One of the scary things about filoviruses (eg Ebola, Marburg)… is that we dont know where they comes from. We know how polio is transmitted. We know how HIV-1 is transmitted. We know how influenza is transmitted. We know how rabies is transmitted.
Even if you dont have good vaccines or good therapies, if you know where a virus comes from or how it is transmitted, you can take steps to prevent illness.
One hypothesis is that small mammals are the natural reservoir. A way to look for that would be to study the immunology of lots of small mammals– Do they have intrinsic/innate defenses against these viruses, suggesting a co-evolution over time?
Um, some folks in Buffalo, NY did a bit better than that.
We detected integrated filovirus-like elements in the genomes of bats, rodents, shrews, tenrecs and marsupials. Moreover, some filovirus-like elements were transcribed and the detected mammalian elements were homologous to a fragment of the filovirus genome whose expression is known to interfere with the assembly of Ebolavirus. The phylogenetic evidence strongly indicated that the direction of transfer was from virus to mammal. Eutherians other than bats, rodents, and insectivores (i.e., the candidate reservoir taxa for filoviruses) were significantly underrepresented in the taxa with detected integrated filovirus-like elements. The existence of orthologous filovirus-like elements shared among mammalian genera whose divergence dates have been estimated suggests that filoviruses are at least tens of millions of years old.
This should not happen. Filoviruses are not retroviral, and they do not replicate in the nucleus. So:
1) a filovirus has to be in a germ line cell, MISTAKE
2) the virus needs to get its genome into the nucleus, MISTAKE
3) the virus needs to co-opt the reverse transcriptase activity of an endogenous retroviral element, MISTAKE
4) the filovirus cDNA needs to be integrated into the host DNA, MISTAKE
5) the cell where all of these mistakes are made needs to be successfully fertilized, carried to term, grow up, and have offspring
Wow. I guess in an infinite universe, anything can happen, but daaaaamn!
How did they go about finding these improbable miracles?
First, they did a simple tBLASTn search. Take an amino acid sequence you know (in this case, the Marburg NP gene) and look for nucleotides that code for that series of amino acids in any of GeneBanks uploaded sequences. And any hit that has a good ‘expect value’ means the sequences are the same, and its probably not by chance.
They found sequences in a handful of small mammals and marsupials.
To double-check their digital findings, they designed PCR primers to look for filovirus integration sites in the tammar wallaby, the little brown bat, and the big brown bat. The sequences were what they should be, and where they should be.
They even found that these genes were transcribed into RNA in some tissues! This might be by chance, but also possibly by design– these transcripts could act as RNA interference against real filovirus infections (which the authors hope will be investigated in the future), as some small mammals (mice and guinea pigs) are resistant to infection.
Now, the question many of you want an answer for– if this endogenization event is so rare, do the endogenous filovirus sites follow common descent?
Well, not all of the animals compared have appropriately detailed chormosomal maps to make that distinction, except for mice and rats:
A clear indicator of antiquity is the syntenous genomic location of a rat and mouse filovirus-like NIRV (Fig. 7A, B). These are the same copies that have a sister group relationship (Fig. 2). It is unlikely that integration of filovirus NP genes at the same genomic position occurred independently in rats and mice. The rat-mouse orthology provides a minimum date of NIRV formation at 12 to 24 MY[31, 32].
NIRV = non-retroviral integrated RNA viruses, heh.
But yes, NIRVs support common descent, just like ERVs. YAY!