Mitglied bei


  • Startseite

  • ME/CFS - was ist das?

  • Artikel des Monats

  • Kommentare des Monats 

  • Medienberichte

  • News

  • Broschüren zu Diagnose und Behandlung 

  • Häufig gestellte Fragen zu ME/CFS

  • Humor und Kreatives

  • Weiterführende Links

  • Impressum/Disclaimer

  • Spendenkonto


    Suche auf cfs-aktuell:


    Eine weitere Suchmöglichkeit besteht darin, z.B. bei das Suchwort einzugeben und dann nach einem Leerzeichen den Zusatz

    Sie erhalten dann alle Seiten auf, auf denen der gesuchte Begriff vorkommt.

    Artikel des Monats Juni 2011 Teil 8

    Neues zu XMRV von der 15. Internationalen Retrovirologie-Konferenz

    in Leuven und Gembloux, Belgien vom 5. -8. Juni 2011

    Abstracts von der 15th International Conference on Human Retroviruses: HTLV and Related Viruses

    Bitte beachten Sie: 2012 hat sich herausgestellt, dass dieses XMRV keine Humaninfektion, sondern eine im Labor entstandene Chimäre war. Näheres unter Artikel des Monats Dezember 2012 - 1 auf dieser Website!


    Diese Zusammenstellung der XMRV-bezogenen Abstracts wurde ebenfalls von Jamie Deckoff-Jones zur Verfügung gestellt.

    Weitere Abstracts zu XMRV von der Konferenz in Belgien, die stark darauf schließen lassen, dass es sich um mehr als eine Kontamination handelt, finden Sie hier.
    Ebenfalls wichtig zu beachten sind die derzeit laufenden Projekte der National Institutes of Health.

    In der gleichen Woche hat ein Symposium zu XMRV in Belgien stattgefunden, über das hier in Kürze berichtet werden wird. Frank Twisk wird eine Zusammenfassung schreiben. Hier gibt es erste Berichte und Diskussionen von Teilnehmern.

    XMRV-bezogene Abstracts von der 15. Retrovirologie-Konferenz Juni 2011

    1. XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?
    Francois Villinger1,2*, Jaydip Das Gupta3, Nattawat Onlamoon4, Ross Molinaro1,2, Suganthi Suppiah1,2, Prachi Sharma5, Kenneth Rogers5, Christina Gaughan3, Eric Klein3, Xiaoxing Qiu6, Gerald Schochetman6, John Hackett Jr6, Robert H Silverman3

    "In fact, a single atraumatic mucosal exposure with a high dose of XMRV virus into the urethra resulted in infection of 1 out of 4 macaques providing proof of concept that such transmission is possible. However, additional work is needed to fully investigate potential modes of XMRV infection."

    2. Development of XMRV producing B Cell lines from lymphomas from patients with Chronic Fatigue Syndrome
    Francis Ruscetti1*, Vincent C Lombardi2, Michael Snyderman3, Dan Bertolette4, Kathryn S Jones1, Judy A Mikovits1

    "Therefore XMRV infection may accelerate the development of B cell malignancies by either indirect chronic stimulation of the immune system and/or by direct infection of the B-cell lineage . Since viral load in peripheral blood is low, these data suggest that B cells in tissues such as spleen and lymph nodes could be an in vivo reservoir for XMRV."

    3. Prevalence of XMRV in blood donors, HTLV and HIV cohorts
    Xiaoxing Qiu1*, Priscilla Swanson1, Ning Tang2, Gregor W Leckie2, Sushil Devare1, Gerald Schochetman1, John Hackett Jr1

    "XMRV seroprevalence ranged from 0 - 0.6% in US blood donors, HIV-1 infected and HTLV uninfected subjects. Notably, 4.1% of Japanese HTLV-I infected individuals were p15E reactive. Inspection of sequence homology between HTLV and XMRV revealed a high level of conservation within the immunodominant region of HTLV gp21 suggesting increased seroreactivity is due to cross-reactive antibodies."

    4. Multi-laboratory evaluations of XMRV nucleic acid detection assays
    Graham Simmons1,2*, John M Coffin3,4, Indira K Hewlett5, Shyh-Ching Lo6, Judy A Mikovits7,8, William M Switzer9, Jeffrey M Linnen10, Francis Ruscetti11, Simone A Glynn12, Michael P Busch1,2

    "The Blood XMRV Scientific Research Working Group was formed to facilitate collaborative studies into the impact of XMRV in blood donors. Studies will evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility; assess performance on specimens represented in existing blood donor repositories, and determine the prevalence of XMRV in donors." Phase III results expected soon. Phase IV will test a blinded panel of 300 blood donor samples.

