Viruses – Page 11 – American ME and CFS Society

Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently, CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blind manner using molecular, serological, and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS patients. We did not find XMRV or related MLVs either as viral sequences or infectious viruses, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV-related viruses, including XMRV, and the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.

Source: Shin CH, Bateman L, Schlaberg R, Bunker AM, Leonard CJ, Hughen RW, Light AR, Light KC, Singh IR. Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome. J Virol. 2011 Jul;85(14):7195-202. doi: 10.1128/JVI.00693-11. Epub 2011 May 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126563/ (Full article)

Chronic fatigue syndrome, XMRV and blood safety

Abstract:

In the past few months, there has been public discussion relating to a new perspective on blood safety and specifically upon measures to prevent or discourage donation by individuals with a diagnosis of myalgic encephalopathy-chronic fatigue syndrome. This reflects an intriguing interplay between science, public health and public concern and illustrates some of the difficulties of making decisions in the face of uncertainty and inadequate information.

Source: Dodd RY. Chronic fatigue syndrome, XMRV and blood safety. Future Microbiol. 2011 Apr;6(4):385-9. doi: 10.2217/fmb.11.24. https://www.ncbi.nlm.nih.gov/pubmed/21526940

XMRV as a human pathogen?

Abstract:

Xenotropic murine leukemia virus-related virus (XMRV) has been proposed to be associated with prostate cancer and chronic fatigue syndrome (CFS). This proposition has been controversial because many investigators have failed to replicate the reported associations. Here, we explore whether XMRV is an authentic human pathogen in the light of recent findings that indicate otherwise.

Source: Wainberg MA, Jeang KT. XMRV as a human pathogen? Cell Host Microbe. 2011 Apr 21;9(4):260-2. doi: 10.1016/j.chom.2011.04.001. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551452/ (Full article)

Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xenotropic murine leukemia-related virus

Abstract:

Recent reports showed many patients with chronic fatigue syndrome (CFS) harbor a retrovirus, xenotropic murine leukemia-related virus (XMRV), in blood; other studies could not replicate this finding. A useful next step would be to examine cerebrospinal fluid, because in some patients CFS is thought to be a brain disorder. Finding a microbe in the central nervous system would have greater significance than in blood because of the integrity of the blood-brain barrier. We examined cerebrospinal fluid from 43 CFS patients using polymerase chain reaction techniques, but did not find XMRV or multiple other common viruses, suggesting that exploration of other causes or pathogenetic mechanisms is warranted.

Comment in:

Reply to Schutzer et al. [Ann Neurol. 2011]

Extraordinary claims require extraordinary evidence. [Ann Neurol. 2011]

Source: Schutzer SE, Rounds MA, Natelson BH, Ecker DJ, Eshoo MW. Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xenotropic murine leukemia-related virus. Ann Neurol. 2011 Apr;69(4):735-8. doi: 10.1002/ana.22389. Epub 2011 Apr 6. https://www.ncbi.nlm.nih.gov/pubmed/21472770

No association of xenotropic murine leukemia virus-related virus with prostate cancer or chronic fatigue syndrome in Japan

Abstract:

BACKGROUND: The involvement of xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer (PC) and chronic fatigue syndrome (CFS) is disputed as its reported prevalence ranges from 0% to 25% in PC cases and from 0% to more than 80% in CFS cases. To evaluate the risk of XMRV infection during blood transfusion in Japan, we screened three populations–healthy donors (n = 500), patients with PC (n = 67), and patients with CFS (n = 100)–for antibodies against XMRV proteins in freshly collected blood samples. We also examined blood samples of viral antibody-positive patients with PC and all (both antibody-positive and antibody-negative) patients with CFS for XMRV DNA.

RESULTS: Antibody screening by immunoblot analysis showed that a fraction of the cases (1.6-3.0%) possessed anti-Gag antibodies regardless of their gender or disease condition. Most of these antibodies were highly specific to XMRV Gag capsid protein, but none of the individuals in the three tested populations retained strong antibody responses to multiple XMRV proteins. In the viral antibody-positive PC patients, we occasionally detected XMRV genes in plasma and peripheral blood mononuclear cells but failed to isolate an infectious or full-length XMRV. Further, all CFS patients tested negative for XMRV DNA in peripheral blood mononuclear cells.

CONCLUSION: Our data show no solid evidence of XMRV infection in any of the three populations tested, implying that there is no association between the onset of PC or CFS and XMRV infection in Japan. However, the lack of adequate human specimens as a positive control in Ab screening and the limited sample size do not allow us to draw a firm conclusion.

Source: Furuta RA, Miyazawa T, Sugiyama T, Kuratsune H, Ikeda Y, Sato E, Misawa N, Nakatomi Y, Sakuma R, Yasui K, Yamaguti K, Hirayama F. No association of xenotropic murine leukemia virus-related virus with prostate cancer or chronic fatigue syndrome in Japan. Retrovirology. 2011 Mar 17;8:20. doi: 10.1186/1742-4690-8-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065418/ (Full article)

Investigation into the presence of and serological response to XMRV in CFS patients

Abstract:

The novel human gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), originally described in prostate cancer, has also been implicated in chronic fatigue syndrome (CFS). When later reports failed to confirm the link to CFS, they were often criticised for not using the conditions described in the original study. Here, we revisit our patient cohort to investigate the XMRV status in those patients by means of the original PCR protocol which linked the virus to CFS. In addition, sera from our CFS patients were assayed for the presence of xenotropic virus envelope protein, as well as a serological response to it. The results further strengthen our contention that there is no evidence for an association of XMRV with CFS, at least in the UK.

