Common virus hides in immune cells: Experts

By Lidia Wasowicz

PALO ALTO, California (UPI): A virus so common it affects nearly 100 percent of some of the world's populations and so dangerous it can prove lethal hides in cells basic to the disease-fighting immune system, researchers said last week.

Reporting in the Proceedings of the National Academy of Sciences, the investigators said they found genes of latent cytomegalovirus, or Cmv, in white blood cell progenitors in human bone marrow -- a discovery that could lead to a vaccine against the ubiquitous microbe.

"This usually innocuous virus resides in some of the most important cells in the human body -- granulocyte-macrophage progenitors, or Gm-Ps, the parents of important white cells crucial to the immune response," said lead study author Edward Mocarski of Stanford University. "We had suspected that white- cell precursors would be involved, but no one had any understanding of what genes Cmv might produce in the latent period there."

A member of the ancient and complex herpesvirus family, Cmv infects nearly 100 percent of some populations around the world, being transmitted before or at birth and later through saliva, blood, urine and sexual contact.

Initial symptoms remain mild, followed by a period of harmless latency in most healthy people.

"But the virus can cause birth defects in a developing fetus and life-threatening disease in children and adults with weakened immune systems, such as people with Acquired Immune Deficiency Syndrome, or AIDS, premature infants and organ transplant recipients," Mocarski said.

So long as the host remains healthy, Cmv -- which has been around for millions of years -- does little harm. But if the immune systems lacks maturity or normal strength, Cmv can cause a range of potentially fatal diseases.

Antiviral drugs can slow -- but not stop -- damage from the reactivated virus, Mocarski said.

The mystery has been how the virus sleeps and awakes. Studies to clarify the matter have been confounded by the viruses' extraordinary complexity. Rather than the three or so genes of simpler viruses, this villainous microorganism boasts 230.

"The large genome and the large number of genes carried by Cmv, combined with the complexity of cell types that might be involved in acute and in latent infection, presented formidable obstacles to understanding the biology of this virus," Mocarski said.

Since genes responsible for the virus's growth shut down during latency, the researchers focused on genes that remain active by infecting a mixture of cells in a test tube.

"We found these cells were able to carry the viral genome without being damaged themselves, and we detected unique genes that were active then," Mocarski said.

Next, the scientists identified the unique genes as Cmv latency-associated transcripts, or Clts, and set out to discover the type of cells in which they hide.

"We found a latent infection marker in five of seven marrow samples from individuals infected with Cmv," said study co-author Dr. Kazuhiro Hondo, now an associate professor at Osaka University Medical School in Japan.

"This provided further evidence the genes we had discovered were bona fide, because they appeared in a naturally occurring latent infection. It also provided evidence that white cell progenitors can be a major source of reactivated Cmv, which can lead to disease in transplant recipients."

Faced with critical tissue shortages, doctors sometimes knowingly use Cmv-infected tissues in transplant recipients.

"Now that we can measure the quantity of latent Cmv in tissues, we might begin to exclude donors with the highest levels of infection, reducing the risk of severe Cmv disease in recipients," said Dr. Karl Blume, professor of medicine and director of the Stanford Hospital Bone Marrow Transplantation Program.

"Also, knowing the level of infection in the donor tissue will help clinicians more effectively protect the recipients against Cmv disease, possibly through the use of antiviral drugs."