    5. Immune correlates of XMRV infection
    Vincent Lombardi1, Deborah Goetz2, Max Pfost1, Cassandra Puccinelli1, Judy Mikovits1*

    "XMRV infection results in dysregulation of the immune response, either directly by infection of specific leukocyte subsets or indirectly through cytokine modulation."

    6. The effects of XMRV gene expression on the mouse prostate
    Daniel Rauch, Sirosh Bokhari, John Harding, Lee Ratner*

    "Breeding PRO-XMRV mice with PRO-XPR1 mice will allow us to test whether XMRV integration or gene expression can cause more advanced prostate pathology in vivo. With these XMRV mouse models we seek to address the question that remains unanswered to date as to whether XMRV is capable of causing prostate dysplasia or cancer in vivo."

    7. XMRV: usage of receptors and potential co-receptors
    Mohan K H G Setty*, Krishnakumar Devadas, Ragupathy Viswanath, Veeraswamy Ravichandran, Shixing Tang, Owen Wood, Durga S Gaddam, Sherwin Lee, Indira K Hewlett

    "XMRV replication was observed in GHOST cells that express CD4, and each of the chemokine receptors ranging from CCR1- CCR8 and Bob suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors. Infection of Lung epithelial cell A549 lacking XPR1 expression clearly indicates usage of other receptors by XMRV for entry into susceptible cells."

    8. Cell line tropism and replication of XMRV
    Krishnakumar Devadas, Mohan K H G Setty, Ragupathy Viswanath, Durga S Gaddam, Owen Wood, Shixing Tang, Jiangqin Zhao, Xue Wang, Veeraswamy Ravichandran, Sherwin Lee, Indira K Hewlett*

    "Replication of XMRV could be observed in cervical and lung epithelial cells, T-cell lines Jurkat and H9, B-cell line HL60, U937 cells and in primary PBMC and monocyte-derived macrophages. The levels of XMRV transcripts were lower in primary monocytes compared to T-cell lines suggesting less efficient replication in these cells."

    9. Structure of the xenotropic murine leukaemia virus-related virus matrix protein
    Michal Doležal1,2, Iva Pichová1, Tomáš Ruml2, Richard Hrabal3, Michaela Rumlová1*

    "Although the protein sequence of the XMRV-MA is very similar to that of the murine leukaemia virus matrix protein (MLV-MA), it varies in several amino acid residues. We compared the structures of the XMRV-MA and MLV-MA and found that those changes are localized in a few domains, mostly on the surface of the protein."

    10. 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 virus.
    William M Switzer1*, Hongwei Jia1, HaoQiang Zheng1, Shaohua Tang1, Rebecca A Garcia2, Brent C Satterfield2

    "Our findings are consistent with previous negative reports and do not support an association of XMRV or MuLV in the majority of CFS cases across the US."

    11. Detection of MLV-like gag sequences in blood samples from a New York state CFS cohort
    Maureen R Hanson1 , Li L Lee1, Lin Lin1, David E Bell2, David Ruppert3 and David S Bell4

    "gag sequences could be amplified from genomic DNA from LNCaP cells of some subjects after 4 or 6 subcultures following incubation with certain subjects’ plasma, indicating the presence of infectious virus in blood. All gag sequences detected in this cohort were more similar to the MLV-like sequences reported by Lo et al. (2010) than to the XMRV sequences reported by Lombardi et al. (2009). Detection of gag sequences in whole blood genomic DNAs that were negative for mouse IAP and mitochondrial DNA provides strong evidence for infection of humans with MLV-like viruses."

    12. Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns
    Mattia CF Prosperi , William M Switzer, Walid Heneine and Marco Salemi

    "Given the evidence of inter-tropic recombination in MuLV, detection and classification of recombination in XMRV using different MuLV tropism prototypes should be interpreted with caution. Despite using a small dataset, a strong phylogenetic signal in the alignments and highly resolved phylogenies inferred both by full-length and sliding-window approaches, different recombination programs reported conflicting results. These results suggest that identification of parental strains of the potential recombinants is difficult and that recombination in the highly genetically related MuLV have been occurring for some time."

    13. In vitro assembly of xenotropic murine leukemia virus-related virus CA-NC protein
    Romana Hadravová, Jitka ¿tokrová, Michal Dole¿al, Iva Pichová, Tomá¿ Ruml and Michaela Rumlová

    "We found that purified XMRV full-length CANC, starting with the conserved proline residue at the N-terminus of CA, was not able to assemble into particles. However, a modification of the N-terminus of CANC (modCANC) enabled formation of spherical particles. Moreover, the negative staining of the in vitro assembled particles of XMRV modCANC revealed different organization of protein layers in comparison to CA-NC of M-PMV."

