Viruses can outsmart the immune system. Image via Shutterstock.com
Our
immune systems are equipped with “natural killer” (NK) cells that
recognize and eliminate influenza-virus-infected cells in order to keep
the virus from spreading.
If
NK cells always worked perfectly, nobody would get sick with the flu.
Obviously, something can go wrong because many people do get flu.
Israeli doctoral student Yotam Bar-On tackled this mystery, and his
findings could lead to a whole new way of treating this sometimes deadly
viral infection.
“A
few years ago, my supervisor, Prof. Ofer Mandelboim, discovered that NK
cells are important in fighting flu infection,” Bar-On tells ISRAEL21c.
“However, when we infected mice with influenza virus, we found that the
virus can manipulate the NK cells and evade getting killed. The NK
function is not 100 percent because the influenza fights back.”
In
their lab at the Hebrew University of Jerusalem, Bar-On and Mandelboim
were able to identify the weapon that the virus uses to battle the
body’s natural killers: It’s a protein called neuraminidase, and it
effectively neutralizes receptors on the NK cells that are responsible
for detecting influenza-virus-infected cells.
As they reported in an article published in the journal Cell Reports, the flu virus uses neuraminidase to cut the function of NK cells to about 50% of their normal effectiveness.
PhD student Yotam Bar-On is seeking a new way of treating the flu. Photo courtesy of the Hebrew University
“Most
interestingly, when we inhibited the neuraminidase we noticed the NK
worked better, and the mice actually recovered from the flu,” says
Bar-On. “So we proved the ability to defend against the influenza virus
by inhibiting this protein.”
Overcoming resistance to treatment
Emergence
of new influenza strains, such as the avian flu (H5N1) and swine flu
(H1N1), lead to severe pandemics across the world. Recently, a deadly
avian influenza strain (H7N9) in China caused the death of six people in
one month. Medical experts are frustrated that many flu strains have
become resistant to existing antiviral drugs.
Bar-On
and Mandelboim’s discovery sets the tone for developing new treatments
to help the immune system’s natural killer cells do their job better.
“Right
now, existing drugs work to inhibit a different protein in the flu
virus to inhibit the spread of the virus, but their disadvantage is that
the virus can mutate and evade the effects of the drug,” Bar-On
explains. “You then get a resistant strain.”
The
Israelis’ idea is to inhibit neuraminidase in order to allow the NK
cells to function at full strength. “It will be much harder for the
virus to evade this new kind of treatment,” says Bar-On, 30. “Under the
supervision of Prof. Mandelboim, I am now working on a more practical
approach to develop such a drug.”
Mandelboim,
a professor of general and tumor immunology at the Institute for
Medical Research Israel Canada (IMRIC) at the Hebrew University Faculty
of Medicine, recently won a joint grant from the Juvenile Diabetes Research Foundation and the Israel Science Foundation for
his work with Angel Porgador of Ben-Gurion University of the Negev to
develop an antibody that would block a receptor used by NK cells to
destroy insulin-producing cells in the pancreas.
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