XMRV symposium, June 9, 2011, Leuven, Belgium (part 2)
Do XMRV and HGRV (Human Gamma Retro Viruses) play a role in ME/CFS?
- diagnosis of exclusion
- > 6 months with no other explanation
- heterogenous
- including multiple immune and inflammatory abnormalities
- anti viral (RNase L) dysfunction
- low natural killer cells and functions
- they kill:
- tumor cells
- viral cells
- innate immune activation
- > number of activated T cells
- increased production of inflammation cytokines/chemokines
- chronic active infections - inflammatory syndromes
Definition: heterogenous [ˌhɛtəˈrɒdʒɪnəs]
adj
(Life Sciences & Allied Applications / Biology) Biology Med not originating within the body; of foreign origin
What do we know about XMRV?
The sequences originally identified in prostate cancer with the HPC1/RNase L gene are allelic variations, especially the R462Q single nucleotide polymorphism.
Integration in situ hybridization in unmanipulated human tissue and antibody responses demonstrate that
XMRV is a human infection although closely related to Xeno, Poly and MLV's.
XMRV is not an endogenous retrovirus in human.
How it got into humans is unclear.
Definition: endogenous /en·dog·e·nous/ (en-doj´ĕ-nus) produced within or caused by factors within the organism
It needs all of your cells to make more virions (virus particles) so it can multiply itself.
Virions have a complex structure and consist of an envelope, a nucleocapsid, and a nucleoid. Virions are spherical to pleomorphic measuring 90-100 nm in diameter[4] or 137 nm[3]. This is very small!
Dr Mikovits went through slides to explain the following studies:
The studies speak for themselves, you can find them here
1. Detection of an infectious retrovirus XMRV, in blood cells of patients of patients with chronic fatigue syndrome
2. Cell-free transmission of XMRV and MRV from PRC negative CFS patients plasma to LNCaP cells
In a study reported in 2009, DNA from peripheral blood mononuclear cells (PBMCs) of CFS patients and healthy controls from the US were tested for the presence of XMRV sequences. XMRV sequences were found in 68 out of 101 CFS patients (67%), as compared to 8 of 218 (3.7%) healthy US controls.
Viral gene sequences identified in CFS patients clustered with sequences from PC, and both sequences were virtually identical. Further investigation using activated CFS patient PBMC co-cultured with susceptible PC cells (LNCaP) showed that virus could be transmitted by cells and supernatant, as indicated by protein expression and transmission electron microscopy, suggesting that the virus being detected by protein expression was infectious.
Virus could also be transmitted in LNCaP cells from 10/12 CFS patient plasma samples. These studies suggested that both cell associated and cell-free transmission of XMRV is possible. Finally, antibodies to XMRV were detected in 9/18 CFS patients using a test based on the envelope of a closely related virus, spleen focus forming virus (SFFV).
Source: http://webcache.googleusercontent.com/search?q=cache:MBxg88Hnw9UJ:forums.phoenixrising.me/archive/index.php/t-8823.html+Cell-free+transmission+of+XMRV+and+MRV+from+PRC+negative+CFS+patients+plasma+to+LNCaP+cells&cd=4&hl=nl&ct=clnk&gl=be&source=www.google.be
3. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors
Study: http://thirdreviewer.com/2010/pnas-dump-file/detection-of-mlv-related-virus-gene-sequences-in-blood-of-patients-with-chronic-fatigue-syndrome-and-healthy-blood-donors/
Why do some groups fail to detect XMRV?
Variantions in XMRV sequences and low levels of replication of the virus in the blood are the main reasons why some groups fail to detect XMRV.
Clues to pathogenesis?
Hormones + Inflammation => Increase of replication of XMRV
XMRV is responsive to cortisol because stress is often onset to disease.
Stress can be a car accident, an operation, illness, ...
Question of the public: Is cortisol supplementation of hormone therapy detrimental?
Answer of Dr Mikovits: "Everything should be in balance and that includes cortisol."
A footprint of infection?
Can one recognize XMRV infection in the blood? Does it leave a footprint?
Dysregulated cytokine/chemokine production is detected in plasma from ME/CFS patients. It is a typical inflammatory signature of XMRV/MRV infection.
The Random Forest (RF) analysis reveals the inflammatory footprint
http://www.ncbi.nlm.nih.gov/pubmed/21576403
Full study here:
http://merutt.files.wordpress.com/2011/05/mikovits_lombardi-publikasjon-mai2001.pdf
Increased in ME/CFS and XMRV patients
CD3+
CD56+
NKT population
Of the CD19+ B cells, the % of CD20+, CD23+ are increased in XMRV patients.
Study: http://www.retrovirology.com/content/8/S1/A230
XMRV sequences in B cells from infected individuals have G to A changes.
Sequence data indicate there are different strains of XMRV/HGRV that can infect humans.
I guess she meant a change at the level of nucleotides:
Description of nucleotides at DNA level follows the recommendations of the IUPAC-IUBMB. Nucleotides are designated by the bases, in upper case, A (adenine), C (cytosine), G (guanine), T (thymidine), including those for uncertain nucleotides like Y (pYrimidine) and R (puRine).
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism.
More info at: http://en.wikipedia.org/wiki/Nucleotide
The last study she discussed was about an antiviral defense protein APOBEC3G that attacks viral RNA and changes is sequence.
Cell lines expressing APOBEC3G result in greatly reduced titer (x100) when infected with virus than cell lines that do not express A...
It has been well described in the study of Groom et al.,
http://www.pnas.org/content/early/2010/02/24/0913650107.full.pdf
