Lentivirus Saves Lives

The news is out that HIV-derived lentiviruses are saving lives. Like the Human Improvement Vector in The Highest Frontier we see lentiviruses (now called lentivectors) carry life-saving genes into human genomes. A decade before, the intelligent AZ-loving micros in Brain Plague prefigured this possibility.

What makes lentivectors so promising is precisely the property that makes HIV so deadly: Its ability to insert in a human genome and stay there forever. And somehow (this part we don’t yet understand) the chance of disrupting the host genome, or causing cancer, appears less than for other vectors.

How does it work? In a nutshell, here’s how HIV infects a cell.  (For the mind-boggling details, see our textbook, Microbiology: An Evolving Science.)

The HIV virion enters the cell, comes apart and copies its RNA into DNA, which then integrates at a spot in the human cell’s genome. (In the case of the girl with leukemia, they took her T-cells out first, then infected them with the lentivector. In the case of the boys with adrenoleukodystrophy, they infected his bone-marrow CD34+ stem cells.)

But how do we avoid HIV causing AIDS?
Here is the HIV viral genome:

The vector is heavily engineered: All the disease-causing genes were cut out. This is called a “gutted vector.”

In the gutted middle, we then place the key genes needed to help the host; in the case of the girl with leukemia, this was a gene directing the T-cells to kill the cancer cells. In the case of the boys with ALD, it was a gene replacing their defective enzyme.

So if you remove the HIV disease genes…how does the vector still infect and insert its genome?  Well, here is where it gets interesting. You have to put key disease genes on “helper plasmids” that briefly express the infection genes, then disappear. And you add all sorts of odd viral control sequences to fine-tune the infection.

My favorite is that woodchuck hepatitis virus regulator site–I have no idea how they came up with that one. It’s a Frankenstein business, to be sure. But we’re saving lives.

BTW the CDC recently recommended that we all get tested for HIV, because “test and treat” is the way to wipe it out. We know how to wipe out HIV in the wild; it just takes money and the will to do so. And someday, lentiviruses will be known as lifesavers. (With a little help from woodchucks.)