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TWiV 152 Letters

Atila writes:

Dear TWiVers,

I have heard recently that some types of herpes virus may protect us from bacterial infections. This made me remember of myxomavirus, viral oncotherapy and how tumor cells have a compromised immune response. Do you think it is possible that one of those long term herpes infections that cause no harm to the host could protect us from some kind of skin cancer?

Keep up the good work, and thanks Dr. Racaniello for the right pronunciation of my name at ASV

Atila

[herpesvirus latency confers protection against listeria: http://www.ncbi.nlm.nih.gov/pubmed/17507983]

David Knipe replies:

Skip Virgin had a Nature paper where they showed that murine herpes virus 68 could induce cross presentation against bacterial infections. There is an old literature on herpes viruses inducing Th1 helper and polyclonal B cell expansion (our paper was Nguyen, L.H., D.M. Knipe and R.W. Finberg. 1994. Mechanisms of virus-induced Ig subclass shifts. Journal of Immunology 152:478-484.). That is probably also a major component of the oncolytic virus effects, induction of innate responses and Th1 helper cell responses and inflammation. There could be some protective effect of latent and reactivating infections against other infections and cancer. So far, it has been too much of a long shot for any clinicians or epidemiologists to do any studies. I think that that is why we have not eliminated herpesviruses.

Bob writes:

Manchester United lost the services of Darren Fletcher with an unspecified "stomach virus" for 4 months.

As far as we know no Soccer Club sweeps their Training and Match Pitches for Faecal and other contamination ? These surfaces are regularly mown but it would seem reasonable that this would only break up contaminations and spread them wider ? Given that some of their players are earning £250,000 a week and may cost up to £50 Million to transfer in would you agree that screening was a worthwhile exercise and if so how often should it be done ?

Date: Tue 27 Sep 2011

Source: CIDRAP News [edited]

<http://www.cidrap.umn.edu/cidrap/content/fs/food-disease/news/sep2711newsscan.html>

Zoonotic rotavirus transmission may have occurred in Denmark

------------------------------------------------------------

In Denmark, 2 adults were infected in 2006 with a rare rotavirus strain closely related to animal strains, suggesting zoonotic transmission, according to a report today in Epidemiology and Infection. The strain, G8P[14], was found in 2 patients who lived in the same area, and nucleotide sequences of the VP7, VP4, VP6, and NSP4 genes of isolates from the 2 people were identical. In addition, phylogenetic analyses showed both viruses closely clustered with rotaviruses of cow and goat origin. The authors conclude, "The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8P[14] strains were acquired through direct zoonotic transmission events," which are uncommon.

Jane writes:

XMRV has come to mean the V62 clone that was created in Silverman's lab, as expressed by 22rv1 cell line, which has never been in the WPI labs.

Lombardi et al found gag and env sequences 99% similar to the prostate tumor-associated strains of XMRV (VP62, VP35 and VP42) yet Silverman's retraction was only for VP62, which incidentally is the clone used as a positive sample in just about all papers that failed to find any wild HGRV's at all. I wonder if all the conflicting results have something to do with the semantics surrounding the way the labels are applied?

When you bring in the years of research on what MLV's do in animal models, when you bring in the several earlier discoveries of retroviruses in patients with ME [called CFS since 1988], when you know people who have at the least improved their illness experience using anti-retrovirals (early days yet), you might not be so quick to dismiss the hypothesis.

To get to the BWG 3 results, the following criticisms of the methodology has been made by scientists, patients and advocates:

*The samples used were from patients who were continuing with their medication regimes, to include Ampligen and anti-virals.

*No preservative was used to preserve PBMC's in samples

*Negative controls were not proven to be negative

*Spiked positives were spiked with VP62

*Sample size was too small to draw meaningful results.

I'd love to hear what Vince thinks about these points

Conrad writes:

Dear Dr Racaniello,

As a person with ME/CFS, I want to thank you for volunteering to work on the Science Advisory Board. I was touched, though not surprised, by your comments on this week’s TWIV about meeting ME/CFS patients. You had kind of a baptism of fire in your encounters with ME/CFS patients reacting to your TWIVs about XMRV. Some people would have turned their backs on both the disease and the patients after that, or decided that we are all, indeed, just a bunch of crazies. The fact that you haven’t speaks to your humanity and empathy. Somehow you were able to understand how someone who is desperately ill could lose their objectivity, and you never seemed to assume that the ones who are angry and unkind speak for all of us. You also haven’t gloated or seemed happy to learn that XMRV wasn’t proved to be the cause. We need virologists of your caliber working to solve the puzzle of this disease, but even more, we need people with your compassion. So thank you.

[from virology.ws comments]

Thank you for your continued coverage of CFS and taking time to help the CFIDS association, I cannot thank you enough for this. As a patient with CFS I would love to see an episode dedicated to CFS as you mentioned. Logical scientific discussion with patients and treating physicians would really bring it home to people that this is real and serious.

The outlandish comments seen in news and blog articles have really overpowered a lot of rational dialogue on CFS and I worry it is doing a great deal of damage to the disease’s reputation. This has only amplified with the recent mess of XMRV. I am hoping an episode on CFS could help clarify to the people we need the most, the scientific community, that the rambling comments they see online are a gross misrepresentation of the patient population.

--

Thanks Dr. Racaniello for sticking with CFS and being part of the CFIDS Associations Science Advisory panel. The MECFS community has, I believe, benefitted greatly, from your objective inputs on XMRV and good luck with your work with the CAA.

Brian writes:

At the beginning of the podcast [episode 151] you say most of the CFS patients you talked to could remember the day their problems started with an infection.

There are many other syndromes that also begin with an infection. For one example, Guillain Barre Syndrome http://www.ninds.nih.gov/disorders/gbs/gbs.htm which can result in paralysis.

I think your answer is correct, that CFS or ME/CFS can be the result of an unusual immune reaction to any pathogen. It is much more likely to be an uncommon response to a common pathogen, than the typical response to an uncommon pathogen. It is also quite unlikely that there is a common precursor pathogen, like XMRV that then requires a "trigger" to set off the CFS.

I am a PhD virologist, not an MD or immunologist, but it is my understanding that Guillain-Barre Syndrome is detectable not only by the symptoms but also by being able to measure the human antibodies that attack myelin in each patient.

There are dozens of other illnesses/syndromes that are also caused by somewhat unusual or uncontrolled immune reactions to common things. Allergies are one. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is another. In many of these, there is no "line in the sand" between a severe case of CIDP and a mild case of Guillain-Barre for example. They are all related and sometimes perhaps even identical in every detail except the level of the reaction/problem.

It is very likely that some cases of CFS are undiagnosed or misdiagnosed Guillain-Barre or CIDP. Other cases may be lingering or permanent effects of a EBV infection.

Some percentage of the cases are sure to be not immune-based but depression or other causes. Just as there are hundreds of ways to end up with paralysis symptoms somewhat like Guillain-Barre Syndrome symptoms. Many other causes of chronic fatigue, such as heart and lung disfunction, get accurately diagnosed so the patients do not end up with an ME/CFS label on their problem(s).

It seems to me, that many of the problems with CFS have to do with lack of insurance coverage, fraudulent doctors/treatments, poor patient understanding of the "fuzzy lines" between one syndrome and another, etc...

The XMRV story was quite a fiasco, and it is not over yet. I hope the Science journal, and USA medical science, can learn something from this.

Brian

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