    14. Human infection or lab artifact: will the real XMRV please stand up?
    Robert H Silverman

    "Xenotropic murine leukemia virus-related virus (XMRV) was first identified in 2005 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe and Asia have either observed or failed to detect XMRV in patients [prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME), immunosuppressed with respiratory tract infections] or normal, healthy control individuals. Among the confounding factors are the potential for lab contamination with similar or identical viruses or viral sequences originating in mice. In some studies, relatively contamination-resistant methods (e.g. IHC, FISH, and antibody detection) suggest that either XMRV or a similar type of virus is present in some patients. Evidence for and against genuine infections of humans with this intriguing virus (and/or related viruses) will be discussed."

    15. XMRV infection in human diseases
    Otto Erlwein email, Mark J Robinson, Steve Kaye, Myra O McClure, Marjorie M Walker, Anup Patel, Wun-Jae Kim, Mongkol Uiprasertkul, Ganesh Gopalakrishnan, Takahiro Kimura and Kikkeri Naresh

    "The novel gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV) was identified in human prostate cancer tissue in 2006, confirmed in 2009 and later linked to a second human condition chronic fatigue syndrome, CFS. These investigations, all carried out in the US, have not been reproduced in Europe or in China.
    We found no evidence for XMRV infection in CFS. Moreover, we failed to find evidence of XMRV infection in UK prostate cancer patients and in prostate cancer tissue taken from patients in India, Korea, Thailand and Japan, or in cancers other than that of the prostate.
    Our UK CFS patients were consistently XMRV-free. We did, however, generate false-positive results from prostate cancer patient tissue, despite the fact that the no-template controls in our PCR were consistently negative and the PCR for murine mitochondrial DNA was often also negative.
    Sources of this contamination will be discussed in our presentation."


    Weitere Abstracts von der 15. Retrovirologie-Konferenz:

    Restricted infection of xenotropic murine leukemia virus-related virus in human lymphoid tissue
    Marta Curriu, Jorge Carrillo, Marta Massanella, Elisabet Garcia, Bonaventura Clotet, Julian Blanco, Cecilia Cabrera

    Heme oxygenase-1 activation inhibits XMRV pathogenesis and carcinogenesis in prostate cancer cells
    Subhash Dhawan

    A prototype RT-PCR assay for detection of XMRV in multiple human sample types
    Ning Tang, Andrea Frank, Robert Kowal, Gregor Leckie, John Hackett Jr, Graham Simmons, Michael Busch and Klara Abravaya


    Laufende Projekte der National Institutes of Health:

    Sandra Ruscetti
    In collaboration with the laboratories of Judy Mikovits and Frank Ruscetti, we were able to use antibodies developed against the envelope protein of SFFV to detect infectious xmrv in the blood cells and plasma of patients suffering from the neuroimmune disease chronic fatigue syndrome (CFS). We were further able to develop a seroconversion assay using cells expressing the SFFV envelope protein to detect antibodies against the virus in the plasma of CFS patients. We now plan to apply our knowledge of the pathogenesis of mouse retroviruses that cause cancer and neurological disease in rodents to study the molecular basis for similar diseases associated with xmrv. We are in the process of developing rodent models for determining the biological effects of xmrv in vivo, which if successful will provide a small animal model for preclinical testing of potential anti-xmrv drugs. In addition, we are testing both in vitro and in vivo the biological effects of the envelope protein of xmrv, which like its related SFFV counterpart may be responsible for the pathogenicity of xmrv.

    Ila Singh
    Narrative: xmrv is a new retrovirus that was recently identified from human prostate cancers. This study will attempt to understand the replication of this virus in vitro and its association with cancer. We will explore mechanisms of oncogenesis in cells, in tumors, as well as in animal models, and carry out epidemiological studies to estimate prevalence of viral infection in the general population.

    Maribeth Eiden
    Our lab is recognized for our research on a similar gammaretrovirus isolated from nonhuman primates, gibbon ape leukemia virus (GALV). GALV is the only gammaretrovirus other than xmrv found in primates. In collaboration with Frank Ruscetti at the NCI, Bill Switzer at the CDC and Suzan Winfield and Jessica Siegal-Willcot at the National Zoo, we are investigating the source animal for xmrv, and screening gibbon apes in US zoos for the presence of GALV and xmrv. We have obtained samples from the CDC and the Biological Research Steering Committee that provide us with materials permitting us to determine that many gibbon apes at various zoos have been infected with an xmrv-like virus. We have determined the cell tropism of xmrv using an engineered biologically active xmrv virus with a GFP reporter gene and are identifying cellular factors that restrict xmrv infection of receptor bearing cells. These factors that can restrict xmrv infection will be used as a means of developing xmrv antiviral drugs. In addition to being a horizontally transmitted infectious agent, xmrv is a threat to the human genome. We are in the process of isolating rat germ line cells and exposing these cells to engineered biologically active xmrv virus with a GFP reporter. Sperm obtained from these cells are being assessed. Positive results of sperm expressing GFP indicate that xmrv can be transmitted from infected individuals horizontally (i.e., to offspring as a mendelian trait) as well as vertically through the more traditionally route of viral infection. We used cysteine scanning mutagenesis (SCAM) methods to assess the topology of the GALV receptor and intend to identify extracellular domains of the xmrv receptor using similar methods. These studies will lead to the identification of the xmrv-binding domain. Finally the spread of most retroviruses is mediated not by direct virus infection but by cell-cell transmission from an infected cell to an uninfected cell. We have developed a model system to assess blocks to cell-cell virus transmission using spinning-disc confocal microscopy to visualized individual budding of fluorescently labeled virus particles into adjacent cells in three dimensional space over time.

