Viral Mysteries: Chikungunya Virus

Posted by ERV on October 6, 2010
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I think a lot of kids get the wrong impression about the medical field via TV. I mean like, I like ‘House’. It is an entertaining TV show. But being an MD is absolutely nothing like that. Its not really a mystery novel. Its more like ‘cataract surgery 5 times today… and 15 times this week… yaaay…’ and ‘pap smears and prescriptions for yeast infections and UTIs all day… yaaay…’

So when I had an opportunity as a ‘pre-med’ to do summer research, it blew mah mind!!!! Everything everyone was working on was like a little specialized mystery novel. It was both fun and frustrating, and I felt like I was using every neuron in my brain to solve my ‘mystery’ for the summer. And you didnt just have to be ‘smart’ (hell, you really didnt even have to be ‘smart’)– you had to be MacGyver/Sherlock Holmes/Professor Layton smart. Notice the importance of things other people think are insignificant, see patterns in everything, make what you have do what you need.

Its one of the main reasons I ditched med school for grad school.

I just learned about a friggen sweet mystery in virology: Chikungunya virus.

Theres nothing mysterious about the virus itself. (+)ssRNA. Enveloped. Likes macrophages. Transmitted by mosquitos. When a human gets infected they have the usual viral symptoms (headache, muscle aches, fatigue) plus a massive fever (104 F) and ‘incapacitating’ joint pain. Like, on that pain scale, 0-10, people report ~8. :-/

Good news is, this virus doesnt kill you. The younger you are, the faster you will get better (young ones get better in less than 2 weeks, elderly need months/years…).

Heres the mystery: Some people get better, but months later, get the joint pain again. And then they get better. And then joint pain. And then they get better. Over and over and over.

Whats up with that?

There are some obvious answers.

1– The virus is still there. The people with chronic CHIKV may appear ‘better’, but they really arent better.

Nope. If you look in these folks blood during acute infection, there can be 20,000,000,000 viruses/ml of blood. :-/ When you test them once they get ‘better’… there is no virus, there are no infected cells.

Furthermore, even though all patients make antibodies and cytotoxic T-cells that recognize CHIKV, your adaptive immune system isnt really necessary to clear the infection. You can totally knock out that branch of the immune system in mice, infect them, and they can still get better. Humans usually clean up the virus before your adaptive immune response can even mature in response to CHIKV. And we know the antibodies people make are ‘good’– if you take antibodies from a recently recovered patient and give them to mice, and then challenge the mice with virus, the mice dont get sick. So antibodies and CTLs should be cleaning up any potential virus that might still be lingering around.

2– The antibodies are the problem. CHIKV leads to the development of autoimmunity that targets something in the joints.

Nope. No one can find auto-antibodies in chronic patients.

Turns out neither one of these wrong answers are totally wrong!

Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response

Heres what happens– People get infected. They get a huge immune response to the virus. The virus goes away. Their immune system goes back to normal…

Except in people who have the chronic disease, the virus doesnt really go away, and their immune system doesnt really go back to normal. One of the tell-tale signs was that even though immune cell counts went back to normal after acute infection, a couple of chemical messengers, IL-12 and INF-a, stayed elevated. IL-12 is a sign of inflammation. IFN-a is a sign of viral infection.

So these researchers went straight to the point– they took biopsies of the joints of people who had this chronic joint pain (the biopsies were for other purposes– too invasive to do them ‘just to see’). Even though systemically there was no virus, and immune cells were normal, in the joints shit was still going down!

There was virus, there was a ton of inflammation, tons of infected cells.

Look at the whole patient: Everything looks fine.
Look at the joint: AAAAAAAHHHHHH!!!!!

Well, that solves that mystery! Hurray!!

… but it opens up a whole new mystery novel. How the hell is this infection staying localized at the joints??? Joints are not immune privileged. These people make neutralizing antibodies, why arent they helping? These people make CTLs that target infected cells, why arent they helping? Why isnt the entire body responding to this localized infection????

Further avenues of research. :-D

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Comments

  1. #1 Keely
    October 6, 2010

    That is AWESOME.

  2. #2 gillt
    October 6, 2010

    Acupuncture directly into the joint would clear this right up.

  3. #3 Chiefley
    October 6, 2010

    Man, this is fun and compelling science journalism, for just a few short paragraphs. Thanks for writing stuff like this.

  4. #4 Art
    October 7, 2010

    Just a wild-assed guess but I speculate that the virus hides in the cartilage. That cartilage in the major joints is perpetually being worn down and rebuilt. That the active virus gets encased in cartilage by this process and that the natural cycle of turnover of cartilage exposes fragments so the messengers are activated. Periodic major reworking of cartilage frees large amounts of the virus. Which triggers a major immune response and periodic bouts of arthritis.

    And for the minor cost of $100 million dollars and twenty years of intensive research and experimentation you will be able to prove me right. Or not.

    On the up side, by the time you know all the ins and outs of this oddity medical science will have a have gained a lot of detailed knowledge of arthritis, cartilage, and the balance between cartilage formation and removal that allows the joints to resurface themselves to compensate (or not) from wear, tear and abuse.

