杏吧原创

THE virus that causes AIDS is now being enlisted in the fight against the
disease. Researchers in Japan have shown that genetically engineered HIV can be
used to set a 鈥渂ooby-trap鈥� in the immune cells that are the target of the virus.
If these immune cells are then infected by the wild virus, they will commit
suicide, preventing the virus from spreading.

鈥淚 believe that this is the first attempt to kill HIV-infected cells using
recombinant HIV vectors,鈥� says Takashi Shimada of the Center for Advanced
Medical Technology at Nippon Medical School in Tokyo. 鈥淭his strategy should be
highly useful for treating HIV infection.鈥�

Shimada and his colleagues say that their technique should be useful for the
long-term control of the disease. They have created a form of HIV that carries a
鈥渟uicide gene鈥� called HSV-TK. This codes for an enzyme that turns an
inactive 鈥減rodrug鈥�, ganciclovir, into a highly toxic form.

The idea is to use the engineered virus to alter the immune cells of people
with HIV and then give them regular doses of ganciclovir. The great advantage of
using HIV to deliver the suicide gene is that it will target exactly the same
immune cells as the wild virus.

Crucially, however, the gene is linked to a promoter that only the wild virus
activates. This means it will lie dormant in uninfected cells. But if the cells
are infected with wild HIV, the gene will be activated, converting the
ganciclovir into the toxic form and killing the cells before the virus can
spread.

The researchers have shown that their technique can prevent wild HIV
spreading among human immune cells grown in culture. They have now started a
preclinical study in mice carrying human immune cells. 鈥淚 would like to apply it
to the treatment of humans in the near future,鈥� Shimada says.

The team also discovered that when the booby-trapped cells are infected with
wild HIV in the absence of the prodrug, the suicide gene can be repackaged to
form more viral vectors that can booby-trap other immune cells. Normally, it鈥檚
not considered safe for gene therapy viruses to be able to replicate inside the
human body. 鈥淏ut with HIV-positive people, HIV is already in the body and
replicating, so why not,鈥� comments Manuel Caruso of the University Hospital of
Quebec in Canada, who has worked on putting the HSV-TK suicide gene
into immune cells using vectors other than HIV.