Dawn of the deadly bug � it's baaack

Respiratory virus hides out in the lungs, re-infecting kids months later

By Owen Dyer

Respiratory syncytial virus (RSV) is a master of disguise in the microbial world. The insidious infection hits hard and then just disappears. But just when the unsuspecting victim is lulled into complacency, it strikes again. So how does this potential killer manage to give the immune system the slip? And where does it hide out? British investigators are hot on the trail.

RSV seems remarkably unphased by even healthy immune systems. New infections keep cropping up even in patients who already have antibodies against the disease. Researchers speculate that these new infections might not be due to re-exposure to RSV, but to the fact the virus never left.

Some of the strategies RSV uses to evade the immune system are already known. For one thing, it manufactures proteins that fight the antiviral effects of interferon, which normally interferes with the virus's replication. It can also change its shape so that neutralizing antibodies can no longer recognize it. The question is, does such sneakiness allow RSV to persist for years in vivo, and if so, is that a possible explanation for the link between early childhood RSV infection and later chronic wheeze?

The answer was published in the April edition of the American Journal of Respiratory and Critical Care Medicine.

Since it would be unethical to infect children with RSV, the researchers infected genetically engineered mice with human RSV. They found that after 14 days, the virus could no longer be found in samples taken from the airways, but that telltale traces of the virus's genetic material were still lying dormant in lung tissue over 100 days later. By temporarily suppressing the immune system, the researchers were able to recover infective virus after 150 days.

Because the latent viral genome that was recovered was largely unmutated, and because neutralizing antibody and memory cytotoxic T cell responses remained intact in these mice, lead author Professor Peter Openshaw of Imperial College, London suggests that "RSV is a 'hit and hide' virus, rather like HIV, herpes or some hepatitis viruses. The symptoms seem to go away but the virus is just hiding, waiting for a chance to re-emerge and begin infecting other people."

In an accompanying commentary, Dr Ralph Tripp of the Centers for Disease Control in Atlanta, Georgia, proposes leukocytes and the neurons that innervate lung tissue as likely candidates for RSV's hiding places. But he's less sure than the authors that viral mutation plays no role in persistence. Nevertheless, Dr Tripp feels the results may throw light on other persistent viruses. The results, he said, "provide further evidence that viruses that are minimally or non-cytopathic in vivo often establish persistent infections in their hosts despite initial control by cytotoxic T lymphocytes."