Retroviruses cause cancer.
Like how HPV causes cancer, its not really 'on purpose', its just a side-effect of their life-cycle-- insert DNA randomly into a genome enough times, and eventually youre going to plop somewhere you aint supposed to be, and cause cancer.
Thus I am terribly amused when Creationists bawww about how ERVs are perfect and special (not junk!)... cause if those ERVs werent rendered junk by mutagenesis or epigenetics, we would all be dead (technically, never born).
Found a paper in Nature Cancer Gene Therapy that kinda turns this issue upside down:
Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer
Theyre exploring ways to use envelope (from ERVs and retroviruses) to kill cancer!
Heres what they did--
Know how we got HeLa cells? There are lots of other cell lines we use in the lab that we got this way too. One of those is H322. Its a cell line we got from a fellow with lung cancer in 1981 (his cancer cells have been multiplying in labs for almost 30 years).
If you inject these cells into mice with no adaptive immune system, the mice get this 'human' cancer.
One of the features of this cancer is that it takes up exogenous DNA (!!!). So instead of needing a virus to deliver the genes youre interested in, you can just inject these mice with DNA, and the tumor will suck it up all on its own (again, !!!).
So, they injected the mice with DNA that contained different retroviral envelope genes. Once this DNA is in the tumors, the tumor will start making the envelope proteins. What does envelope like to do?... SYNCYTIA!!
Cells expressing Env fuse with surrounding cells, and they fuse with surrounding cells, on and on till you get 50-100 nuclei in one big cell... and then it dies. They also spit out stuff that kills surrounding cells (bystander effect), which is kinda just fine when youre talking about a tumor.
Their treatments didnt totally obliterate the tumors, but in the absence of any chemo/radiation, they stopped/slowed the tumors growth. This could end up being another weapon in our arsenal against some kinds of cancers (this only worked because of features of H322, not all lung cancers will have these features).
An unexpected, really neat weapon!
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I'm probably missing something completely obvious here, but why is that? The "and then it dies" part, I mean.
"I'm probably missing something completely obvious here, but why is that? The "and then it dies" part, I mean."
I would *guess* it essentially just explodes the cell... like if you were to try and shove too many marbles into a ballon.
Excellent article. I love things like this. I hope eventually, more people will take the time to read stuff like this because it's just amazing and if people heard more about this stuff, they'd fund science more.
Of course there are lots of ideas, and some of these ideas pan out for some kinds of syncytia and not others... we still dont know.
So if youre missing something obvious, we are all missing it :)
Abbie, I read that syncytia might become unstable, for one thing, because the state of being a syncytium amplifies apoptotic signals (Scheller et al., and because (maybe) of chromatin condensation. Confined spaces also tend to increase apoptosis rates of syncytia (Ferri et al.).
"why is that? The "and then it dies" part, I mean."
My first guess was that when they get too big they might have trouble with nutrient and gas exchange and that their cellular organisation would be all messed up.
But apparently syncytia are not necessarily passive blobs, the ones induced by HIV may be pretty frisky, crawling around the body with their giant pseudopods *creeps*
(What's the latest on this theory, Abbie? Most of the articles talking about the importance of giant crawly syncytia in HIV seem to be from the '90s.)
windy-- With HIV-1, syncytia formation is really more of a lab trick than something patients should be worried about. SUPT1s are another cell line we use a lot, like the TZM-bls?
Back in the day (1990s) they used this trick to phenotypically describe HIV-1 variants (little pdf linky).
Well. ERV is perfect.
Just as a guess, windy might be on the right track. High glycolytic rates [Warburg effect] could produce high acidity in the interior of the syncitia, initiating apoptosis.
Maybe if a virus is going to inject its genome in a cell that it could stand to benefit by injecting it into some oncogene.
I mean of course selection won't favor them injecting into genes that will kill the cell because it knocks out essential genes. That would be the classic case of a parasite killing its host.
However it could stand to benefit by disrupting the cell division and apoptosis genes. That way there's a higher chance that the host cell will linger from not be able to respond to apoptosis cues. Keeping the host cell alive could be a benefit.
If there were even a slight shift in specificity from genes that are kind of okay to knock out, and genes that actually benefit the cancer virus
You could get a virus that favors oncogenes and then every once in a while it gets stuck