Washington University. US: Antibiotics aren’t supposed to be effective against viruses. But new
evidence in mice suggests antibiotics may help fight norovirus, a highly
contagious gastrointestinal virus, report scientists at Washington University School of Medicine in St. Louis.
The researchers found antibiotics could help prevent norovirus
infections. The same team also showed that a recently identified immune
system molecule can cure persistent norovirus infections even in mice
with partially disabled immune systems. The surprising findings,
available online in Science, will appear Jan. 16 in the journal’s print
edition.
Outbreaks of norovirus are notoriously difficult to contain and can
spread quickly on cruise ships and in schools, nursing homes and other
closed spaces.
The researchers found that norovirus works its way into gut tissue in
mice that have been pretreated with antibiotics but that the virus
cannot establish a persistent infection. Follow-up studies showed that
norovirus needs a bacterial collaborator to establish a persistent
infection in the gut. Eradicating the bacterial partner with an
antibiotic can prevent persistent norovirus infection in mice.
“The virus actually requires the bacteria to create a persistent infection,” said senior author Herbert W. Virgin
IV, MD, PhD, the Edward Mallinckrodt Professor of Pathology and head of
the Department of Pathology and Immunology. “The virus appears to have a
symbiotic relationship with the bacteria — they share the job of
establishing persistence.”
No studies have indicated that animals or insects carry and spread
human norovirus. Therefore, scientists suspect that the sources of
outbreaks may be people who have persistent norovirus infections but
don’t have symptoms, such as stomach pain, nausea, diarrhea and
vomiting. Virgin and his team decided to explore this possibility by
studying a mouse model of chronic norovirus infection.
In additional tests, the scientists found they could restore the
norovirus infections by transplanting fecal material from untreated mice
into mice that earlier had been treated with the antibiotics. The
transplants contained the bacteria eliminated by the antibiotics.
The scientists also looked for mouse proteins essential to preventing
chronic norovirus infections. They found that a receptor protein for an
immune inflammatory factor known as interferon lambda was required for
antibiotics to prevent infection. Giving the mice interferon lambda also
prevented norovirus infection, suggesting it also should be evaluated
as a treatment for norovirus.
In the second study, the Washington University researchers reported
that treatment with interferon lambda offers a significant advantage: It
not only prevents the start of persistent norovirus infections but also
eliminates established persistent infections. This was true even in
mice lacking immune cells that scientists thought were essential to
eradicating viral infections.
“I believe that’s a new concept in immunology,” said Virgin. “We
thought that interferon lambda and other related molecules in the immune
system could only contain viral infections until other parts of the
immune system, including antibodies and T cells, finished the job.”
The researchers speculated that other viruses and bacteria may form similar symbiotic partnerships in humans.
“We need a much more detailed understanding of how antibiotic
treatment affects the links among host, bacteria and virus,” Virgin
said.
The research is supported by the National Institutes of Health (NIH),
grants R01 AI084887, 5T32CA009547, 5T32AI007163, 1F31CA177194, U19
AI083019, U19 AI106772, F31CA177194-01; the Crohn’s and Colitis
Foundation Genetics Initiative, 274415; the Broad Foundation, IBD-0357;
the Cancer Research Institute; and the American Cancer Society.
Baldridge
MT, Nice TJ, McCune BT, Yokoyama CC, Kambal A, Wheadon M, Diamond MS,
Ivanova Y, Artyomov M, Virgin HW. Commensal microbes and interferon
lambda determine persistence of enteric murine norovirus infection.
Science, online Nov. 27, 2014; in print Jan. 16, 2015.
Nice TJ,
Baldridge MT, McCune BT, Norman JM, Lazear HM, Artyomov M, Diamond MS,
Virgin HW. Interferon lambda cures persistent murine norovirus infection
in the absence of adaptive immunity. Science, online Nov. 27, 2014; in print Jan. 16, 2015.