  5. #5 Charl
    October 7, 2010

    Deliver localised anti-virals directly to the joints and see if that helps? A bit like when my physio pumps Voltarol straight into my dodgy shoulder, rather than making me take it orally like my GP wants (which, coincidentally, is a lot cheaper and totally ineffective!)

  6. #6 Rorschach
    October 7, 2010

    That disease is bloody debilitating, seen a few patients with it.Interesting that the virus can later on be found in joints, and not systemically.I guess the joint hidey-holes have some vital part of the immune response missing that the virus uses to hang around.

  7. #7 titmouse
    October 7, 2010

    Hey after you sort the joint hidey-hole puzzle (insert subluxation joke here), take a look at the MovableType settings or whatever ScienceBlogs uses to filter spam and trolls. Please tell me why I’m able to post from this old puter (that takes ages to boot so never use), while the post I’ll be sending in one minute from my newer puter will be spam trapped.

    I tried clearing all my cookies; didn’t help.

  8. #8 titmouse
    October 7, 2010

    (Insert joke about corrupt scientists hiding de troof about lifestyle prevention aka “wellness,” using yoga, regular spine adjustments, Reiki, polarity work, quantum healing, and a personalized blend of nutritional supplements based upon reams of expensive, dodgy lab tests.)

    There. Can I post or am I a trap?

    From ERV– I have no idea why this was spammed! You didnt use any trigger words or too many links, wtf!

  9. #9 Ken
    October 7, 2010

    What? the holistic approach failed?? hahhaha

  10. #10 Poodle Stomper
    October 7, 2010

    AIDS deniers would claim that the persistence of the virus despite the presence of neutralizing antibodies must mean that the virus is a fraud…or exists but isn’t harmful…or both (somehow). I surprised none commented here since clearly this must be the work of evil Big Virology!!!11!one!!!

  11. #11 cynical1
    October 7, 2010

    Primary infection in macrophages followed by latent infection in cartilage chondrocytes? Similar to herpetic viruses establishing primary infection in one cell type and latency in another? Then periodic reactivation induced by who knows what……

    Can +ssRNA viruses establish a latent infection?

  12. #12 ERV
    October 7, 2010

    cynical1– Can +ssRNA viruses establish a latent infection?

    No. :) ssRNA is not stable ‘on its own’. It cant just hang out in the cell, chillin until it wants to be active. And it especially cant hang around during the dsRNA steps of its lifecycle (cells really hate dsRNA. they destroy that shit if they see it).

    Its another mystery :-D

  13. #13 gf1
    October 7, 2010

    Interesting stuff. I wasn’t able to find much about this, but it made me think (as everything does) of CFS.

    This paper seems to talk of the increased medical problems found in those with Chikungunya as probably being just another example post-viral syndrome, with their reference for this (29) being to a paper examining the validity of CFS as a diagnosis.

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007800

    How likely is it that some similar mechanism could occur with other viral infections (glandular fever being most commonly linked to CFS)? Or we’ve no idea? ie: Is this some new clever technique that was used that may not have been tried on other infections, or would this sort of thing already have been ruled out?

    What about Lyme disease? ERV mentioned that this was a virus which hangs out in people’s joints – could something similar cause chronic problems for those infected with Lyme. (I’m still not really sure if those who have had Lyme disease tend to suffer post-viral syndromes at all, the whole conversation having been contaminated by self-diagnosis). Thanks.

  14. #14 not a tit nor a mouse
    October 7, 2010

    Were I not trapped, I’d tell gf1 that Lyme is a bacterium not a virus.

    Changing my user name, email, url, does not get me beyond the filter.

    It should be possible to figure out the variable that trips the anti-titmouse filter somehow.

  15. #15 gf1
    October 7, 2010

    ‘I’d tell gf1 that Lyme is a bacterium not a virus.’

    I was a bit unsure of that. I thought of calling it a bug to avoid making a needless error, but it seems I chose to be bold and wrong.

  16. #16 W. Kevin Vicklund
    October 7, 2010

    IP blocking, perhaps? That used to happen to me on PT every once in a while (major DSL brand with dynamic IP)

  17. #17 Cain
    October 7, 2010

    Lyme is not a virus or bacteria or bug. Lyme is a town in Connecticut. That town has a disease named after it caused by Borrelia bacteria.

  18. #18 Brakeman
    October 7, 2010

    Simple! You simply sacrifice two perfect male pigeons and sprinkle their blood on an alter, while babbling in Hebrew to sky daddy. Haven’t you read the Bible?

  19. #19 titmouse
    October 8, 2010

    I thought it was IP blocking until I discovered that I could post using an old laptop from the same location/IP.

    I have not yet exhaustively tried posting from every half dead puter I own.

    BRB, trying husband’s…

  20. #20 titmouse
    October 8, 2010

    Ok on husband’s new puter at same IP as my previous post, which is trapped.

    Am I trapped?

  21. #21 alliouaga
    October 14, 2010

    Forgive me for pouring cold water, but the abstract of the paper we are all talking about says that the virus was found in the joints of only ONE patient . . . not quite enough to come up with whole vast new theories about Lyme, CFS, etc. etc.

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