Norovirus Interacts with Gut Bacteria to Establish a Persistent Infection That Can Be Blocked by Interferon Lambda

A team of molecular microbiologists and virologists has found that norovirus requires an intimate interaction with certain gut bacteria to establish a persistent infection, and that the infective process can be blocked by the immune factor interferon lambda (INFlambda).

Norovirus causes more than 90% of global epidemic nonbacterial gastroenteritis, and it is thought to be spread by a subset of people who maintain a low-level persistent infection. How the enteric virus establishes such persistent infections is not well understood.

Investigators at Washington University School of Medicine (St. Louis, MO, USA) have turned up some interesting new insights regarding how norovirus infection becomes established and is maintained. They reported in the November 27, 2014, online edition of the journal Science that establishment of the viral infection in a mouse model depended on interaction with certain gut bacteria and that the infection could be prevented by treatment with antibiotics. Viral infection could be established following replenishment of the bacterial microbiota. Antibiotics did not prevent tissue infection or affect systemic viral replication, but acted specifically in the intestine.

In a second paper in the same issue of the journal Science, the investigators reported that while the cytokines interferon alpha (IFNalpha) and interferon beta (IFNbeta) prevented the systemic spread of norovirus in the mouse model, only IFNlambda controlled persistent enteric infection. Infection-dependent induction of IFNlambda was governed by the viral capsid protein and correlated with diminished enteric persistence. Treatment of established infection with IFNlambda cured mice in a manner that required non-hematopoietic cell expression of the IFNlambda receptor, Ifnlr1, and was independent of adaptive immunity.

“I believe that is a new concept in immunology,” said senior author Dr. Herbert W. Virgin, professor of pathology and immunology at Washington University School of Medicine. “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 virus actually requires the bacteria to create a persistent infection,” said Dr. Virgin. “The virus appears to have a symbiotic relationship with the bacteria — they share the job of establishing persistence. We need a much more detailed understanding of how antibiotic treatment affects the links among host, bacteria, and virus.”

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Washington University School of Medicine