Source: Erlwein O, Robinson MJ, Kaye S, Wills G, Izui S, Wessely S, Weber J, Cleare A, Collier D, McClure MO. Investigation into the presence of and serological response to XMRV in CFS patients. PLoS One. 2011 Mar 9;6(3):e17592. doi: 10.1371/journal.pone.0017592. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052320/ (Full article)

Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses

Abstract:

In 2009, a newly discovered human retrovirus, xenotropic murine leukemia virus (MuLV)-related virus (XMRV), was reported by Lombardi et al. in 67% of persons from the US with chronic fatigue syndrome (CFS) by PCR detection of gag sequences. Although six subsequent studies have been negative for XMRV, CFS was defined more broadly using only the CDC or Oxford criteria and samples from the US were limited in geographic diversity, both potentially reducing the chances of identifying XMRV positive CFS cases. A seventh study recently found polytropic MuLV sequences, but not XMRV, in a high proportion of persons with CFS. Here we tested blood specimens from 45 CFS cases and 42 persons without CFS from over 20 states in the United States for both XMRV and MuLV. The CFS patients all had a minimum of 6 months of post-exertional malaise and a high degree of disability, the same key symptoms described in the Lombardi et al. study. Using highly sensitive and generic DNA and RNA PCR tests, and a new Western blot assay employing purified whole XMRV as antigen, we found no evidence of XMRV or MuLV in all 45 CFS cases and in the 42 persons without CFS. Our findings, together with previous negative reports, do not suggest an association of XMRV or MuLV in the majority of CFS cases.

Source: Satterfield BC, Garcia RA, Jia H, Tang S, Zheng H, Switzer WM. Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses. Retrovirology. 2011 Feb 22;8:12. doi: 10.1186/1742-4690-8-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050813/ (Full article)

No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro

Abstract:

BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV), a novel human retrovirus originally identified in prostate cancer tissues, has recently been associated with chronic fatigue syndrome (CFS), a disabling disease of unknown etiology affecting millions of people worldwide. However, several subsequent studies failed to detect the virus in patients suffering from these illnesses or in healthy subjects. Here we report the results of efforts to detect antibody responses and viral sequences in samples from a cohort of German CFS and relapsing remitting multiple sclerosis (MS) patients with fatigue symptoms.

METHODOLOGY: Blood samples were taken from a cohort of 39 patients fulfilling the Fukuda/CDC criteria (CFS), from 112 patients with an established MS diagnosis and from 40 healthy donors. Fatigue severity in MS patients was assessed using the Fatigue Severity Scale (FSS). Validated Gag- and Env-ELISA assays were used to screen sera for XMRV antibodies. PHA-activated PBMC were cultured for seven days in the presence of IL-2 and DNA isolated from these cultures as well as from co-cultures of PBMC and highly permissive LNCaP cells was analyzed by nested PCR for the presence of the XMRV gag gene. In addition, PBMC cultures were exposed to 22Rv1-derived XMRV to assess infectivity and virus production.

CONCLUSION: None of the screened sera from CFS and MS patients or healthy blood donors tested positive for XMRV specific antibodies and all PBMC (and PBMC plus LNCaP) cultures remained negative for XMRV sequences by nested PCR. These results argue against an association between XMRV infection and CFS and MS in Germany. However, we could confirm that PBMC cultures from healthy donors and from CFS patients can be experimentally infected by XMRV, resulting in the release of low levels of transmittable virus.

Source: Hohn O, Strohschein K, Brandt AU, Seeher S, Klein S, Kurth R, Paul F, Meisel C, Scheibenbogen C, Bannert N. No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro. PLoS One. 2010 Dec 22;5(12):e15632. doi: 10.1371/journal.pone.0015632. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008728/ (Full article)

An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue

Abstract:

BACKGROUND: Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious or immune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectious agents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were the unaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time.

RESULTS: No novel DNA or RNA viral signatures were confidently identified. Four affected twins and no unaffected twins evidenced viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had previously undetected hepatitis C viremia. An excess of GB virus C viremia in cases with chronic fatigue requires confirmation.

CONCLUSIONS: Current, impairing chronic fatigue was not robustly associated with viremia detectable in serum.

Source: Sullivan PF, Allander T, Lysholm F, Goh S, Persson B, Jacks A, Evengård B, Pedersen NL, Andersson B. An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue. BMC Microbiol. 2011 Jan 2;11:2. doi: 10.1186/1471-2180-11-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022642/ (Full article)

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome

Abstract:

In October 2009, we reported the first direct isolation of infectious xenotropic murine leukemia virus-related virus (XMRV). In that study, we used a combination of biological amplification and molecular enhancement techniques to detect XMRV in more than 75% of 101 patients with chronic fatigue syndrome (CFS). Since our report, controversy arose after the publication of several studies that failed to detect XMRV infection in their CFS patient populations. In this addenda, we further detail the multiple detection methods we used in order to observe XMRV infection in our CFS cohort. Our results indicate that PCR from DNA of unstimulated peripheral blood mononuclear cells is the least sensitive method for detection of XMRV in subjects’ blood. We advocate the use of more than one type of assay in order to determine the frequency of XMRV infection in patient cohorts in future studies of the relevance of XMRV to human disease.

Source: Mikovits JA, Lombardi VC, Pfost MA, Hagen KS, Ruscetti FW. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Virulence. 2010 Sep-Oct;1(5):386-90. doi: 10.4161/viru.1.5.12486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073172/ (Full article)