I listened to the webinar today and thought I would post my personal notes (subjective and might include innacuracies, of course):
Karin's notes on the XMRV Webinar 7/15/10
1. Prof. Racaniello talked about the current status of XMRV research (bench)
XMRV was discovered in 2006 in prostate cancer tumors. The virus was not detected directly in the tumor, but rather it
was recovered from CULTURED cells transfected with proviral DNA.
Prof. Racaniello then gave a 101 on retroviruses, how they integrate in the cell DNA (provirus), and how they
replicate. He emphasized a very important distinction in the two modes by which retroviruses replicate:
- production of new virions budding from infected cells, which is the primary replication mode of HIV,
- or, direct transfer of the provirus from one cell to another during cell division, which is the promary replication
mode of HTLV-1. In this case, the pathogenic consequence depends where the proviral DNA inserts in the cell's DNA and
how it might turn genes ON and OFF. Production of virions is not necessarily involved.
Prof. Racaniello then talked about what kind of studies need to be done, for instance to determine if XMRV is the
cause of a disease or just a passenger. He stated that case-studies are needed that have the following features:
- multi-city, multi-continent,
- well-defined patient population,
- look into transmission modes,
- determine the seroprevalence in healthy individuals,
- determine what fraction of infected people develop disease,
- use multiple assays simultaneously to determine infection, to avoid false negative/false postives: virus/proviral
DNA/viral proteins/antibodies,
- determine which tissues and cells the virus replicates in,
- is there a specific type of cells infected that could explain disease, as it is the case for CD4+T in AIDS,
- is there a consistent integration site that would explain pathogenesis.
Prof. Racaniello then presented a table listing the studies examining XMRV that have been published so far, and listed
some possible reasons for inconsistence in the results:
- selection of patients,
- geographic differences,
- differences in viral sequences,
- no standardized sensitive methods, this being the main issue in his opinion.
There he mentioned a very important point, in my opinion: THE SCIENCE LOMBARDI PAPER DESCRIBED THAT PCR WAS USED TO
DETECT PROVIRAL DNA IN PBMC. This is the method that most other papers tried to reproduce. THE METHOD OF IN-VITRO
CULTURE OF PBMC TO AMPLIFY XMRV HAS NOT BEEN PUBLISHED YET. This might be reason why other labs have issues
reproducing the Lombardi results.
Prof. Racaniello then explained the differences between HTLV-1 and HIV, noting that both are very different.
HTLV-1:
- transmitted cell to cell, not through free virions like HIV,
- multiplies as the cell divides,
- is detected by looking at antibodies in serum with ELISA,
- virus isolation is not used for diagnosis because there are no free virions,
- no proven antivirals exist to treat it,
- it is unknown whether eliminating the virus would impact the progression of the disease.
HIV:
- millions of viral particles can be detected in a milliliter of blood,
- is treatable by limiting the virus production with antiviral therapies HAART.
Prof. Racaniello then stated that animal models of XMRV will be needed to understand the disease. He mentioned the
rhesus macaques study, that was not published but was presented at a conference earlier this year. The animals had low
viral load in their plasma.
Prof. Racaniello then presented the history of AIDS and HTLV as examples of the amount of time needed from discovery
to treatment:
AIDS was discovered in 1982 and HAART started being implemented in 1995.
HTLV-1 was discovered in 1970 as the cause of ATL, Human T Cell Lymphoma. In 1986, it was also associated to another
disease, myelopathy. Since then, blood has been screened for HTLV.
HTLV-2 was identified in 1985 but so far has not veen associated with any disease.
Both HTLV and HIV are thought to have originated from non-human primates. XMRV likely originated from mice.
(My own note: interesting that so many different human retroviruses appeared in the 70's, and originated from animals
commonly used in laboratories: monkeys and mice.)
Prof. Racaniello finished his persentation with Koch's Postulate: how can it be determined if a given bacteria causes
disease. And how do adapt this postulate to viruses.
Prof. Racaniello's blog can be found on:
www.virology.ws
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2. Dr. Bateman talked about the clinical aspects of CFS (bed-side)
She started by stating that when she accepted this webinar invitation several months ago, she was hoping she would be
discussing the latest research done in Utah by Dr. Singh (spelling?). However, publication has been delayed and since
it has not been published yet she cannot say anything. She emphasized though that she was SURE we were going to hear A
LOT from this publication very soon...
She then spent a good part of her talk talking about the good things coming from the XMRV controversy, then was
disconnected.
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3. Q/A with Prof. Racaniello (Dr. Bateman still disconnected)
- End of Karin's notes -