1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
AVIVA Semi-Finals: National ME/FM Action Network is competing for $100,000
The National ME/FM Action Network in Canada is competing for $100,000 for biomedical research of ME and FM in the Aviva Community Fund contest. With thanks to all who helped, they made it through the first round of voting into the Semi-Finals.
Discuss the article on the Forums.

Xmrv brain fog and a lot lot worse

Discussion in 'XMRV Research and Replication Studies' started by Gerwyn, May 7, 2010.

  1. Rosemary

    Rosemary Senior Member

    Messages:
    193
    Likes:
    0
    Hi Mithriel,

    CREB has also been studied due to its involvement in drug dependence/drug addiction

    A good example below...Morphine Dependence in CREB-Deficient Mice

    " CREB phosphorylation could be part of the molecular pathway by which opiates produce changes in gene expression that lead to addiction."
    http://www.ncbi.nlm.nih.gov/pubmed/1531356?dopt=Abstract&holding=npg...therefore not a good thing !

    Within the central nervous system, cAMP-responsive element binding protein (CREB) activity is involved in many neuronal processes including neuronal survival (Lonze et al, 2002; Mantamadiotis et al, 2002), long-term memory (Bourtchuladze et al, 2002; Josselyn et al, 2002), molecular changes induced by antidepressants (Nibuya et al, 1996; Thome et al, 2000, Nestler et al, 2002), and drug dependence (Maldonado et al, 1996; Carlezon et al, 1998; Berke and Hyman, 2000; Nestler, 2001).

    http://www.nature.com/npp/journal/v29/n6/full/1300416a.html
    Modulation of Anxiety-Like Behavior and Morphine Dependence in CREB-Deficient Mice
     
  2. Rosemary

    Rosemary Senior Member

    Messages:
    193
    Likes:
    0
  3. Gerwyn

    Gerwyn Guest

     
  4. citybug

    citybug Senior Member

    Messages:
    522
    Likes:
    36
    NY
    Oh, is it this one?

    An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumor
    B Dong, S Kim, S Hong, J Das Gupta, K Malathi, EA Klein, D Ganem, JL DeRisi, SA Chow, RH Silverman

    We recently reported identification of a previously undescribed gammaretrovirus genome, xenotropic murine leukemia virus-related virus (XMRV), in prostate cancer tissue from patients homozygous for a reduced activity variant of the antiviral enzyme RNase L. Here we constructed a full-length XMRV genome from prostate tissue RNA and showed that the molecular viral clone is replication-competent. XMRV replication in the prostate cancer cell line DU145 was sensitive to inhibition by IFN-beta. However, LNCaP prostate cancer cells, which are deficient in JAK1 and RNase L, were resistant to the effects of IFN-beta against XMRV. Furthermore, DU145 cells rendered deficient in RNase L with siRNA were partially resistant to IFN inhibition of XMRV. Expression in hamster cells of the xenotropic and polytropic retrovirus receptor 1 allowed these cells to be infected by XMRV. XMRV provirus integration sites were mapped in DNA isolated from human prostate tumor tissue to genes for two transcription factors (NFATc3 and CREB5) and to a gene encoding a suppressor of androgen receptor transactivation (APPBP2/PAT1/ARA67). Our studies demonstrate that XMRV is a virus that has infected humans and is susceptible to inhibition by IFN and its downstream effector, RNase L.
    and
    Integration of the cDNA copy of the viral RNA genome is essential for retroviruses to establish a productive infection (for reviews, see reference [12]). However, because of its nonspecific nature, retroviral DNA integration is inherently a mutagenic event. Many retroviruses, especially members of the gammaretrovirus genus, can induce tumors as a consequence of integrating their viral genome into the host cell chromosome and activating proto-oncogenes via promoter or enhancer insertion, a mechanism referred to as proviral insertional mutagenesis [13]. XMRV is a member of the gammaretrovirus family, and does not encode host-derived oncogenes [1]. Genome-wide analyses of XMRV integration sites in a human prostate cell line, DU145, and prostate cancer tissues showed that XMRV integration favors gene-dense regions and genomic features frequently associated with structurally open, transcriptional regulatory regions of a chromosome, such as transcription start sites, CpG islands, and DNase hypersensitive sites [14]. The XMRV integration sites in prostate cancer tissues are further associated with cancer breakpoints, common fragile sites, and microRNA genes. However, no common integration site or integration hotspot has been detected within or near known proto-oncogenes and tumor suppressor genes in both acutely infected cells and cancer tissues [14]. Due to the relatively few integration sites (a total of 14) analyzed thus far in prostate cancer tissues, the role of XMRV infection in causing prostate cancer by insertional mutagenesis is still unclear.

    Then
    Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus, 2010
    ...However, certain mutations of the viral genome or reaction conditions can lead to uncoordinated integration of the two viral ends and result in deletions, insertions, or other rearrangements of the host DNA [25], [26], [27], [28], [29]. Therefore, in addition to insertional mutagenesis, uncoordinated integration of the two viral ends during integrative recombination may constitute another mechanism that can cause genomic alterations and initiate deleterious events in the infected cell. In this study, we have cloned and determined host DNA sequences flanking XMRV proviruses. We found that integration of XMRV DNA proceeds with high fidelity, and consistently produces a 4-bp direct repeat at the virus-target DNA junctions. Analysis of the 4-bp direct repeats reveals a weak consensus integration sequence.

    High fidelity-rare mutation? weak consensus integration?? what does that mean, seems contradictory to layperson
     
  5. Gerwyn

    Gerwyn Guest

    Ok I will give it a try.If you imagine that DNA is along strand of base sequences cut in two with the virus about to insert into the middle.The two bases at the left and right hand sides are duplicated by the insertion of the virus(high fidelity)

    The virus appears to target similar but not identical base sequences to "cut" into.That is weak consensus.Sorry if it is a s clear as mud!
     
  6. citybug

    citybug Senior Member

    Messages:
    522
    Likes:
    36
    NY
    Does that mean when the virus is selecting one spot on one side and then a base 4 units away on the other side it will automatically probably mess up our dna?

    Quote Silverman Fidelity of Target Site....
    Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site.
     
  7. citybug

    citybug Senior Member

    Messages:
    522
    Likes:
    36
    NY
    Did I get the right sections for linking CREB to XMRV at least?
     
  8. natasa778

    natasa778 Senior Member

    Messages:
    1,494
    Likes:
    1,364
    London UK
  9. citybug

    citybug Senior Member

    Messages:
    522
    Likes:
    36
    NY
    Thanks. So the virus could do mess up the splicing... and also inserts in different places? (or doesn't make the 2 ends match?)
     
  10. Advocate

    Advocate Senior Member

    Messages:
    506
    Likes:
    14
    U.S.A.
    Hi LJS,
    I'm glad to see you posting. I've sent you a PM. In case you don't know how to access it, check the third horizontal menu bar from the top, and the words "Private Messages" are second from the left.

    Advocate
     

See more popular forum discussions.

Share This Page