A genetic defect protects mice from infection with Influenza viruses

December 5, 2013
This is an influenza virus, magnified by electron microscopy. Credit: HZI / Rohde

A new study published in the scientific journal PLOS Pathogens points out that mice lacking a protein called Tmprss2 are no longer affected by certain flu viruses. The discovery was made by researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig in collaboration with colleagues from Göttingen and Seattle.

Whether it is H1N1, H5N1 or H7N9: The flu virus influenza A exists in many different types as its two coating proteins haemagglutinin (HA) and neuraminidase (NA) can be combined in various ways. Theoretically, more than 100 different pairings are possible. Additionally, the coating proteins themselves can undergo changes. This variability is one of the reasons why the has to be renewed every year.

The virus uses haemagglutinin as a key to enter the host cell which is then captured to build new . To reach its final shape, the coating protein has to be cleaved by a molecular scissor. This is done by an enzyme of the infected host. Otherwise, the protein is not functional and the virus particles are not infectious. A variety of host enzymes, so-called proteases, that process the haemagglutinin have been identified using .

Scientists from the HZI have now been able to show how important those enzymes are for the progression of the infection. Mice with a mutation in the gene for the protease Tmprss2 do not become infected by containing haemagglutinin type H1. They are resistant against H1N1, the pathogen responsible for seasonal influenza epidemics, the "swine flu" and the "Spanish flu", which caused an epidemic in 1918. "These do not lose weight and their lungs are almost not impacted," says Professor Klaus Schughart, head of the Department "Infection Genetics" at the HZI. "Even though the virus still multiplies no active viral particles are formed which would infect the neighbouring cells." The infection is quickly terminated.

As the protease Tmprrs2 is a host factor it is an ideal intervention point for new drugs. So far, treatments, such as the well-known Tamiflu, attack parts of the virus. They have decisive disadvantages: The virus can become resistant and the therapy no longer takes effect. This problem does not occur when the medication intervenes with the metabolism of the patient. Furthermore, the mice Schughart and his team examined did not show any abnormalities. "We did not observe an obvious varied phenotype in these mice. They were neither impaired in their behaviour nor in their life expectancy. Presumably because other proteins are compensating for the lack of Tmprss2," says Dr Bastian Hatesuer, one of the scientists involved in the project. Blocking Tmprss2 for a short period could be a new therapeutic option as no strong side effects are expected.

Even though a drug like this is still a long way off, the observation is important for another reason: "Until now the dependence of virus production on proteases had only be demonstrated in cell cultures," says Schughart. "We are the first to show this in a living organism."

It is likely that there are humans having the same defect as the mice and who therefore may be resistant against specific flu viruses. This, however, remains unnoticed. "Because they don't get sick, they don't go to see a doctor," says Hatesuer. "Thus, they don't know that they are resistant."

Explore further: Food additive may prevent spread of deadly new avian flu

More information: Bastian Hatesuer, Stephanie Bertram, Nora Mehnert, Mahmoud M. Bahgat, Peter S. Nelson, Stefan Pöhlman, Klaus Schughart TMPRSS2 is essential for influenza H1N1 virus pathogenesis in mice PLOS Pathogens, 2013, DOI: 10.1371/journal.ppat.1003774

Related Stories

Food additive may prevent spread of deadly new avian flu

October 23, 2013
A common food additive can block a deadly new strain of avian influenza virus from infecting healthy cells, report researchers at the University of Illinois at Chicago College of Medicine in the online journal, PLOS ONE.

Stuck on flu: How a sugar-rich mucus barrier traps the virus—and it gets free to infect

November 23, 2013
Researchers at the University of California, San Diego School of Medicine have shown for the first time how influenza A viruses snip through a protective mucus net to both infect respiratory cells and later cut their way ...

Researchers suggest boosting body's natural flu killers

May 23, 2013
A known difficulty in fighting influenza (flu) is the ability of the flu viruses to mutate and thus evade various medications that were previously found to be effective. Researchers at the Hebrew University of Jerusalem have ...

Flu virus wipes out immune system's first responders to establish infection

October 20, 2013
Revealing influenza's truly insidious nature, Whitehead Institute scientists have discovered that the virus is able to infect its host by first killing off the cells of the immune system that are actually best equipped to ...

Research shows that anti-fungal medicine may increase vulnerability to influenza and other viruses

November 21, 2013
Scientists at the University of Massachusetts Medical School (UMMS) and the Wellcome Trust Sanger Institute have discovered evidence that a widely used anti-fungal medicine increases susceptibility to flu infection in mice ...

Recommended for you

Two lung diseases killed 3.6 million in 2015: study

August 17, 2017
The two most common chronic lung diseases claimed 3.6 million lives worldwide in 2015, according to a tally published Thursday in The Lancet Respiratory Medicine.

New test differentiates between Lyme disease, similar illness

August 16, 2017
Lyme disease is the most commonly reported vector-borne illness in the United States. But it can be confused with similar conditions, including Southern Tick-Associated Rash Illness. A team of researchers led by Colorado ...

Addressing superbug resistance with phage therapy

August 16, 2017
International research involving a Monash biologist shows that bacteriophage therapy – a process whereby bacterial viruses attack and destroy specific strains of bacteria - can be used successfully to treat systemic, multidrug ...

Can previous exposure to west Nile alter the course of Zika?

August 15, 2017
West Nile virus is no stranger to the U.S.-Mexico border; thousands of people in the region have contracted the mosquito-borne virus in the past. But could this previous exposure affect how intensely Zika sickens someone ...

Compounds in desert creosote bush could treat giardia and 'brain-eating' amoeba infections

August 15, 2017
Researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego and the University of Colorado Anschutz Medical Campus have found that compounds produced by the creosote bush, a ...

New malaria analysis method reveals disease severity in minutes

August 11, 2017
Left untreated, malaria can progress from being mild to severe—and potentially fatal—in 24 hours. So researchers at the University of British Columbia developed a method to quickly and sensitively assess the progression ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.