independent preparations from the same individual must be demanded.The fact that our cohort of patients did not present evidence of any of the two types of retroviral infection formerly associated to chronic fatigue does not rule out the possibility that other viruses are involved in inciting or maintaining fibromyalgia and/or chronic fatigue conditions.

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“…The explanations for fibromyalgia have varied as polar opposites. Some researchers have invoked explanations such as central sensitization or viral syndrome [ 12 , 13 ], while others regard fibromyalgia as a psychocultural illness [ 14 ]. While there are controversies in rheumatoid arthritis, this extreme spectrum of polar views does not exist.…”

Section: Introductionmentioning

confidence: 99%

Pain Mystery Score Beliefs: A Comparison of Fibromyalgia and Rheumatoid Arthritis

Ferrari

2014

International Journal of Rheumatology

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Objectives. To compare the mysteriousness scores of the Pain Beliefs and Perceptions Inventory in fibromyalgia. Methods. Two cohorts of patients, one with fibromyalgia (FM) and one with rheumatoid arthritis (RA), completed the Mystery Scale component of the Pain Beliefs and Perceptions Inventory to determine whether subjects in the two diagnostic groups had significantly different scores on the Mystery Scale. Results. A total of 126 subjects (64 FM, 62 RA) completed all questionnaires. The FM group had a greater percentage of female subjects, more severe pain, more severe anxiety, more severe depression, and a higher perceived injustice score. When the RA and FM group scores for the Mystery Scale were adjusted for age, sex, pain severity, HADS scores, and perceived injustice scores, the FM group still had a higher Mystery Scale score. Discussion. Fibromyalgia is associated with a higher level of perception of mysteriousness in the Pain Beliefs and Perceptions Inventory than is seen with rheumatoid arthritis. This difference appears to be independent of levels of pain, depression, anxiety, and perceived injustice. This sense of mysteriousness may reflect a lack of understanding of pain in fibromyalgia as previously reported and may be an area to be addressed in therapy.

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Absence of Xenotropic Murine Leukemia Virus-Related Virus in Italian Patients Affected by Chronic Fatigue Syndrome, Fibromyalgia, or Rheumatoid Arthritis

Cited by 8 publications

References 19 publications

Utilization of Replication-Competent XMRV Reporter-Viruses Reveals Severe Viral Restriction in Primary Human Cells

Utilization of Replication-Competent XMRV Reporter-Viruses Reveals Severe Viral Restriction in Primary Human Cells

Lack of evidence for retroviral infections formerly related to chronic fatigue in Spanish Fibromyalgia patients

Pain Mystery Score Beliefs: A Comparison of Fibromyalgia and Rheumatoid Arthritis

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