Thursday, January 23, 2014

Arthritis Associated with Exposure to Mimivirus?

Microbe Mimicking Virus - Mimivirus
A recent manuscript published in the Journal of Virology (which unfortunately is behind a pay wall) suggests that exposure to collagen produced by mimiviruses can potentially cause arthritis.

The giant DNA viruses e.g. Acanthamoeba polyphaga mimivirus, express collagen-like proteins that are similar in many ways to human collagens. Mimivirus replication or infection of humans has not been shown, and mimiviruses typically replicate in amoebae, however this manuscript demonstrates that roughly 30% of health (non-rheumatoid arthritis patients) and 36% of rheumatoid arthritis patients display a serum IgG response against the mimivirus capsid protein suggesting an immune response. Furthermore, human antibodies exist that recognize mimivirus collagen, and were frequently found in persons with rheumatoid arthritis.

A mouse model was also used by the group to demonstrate the ability of mimivirus to elicit antibody responses to collagen. The group showed that viral collagen was encoded by open reading frame L71 which is present at the surface of mimivirus particles. Exposure to mimivirus collagens elicited the production of anti-collagen antibodies in DBA/1 mice. DBA/1 mice are a widely used mouse model for rheumatoid arthritis.

DBA/1 mouse - commonly used rheumatoid arthritis model

One of the flaws to this study is the exposure method. While I understand that this is probably the best/cheapest model available to the researchers, the mice were exposed to mimivirus collagens by intradermal injection with mimivirus protein extracts. More than likely this would not be the "typical" route of exposure. I would also venture to guess that the dose used is significantly higher than what would be seen normally.

Overall, I am skeptical of the study. This is definitely an "extraordinary claims require extraordinary evidence" scenario. I don't think the authors have done enough to say "our study shows that environmental exposure to mimivirus represents a risk factor in triggering autoimmunity to collagens." I do think that it MIGHT pose a risk factor, but even with this Journal of Virology paper, it remains pretty doubtful in my mind.

The difference between "blood sera from healthy human subjects and from rheumatoid arthritis patients indeed demonstrated that 30% of healthy-subject and 36% of rheumatoid arthritis sera recognized the major mimivirus capsid protein" while statistically significant and powered, is not enough (especially considering Bayesian logic, and other corollaries discussed by Dr. John Ioannidis, which I will discuss in a later blog post).

The other data "six percent of healthy-subject sera recognized the mimivirus collagen protein (L71), and 22% of rheumatoid arthritis sera were positive for L71" is again, statistically significant, but not enough to walk this out as a risk factor. Potentially...maybe.

I would recommend going back and getting some more mechanistic data first before claiming exposure as a risk factor.

Lance D. Presser has a PhD in Microbiology and Immunology and currently is a Public Health Laboratorian.

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