In a breakthrough that could potentially lead to a cure for HIV
infection, scientists have discovered a way to remove the virus from
infected cells.
The scientists engineered an enzyme which attacks the DNA of the HIV
virus and cuts it out of the infected cell, according to a study
published today in the U.S. journal Science.
The enzyme is still far from being ready to use as a treatment, the
authors warned, but it offers a glimmer of hope for the more than 40
million people infected worldwide.
Cut it out
“A customized enzyme that effectively excises integrated HIV-1 from
infected cells in vitro might one day help to eradicate (the) virus
from AIDS patients,” Alan Engelman, of Harvard University’s Dana-Farber
Cancer Institute, in Boston, U.S., wrote in an article accompanying the
study.
Current treatments focus on suppressing the HIV virus in order to
delay the onset of AIDS and dramatically extend the life of infected
patients. What makes HIV so deadly, however, is its ability to insert
itself into the body’s cells and force those cells to produce new
infection.
“Consequently the virus becomes inextricably linked to the host,
making it virtually impossible to ‘cure’ AIDS patients of their HIV-1
infection,” Engelman explained.
That could change if the enzyme developed by a group of German
scientists can be made safe to use on people. That enzyme was able to
eliminate the HIV virus from infected human cells in about three months
in the laboratory.
The researchers engineered an enzyme called Tre which removes the
virus from the genome of infected cells by recognizing and then
recombining the structure of the virus’s DNA.
This ability to recognize HIV’s DNA might one day help overcome one
of the biggest obstacles to finding a cure: the ability of the HIV
virus to avoid detection by reverting to a resting state within
infected cells which then cease to produce the virus for months or even
years.
“Proof of principle”
“Numerous attempts have been made to activate these cells, with the
hope that such strategies would sensitise the accompanying viruses to
antiviral drugs, leading to virus eradication,” Engelman wrote.
“Advances with such approaches in patients have been slow to
materialize.”
New experiments must be designed to see if the Tre enzyme can be used to recognize these dormant infected cells, he wrote.
“Although favourable results would represent perhaps only a baby
step toward eventual use in patients, the discovery of the Tre
recombinase proves that enzymatic removal of integrated HIV-1 from
human chromosomes is a current-day reality,” he said.
The researchers who developed the enzyme were optimistic about their
ability to design additional enzymes which would target other parts of
the virus’s DNA.
However they warned that there were significant barriers to overcome before the enzyme could be used to help cure patients.
“The most important, and likely most difficult, among these is that
the enzyme would need efficient and safe means of delivery and would
have to be able to function without adverse side effects,” wrote lead
author Indrani Sarkar of the Max Planck Institute for Molecular Cell
Biology and Genetics in Dresden.
“Nevertheless the results we present offer an early proof of
principal for this type of approach, which we speculate might form a
useful basis for the development of future HIV therapies,” Sarkar
concluded.