Sunday, 17 November 2013

'MIKOVITS' DISEASE' - COMPETENT XMRV'S THROUGH RECOMBINATION!

Well this is an interesting piece of research - here

2013 Nov;87(21):11525-37. doi: 10.1128/JVI.01787-13. Epub 2013 Aug 21.

Generation of multiple replication-competent retroviruses through recombination between PreXMRV-1 and PreXMRV-2.

Delviks-Frankenberry K, Paprotka T, Cingöz O, Wildt S, Hu WS, Coffin JM, Pathak VK.

Source

Viral Mutation Section.

Abstract

We previously identified two novel endogenous murine leukemia virus proviruses, PreXMRV-1 and PreXMRV-2, and showed that they most likely recombined during xenograft passaging of a human prostate tumor in mice to generate xenotropic murine leukemia virus-related virus (XMRV). To determine the recombination potential of PreXMRV-1 and PreXMRV-2, we examined the generation of replication-competent retroviruses (RCRs) over time in a cell culture system. We observed that either virus alone was noninfectious and the RNA transcripts of the viruses were undetectable in the blood and spleen of nude mice that carry them. To determine their potential to generate RCRs through recombination, we transfected PreXMRV-1 and PreXMRV-2 into 293T cells and used the virus produced to infect fresh cells; the presence of reverse transcriptase activity at 10 days postinfection indicated the presence of RCRs. Population sequencing of proviral DNA indicated that all RCRs contained the gag and 5' half of pol from PreXMRV-2 and the long terminal repeat, 3' half of pol (including integrase), and env from PreXMRV-1. All crossovers were within sequences of at least 9 identical nucleotides, and crossovers within each of two selected recombination zones of 415 nucleotides (nt) in the 5' untranslated region and 982 nt in pol were required to generate RCRs. A recombinant with the same genotype as XMRV was not detected, and our analysis indicates that the probability of generating an identical RCR is vanishingly small. In addition, the studies indicate that the process of RCR formation is primarily driven by selection for viable cis and trans elements from the parental proviruses.

I have posted some time ago about XMRV here

1 comment:

Anonymous17 November 2013 at 18:58
Actually Coffin claims in this new paper that the replication competent retoviruses were in no way similar to XMRV. They were new. And XMRV was Silverman's lab contaminate that he sequenced. If a lab contaminate can produce replicating retoviruses just imagine what other mlv retoviruses used in xenografting in cancer research have a potential to do.
ReplyDelete
Replies

Add comment

Lyme Life written in 2009

I started suffering with arthritis in mainly my large joints especially my knees 6 years ago. The symptoms varied and I remember saying that every joint was affected except my elbows to one doctor. I was told it would be hormonal and to take the usual supplements cod liver oil or glucosamine ( I would certainly recommend buying shares in the companies producing these supplements) They had no noticeable affect.

All my symptoms deteriorated significantly over a few weeks,4 years ago. Hips shoulders and knees being the worst and I started with muscle weakness in upper arms and upper legs. I had difficulty standing and walking across a room. I was unable to walk upstairs and my husband was making plans to convert to a downstairs bedroom. I had seen 5 doctors and 3 Rheumatologists and put on steroids for Poly Myalgia Rheumatica diagnosis. I had been diagnosed with Fibromyalgia and ME/CFS.

I have X rays and scans showing signs of osteoarthritis and Rheumatoid arthritis. ( later note.- the X rays done some years into treatment showed my hands completely normal no signs of inflammation or RA confirming how they felt - normal) I have been retired early from the Civil Service having lost my job not to mention my earning potential. My illness seemed to progress through my body not affecting the same joints left to right at the same time. I had bursitis in left hip, right hip, left elbow. I had synovial thickening in both wrists. At that time I could not lift and hold a magazine so lifting a kettle I could only do if a third full and with two hands. Each joint in my hands fingers feet and toes were affected. I had swallowing difficulties and many other symptoms. None of this describes the endless and awful pain whenever I moved or the tiredness but inability to get quality sleep.

Two years ago my GP gave me Amoxicilin for a sinus/throat/chest infection. All my arthritis symptoms improved. The course ended the symptoms deteriorated I started a second course the symptoms improved. The improvement was more significant than when I had started taking steroids. This led my GP to suspect Lyme Disease. I laughed because we do not travel abroad but she said they had had other cases in the surgery in the early stages of tick bite and Erythma Migrans rash. She said but you have not had a bite. I said oh yes I have I had two on my ankles with rashes, March 05 this was confirmed on her computer when I had seen a locum doctor. My worst symptoms were waking up feeling rigid and having to painfully flex every joint in my body before struggling to get up. The only other time I had experienced this was in May 2003 during a flu like illness like no other I had ever experienced. At that time I had a bite and similar rash on my right foot which lasted like the other rashes about four weeks. I had also consulted the surgery and it was dismissed as a virus. I walked our dog daily in the woods adjacent to our house where the deer roam, prime tick area. Thus started my very lengthy search about Lyme Disease leading me through Lyme Disease Action to a doctor who specialises in this illness. He confirmed my GP's suspicions. I never had a positive blood test but then they are antigen tests and there is much research that shows they are unreliable. In my case the year of steroids and many weeks antibiotics could have affected the results. So with a clinical diagnosis and following ILADS International Lyme and Associated Disease Society guidelines I continued on antibiotics for two years. Both my doctors continued to treat me despite of Health Protection Agency advising against long term antibiotics. I am now nearly 100% recovered I have no pain or muscle weakness. I can walk upstairs something I could not do for three and a half years. I can garden do house work and live a normal life. I still need to pace myself and with only a few months to 60 will not be looking to return to work. Life is such a joy. Sadly there is much controversy about Lyme Disease and doctors in UK are taught that it is so rare. Well where I live in Guildford I have been in contact with a dozen other people with it so perhaps not so rare as HPA would like us to believe. I am in touch with nearly 2000 other patients through a chat line Eurolyme most had been misdiagnosed with several other illnesses. Look at UK charity Lyme Disease Action if you want to read more about this illness. There are many MP's taking an interest in the problems surrounding diagnosis and treatment see above charity links into a recent meeting at the House of Commons.

Thank goodness there are some thinking doctors around who have courageously treated me against opposition and I have made such a miraculous recovery albeit rather a lengthy one. One day there will be many more people who are helped with their chronic illnesses when IDSA starts taking note of what our courageous LLMD’s are doing following ILADS Guidelines.

ME/CFS, Fibromyalgia, Poly Myalgia Rheumatica, Arthritis, Bell’s Palsy, MS,MN, ALS, Parkinson’s, Alzheimer’s, Heart Block, Stroke, Psychiatric, gastric problems the list is endless. Not all suffering from Lyme Borrelia but how many are even properly assessed for it.

UPDATE

UPDATE 10 January 2012