A COMMON virus that can reduce lifespan and cause blindness has been cleared from human blood for the first time.
Cytomegalovirus
(CMV), a type of herpes virus, is carried by about 70 per cent of
people and, although it usually doesn't cause illness, shaves 3.7 years
off life expectancy.
In people with a weakened immune system,
however, the virus awakens and can cause serious illness and blindness.
This can be a particular problem if the only available donor for a bone
marrow transplant is infected with CMV and the recipient is not.
CMV only expresses a handful of genes when it is dormant. One of them is UL138.
To investigate what it does to cells, Michael Weekes at the University
of Cambridge and colleagues grew healthy human cells alongside cells
that were made to express UL138 in the presence of labelled amino
acids – the raw ingredients used to make proteins. They then used mass
spectrometry to identify how UL138 changed the cells' expression of proteins.
"We know that viruses remodel the
landscape at the surface of the cell, so we've been asking 'what
proteins are on the cell surface and how does CMV change that?'" says
Paul Lehner, also at Cambridge, who supervised the work. CMV appears to
dampen the production of a protein called MRP1 that pumps toxic
chemicals out of cells – including the cancer drug vincristine. If
infected cells can no longer pump out vincristine, perhaps this would
kill them while sparing healthy cells that remove the poison?
To find out, the team took blood samples
from 15 volunteers with CMV, treated the samples with vincristine and
then reactivated the virus. "We either dramatically reduced or
eliminated our ability to [detect] any virus," says Lehner, who
presented the results at the Strategies for Engineered Negligible
Senescence conference in Cambridge this month.
"It will be fascinating to see how this new method comes to be applied in clinical practice," says Paul Moss
of the University of Birmingham, UK. Vincristine can have severe side
effects, so is unlikely to be used to clear CMV in healthy people or
transplant patients. However, it could be used to treat donor blood or
stem cells from bone marrow before transplantation.
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