DNA in the Cell - "Ahhh! Kill it!"

Viruses are tricky buggers - they force their way into another organism's cell and hijack its machienery to utilize for their own nefarious purposes. This is clearly pretty harmful for the host so there's been pretty strong evolutionary pressure to develop ways to stop them or slow them down (hence the immune system). But in order to do anything, the host first has to recognize that it's infected.

This isn't necessarily as straightforward as it might seem. Viruses (and bacteria and fungus and protists and worms etc) are living things, and use the same molecular building blocks, and many of the same biological processes as our own cells. But there are enough differences that evolution has crafted specialized receptors that can notice some invader lurking somewhere it doesn't belong. These receptors, broadly called "pattern recognition receptors" (PRRs), can bind onto particular molecular patters and once bound, signal to the cell that something is wrong and that action must be taken. I study a class of PRRs called Toll-like receptors, which are present on specialized immune cells like macrophages, and induce a broad range of effects like phagocytosts (cell eating), inflammation and adaptive immune system activation, all geared at pathogen clearance.

But all cells, not just the ones in the immune system, have a way to recognize if they themselves are infected with virus. There are PRRs inside the cell that can recognize viral genomes - the RNA and DNA - once a virus pops off its coat and actually starts going about the business of infection. We've known about some of the RNA sensors for a while, but the DNA sensor(s) have remained elusive.

The first candidate was different paper that purports to have discovered another DNA sensor called IFI6. Whether that's the one seeing the HIV genome, or whether there are still more to be discovered remains to be seen.

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I enjoy your posts.

By disenchantedme… (not verified) on 03 Nov 2010 #permalink

If TREX1 degrades HIV DNA it should deactivate the virus, but what you wrote implies that it allows HIV to evade cellular interferon response. So why is HIV not deactivated by TREX1 cutting up it's genome?

Al - that's an excellent question. Actually, I would guess that one of the points of TREX1 in general is to try to chew up virus DNA before it can cause an infection. I don't have a good explanation, but HIV has clearly evolved to make just enough of its DNA genome to get around TREX1 and get integrated into the host cell, but not enough to trigger DNA sensors.

Viruses are sneaky, and they're better at life than we are.

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