    Frank Maldarelli
    We have established useful collaborations with Drs. W. Marston Linehan and Peter Pinto (Urologic Oncology Branch, CCR) to study samples from patients with prostate cancer, and with Drs. Frank Ruscetti and Kathryn Jones (Laboratory of Experimental Immunology, CCR) and Dr. Judy Mikovits (Whittemore Peterson Institute) to study patients with severe CFS. As immune deficiency may contribute to infection by xmrv, we have also established collaborations with NIAID to obtain samples from study individuals with immune deficiency, including HIV-infected patients and patients with both HIV infection and prostate cancer. In addition, we are collaborating with Dr. Vinay Pathak (HIV Drug Resistance Program, CCR) in a study of xmrv pathogenesis and prostate cancer as part of a Bench to Bedside Award to Dr. Pathak. Reports of xmrv infection in individuals with chronic fatigue and in otherwise healthy individuals raised concerns regarding new health risks. Within a year of these reports, we have optimized a series of detection and analytical assays with excellent performance characteristics. In the next year, we will apply these approaches to shed new light on the potential role of mouse-related viruses in human disease.

    Arthur Horowitz
    In a related and collaborative project, we have joined Dr, Frank Ruscetti in his studies of the link between prostate cancer and xmrv, a recently-identified retrovirus associated with prostate cancer. Together, we are testing the hypothesis that inflammatory cells serve as a viral reservoir or infection route. We are characterizing the susceptibility of prostate-infiltrating myeloid cells (macrophages and dendritic cells) to xmrv infection. A long-term goal is to identify murine models to study the link between xmrv pathogenesis and prostate carcinogenesis.

    Susan Swedo
    D. Vargas et al (Johns Hopkins) demonstrated that individuals with autism and a history of neurodevelopmental regression had evidence of chronic brain neuroinflammation, as exemplified by activation of microglia and astroglia and the abnormal production of inflammatory cytokine and growth factors assayed in both tissue samples and CSF. The authors remarked that chronic microglia activation appeared to be responsible for a sustained neuroinflammatory response that facilitated the production of a number of neurotoxic mediators. Alternatively, neuroglial activation could occur in response to a secondary neurotoxic factor(s) and thus represent the result, rather than the cause, of the injury. Neuroglial activation requires the nuclear translocation of the pro-inflammatory transcription factor NF-kappaB. A small pilot study of minocycline, an antibiotic with known effects on NF-kappaB was undertaken in an effort to determine if the drug might have an effect on autistic behaviors or change patterns of distribution for the CSF or serum cytokines or chemokines. At the doses used in the pilot investigation, no clinically meaningful improvements were seen in behavior nor in the pattern of distribution of the CSF or serum cytokines or chemokines. Thus, no further investigations are planned for minocycline, but the search for novel therapeutic agents continues through the phenotyping study, where longitudinal assessments provide the opportunity to identify biomarkers of neuroinflammation in serial CSF and serum samples and to correlate the results of the assays with clinical symptomatology.

    Christine Kozak
    We are also interested in determining the extent to which virus resistance is mediated by polymorphisms of the cell surface receptor. We seek to analyze the XPR1 receptor for the xenotropic/polytropic gammaretroviruses and for xmrv, a xenotropic virus-like virus isolated from humans with prostate cancer or chronic fatigue syndrome.


    Symposium zu XMRV in Belgien am 9. Juni 2011

    Vrije Universiteit Brussels
    Pharmacy & Medicine Faculty
    Laarbeeklaan 103 – 1090 Brussel

    Judy A. Mikovits
    PhD (W.P.I., University of Nevada, U.S.A.)
    XMRV and other gammaretroviruses (HGRVs) in neuro-immune diseases

    Maureen Hanson PhD (Cornell University, U.S.A.)
    Assays for MLV-like virus sequences in a New York CFS cohort

    Cecilia Cabrera PhD (Irsi Caixa Foundation, Badalona, Spain)
    Infection of Xenotropic Murine Leukemia Virus-related virus in human lymphoid tissue

    Kenny De Meirleir M.D., PhD (Vrije Universiteit Brussel)
    Prevalence of XMRV in CFS/ME and in healthy blood donors