A new* virus was recently discovered in my parents backyard, so to speak. Pop-sci articles:
Heartland Virus: New Phlebovirus Found in Missouri
Actual journal article:
A New Phlebovirus Associated with Severe Febrile Illness in Missouri
... and its NOT MY FAULT. Proof? It is apparently a new phlebovirus, and I know absolutely nothing about these guys.
The phlebovirus genome is made up of three strands of negative sense RNA--- that is its genome is broken up into three parts, and backwards. It has to use a virally encoded RNA-RNA polymerase (humans do not ever make RNA from RNA, so it is not a protein this kind of virus can steal from its host) to turn its genome into the kind of RNA template that can be used to make lots and lots of viral messenger RNA, to make lots and lots of viral proteins.
Unlike retroviruses, phleboviruses do not ever have to go anywhere near the host cell nucleus. To infect a cell, the virions get endocytosed by the host cell into a vesicle, and then the viral RNA is released into the cytoplasm. And thats where all of the action occurs-- generation of the RNA, generation of proteins, and assembly. Phleboviruses do not appear to want much from their host at all, except for the ribosomes.
Just to be clear, this virus is not 'new' in the sense we have never seen it before, or 'new' in the sense it has never infected humans before. Phleboviruses do infect humans, and we have known that for a long time. What is different about *this* virus, is that it is not a phlebovirus we already knew about (it is related to the others, but not similar enough that we would just give it one of the old names), and we have never seen this kind of virus in the Western hemisphere before.
And now it shows up on some farms in Missouri.
Two farmers in 2009* came down with a similar, odd illness-- fever (but nothing crazy high), headache, fatigue, diarrhea, fairly standard viral fare (though also possibly an enteric bacterial infection). What was 'weird' for Missouri and viruses/bacteria is that they also had extremely low platelet counts and extremely low white blood cell counts. It obviously wasnt a regular ol norovirus or E. coli infection.
So they sent some blood samples off to be tested-- after culturing the patient samples with some potential target cells, they found a virus. Not in the XMRV sense (they 'found' a virus after passaging (read: contaminating) cells over and over and over and over and then epigenetically modifying host cells to induce ERV expression), but like, they found VIRUS:
A New Phlebovirus Associated with Severe Febrile Illness in Missouri, NEJM 2012
It doesnt take the trained eye of a virologist to see there are viruses EVERYWHERE in this pic.
So these folks sequenced the genome of this virus and it turns out it is similar to phleboviruses, and as of 2011, the patients have antibodies that are highly reactive to phleboviruses. These scientists are calling this new guy 'Heartland Virus', and they think it is spread by tick bites. None of this is 'proven' yet, in the sense no one has loaded a tick full of the Heartland Virus, stuck it on some people, and waited until the people got sick, but considering the genomics, virology, and epidemiology of other phleboviruses, they are pretty sure that this is whats going on.
A nice little reminder that in a global society, zoonotic events, emerging infectious diseases, they arent just for the jungles of Asia or Africa. They can happen right here in the Heartland.
*By 'new' I mean that these two cases occurred in 2009, and we are just now hearing about it. ??? O.0
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"humans do not ever make RNA from RNA"
Never say never =P
hTERT and our mitochondrial RNA processing endoribonuclease have been shown to be able to interact and form a functioning RNA-dependent RNA Polymerase in humans that generates dsRNAs which are processed into siRNAs via Dicer.
The plot thickens...
"Scientists at the Centers for Disease Control and Prevention think the men were infected by lone star ticks, meaning that there may be a frightening new addition to the list of tick-borne dangers that includes Lyme disease, babesiosis and Rocky Mountain spotted fever. But despite scouring the countryside, investigators have found neither ticks nor animals carrying the new virus. They have named it the Heartland virus, for the hospital and region where it was found. So far, the two men in Missouri are the only humans known to have been infected."
New Virus Tied to Ticks Poses Puzzle for Doctors
Ah, those funny Bunyaviruses. We have Schmallenberg right now.
BTW, negative strand viruses don't make RNA to use as a template, but make mRNA directly after fusion. Transkription comes first, Replication second. The genome is the mRNA template.
@ Poodle stomper: Fuck, really? does it function in telomere silencing? paper?
I'm not sure off the top of my head if the RDRP activity is restricted to telomere sequences... I want to say it isn't but I'm not certain.
"An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA."
Nature. 2009 Sep 10;461(7261):230-5. Epub 2009 Aug 23. Maida Y, Yasukawa M, Furuuchi M, Lassmann T, Possemato R, Okamoto N, Kasim V, Hayashizaki Y, Hahn WC, Masutomi K.
Also a review (from 2011)
"RNA-dependent RNA polymerases in RNA silencing." Biol Chem. 2011 Apr;392(4):299-304. Epub 2011 Feb 7. Maida Y, Masutomi K.
My first post with links is in moderation (probably the whole multiple URLs thing) but to add to it, if it does function in telomere silencing (not sure there), it isn't restricted to that as it can extend non-telomere RNAs from an RNA template that are not telomeric (according to Kenkichi Masutomi). In case my other post didn't actually send (also possible) reference papers include:
"RNA-dependent RNA polymerase in RNA silencing." Biological Chemistry
"An RNA dependent RNA polymerase formed by TERT and the RMRP RNA" Nature 2009; 461: 230-235
Thanks for saying something, Poodle! Your comment didnt get put in moderation, it got trashed! Now Im going to have to start checking the bin now and then-- That cant be the first time this happened :(
It's OK, ERV. I'm used to ladies trying to ignore me. Story of my life ;-)
Thanks to both of you!
Plants, C.elegans, fungi and probably Drosophila have a "real" cellular RdRP with another structure than TERT-RMRP BTW.
Neat! What's the advantage for them in having this? Is it just used in RNAi or something else, too?
They use external and internal RNAs to make siRNA and use those for systemic RNAi. When you want to knock down something in C.elegans, you express it as dsRNA in E. coli and feed them to the worms. The intestinal cells take up the RNAs, multiply them and spread them in the organism and that causes a systemic knock down.
This functions in antiviral defense, most probably in plants, which can shuttle RNAs through plasmodesmas.
There is a huge literature for C. elegans on this.
Post in moderation / trash bin.
the 2009 Drososophila paper is especially relevant for this virology blog :)