A Natural Vaccine?

One of the hottest trends in immunology--injecting DNA as a vaccine--may actually have been invented millions of years ago. In tomorrow's Nature, a team led by immunologist Rolf Zinkernagel from the University Hospital in Zurich, Switzerland, suggests that animals may gain lifelong immunity to some viral infections by retaining a bit of viral DNA inside their cells like a souvenir.

After the body has defeated a viral or bacterial invasion, the immune system usually starts losing its memory of the attacker as the last invaders fade away. Yet, after mice have beaten an infection with the lymphocytic choriomeningitis virus (LCMV), they remain immune--even long after the virus has vanished from their bodies. The Swiss team decided to check the mouse spleen cells for a possible long-term remnant of the infection: viral-looking DNA. To look for DNA was perhaps, as Zinkernagel puts it, "a crazy idea," because LCMV doesn't produce DNA at all; like many other viruses, it uses the slightly different RNA to perpetuate its genetic information.

To their surprise, the team did find DNA "copies" of viral RNA in mouse cells until at least 225 days after infection. The copies were made from RNA by the enzyme reverse transcriptase (RT), since an RT inhibitor blocked viral DNA production in infected cells. Perhaps, the Swiss team suggests, the animals use RT to make the viral DNA, in order to keep their immune systems alert after the virus is gone. This idea was bolstered by the finding that viral DNA production also took place in cells from another natural LCMV host, the hamster, but not in human, monkey, dog, or cow cells, which are not susceptible to the virus.

The finding is "very original and a lot of fun," says Jaap Goudsmit, a virologist at the Academic Medical Center in Amsterdam. However, he notes that Zinkernagel hasn't yet proven that the DNA is the cause of the mice's immunity. To do that, the team would have to show that DNA is actually translated into a protein, which in turn has to trigger an immune response. But even without that evidence, Goudsmit says, "It's a lovely experiment."