Hi Gerwyn, Is there a study which links XMRV and CREB? I'd like to show it to my doctor. Thanks kdp
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
