Study reveals new therapeutic target for slowing the spread of flu virus

June 22, 2018, Perelman School of Medicine at the University of Pennsylvania
Flu shot. Credit: NIAID

Influenza A (flu A) hijacks host proteins for viral RNA splicing and blocking these interactions caused replication of the virus to slow, according to new research published in Nature Communications by Kristin W. Lynch, Ph.D., chair of the department of Biochemistry and Biophysics in the Perelman School of Medicine at the University of Pennsylvania, and doctoral student Matthew Thompson. Their results also suggest that infection with flu A may reduce splicing of some host genes, which could point to novel strategies for antiviral therapies.

Influenza A is a common human pathogen that causes 250,000 to 500,000 deaths per year worldwide. "Although vaccines and some antiviral drugs are available, it is crucial to understand influenza virus-host interactions at a molecular level in order to identify host vulnerabilities targeted by flu viruses, which could lead to developing new therapeutic options," said Lynch, whose lab focuses on the specific mechanisms and patterns of alternative RNA splicing and how it relates to human disease,

The transcription of DNA into messenger RNA—the process of a single gene encoding a single —isn't as straightforward as once thought. The phenomenon of alternative RNA splicing—where a single gene can encode multiple proteins—was discovered over 30 years ago in viruses.

The flu A genome is comprised of eight single-strand segments of RNA. Three of these segments use alternative splicing to produce two essential viral proteins each, which are important in helping the virus gain entry into host cells. Working with cultures of human lung cells, the team's proposed mechanism of how flu A virus interacts with human RNA splicing machinery suggests that keeping human splicing proteins from binding to the would help to stop its replication.

As a result, the researchers found that mutating sequences of the viral genome to prevent host proteins from binding caused viral RNA to splice incorrectly and eventually halt replication—thus slowing the spread of the virus in the body.

A balance between the two viral messenger RNAs must be maintained for the virus to successfully infect host cells and replicate. "Regulating splicing of the two viral proteins is a fundamental step in viral-host interaction and so a potentially new anti-viral remedy," Lynch said.

For now, her team is refining their understanding of the intricacies of viral reproduction in host cells. Their hope is to one day identify a specific molecular target for antiviral medications that can be used in the clinic.

Explore further: Researchers capture first representative of most abundant giant viruses in the sea

More information: Matthew G. Thompson et al, Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing, Nature Communications (2018). DOI: 10.1038/s41467-018-04779-4

Related Stories

Researchers capture first representative of most abundant giant viruses in the sea

March 29, 2018
Bodo saltans virus, the first isolated representative of the most abundant giant viruses in the sea, has been unveiled by researchers at the University of British Columbia.

Scientists established a comprehensive protein interactions map of the replication machinery of a chronic virus

December 20, 2017
Chronic viral infections like HIV or hepatitis are among the biggest threats to human health worldwide. While an acute viral infection usually results in full recovery and effective immune memory, chronic viruses evade the ...

Human genomic pathways to bronchitis virus therapy

November 18, 2015
Viral replication and spread throughout a host organism employs many proteins, but the process is not very well understood. Scientists at A*STAR have led a collaborative study to learn which host factors play a key role in ...

New insight about how viruses use host proteins to their advantage

April 2, 2018
Viruses have a very limited set of genes and therefore must use the cellular machineries of their hosts for most parts of their growth. A new study, led by scientists at Uppsala University, has discovered a specific host ...

Researchers discover possible new target to attack flu virus

April 10, 2014
(Medical Xpress)—Scientists at The University of Texas at Austin have discovered that a protein produced by the influenza A virus helps it outwit one of our body's natural defense mechanisms. That makes the protein a potentially ...

Against the clock—uncovering the first 30 minutes of viral infection

March 29, 2018
Researchers are unraveling the crucial first 30 minutes of viral invasion into a human cell.

Recommended for you

Researchers find infectious prions throughout eyes of patients with deadly sporadic Creutzfeldt-Jakob disease

November 20, 2018
By the time symptoms of sporadic Creutzfeldt-Jakob disease (sCJD) are typically discovered, death is looming and inevitable. But, in a new study, researchers at University of California San Diego School of Medicine with colleagues ...

Researchers a step closer to understanding how deadly bird flu virus takes hold in humans

November 19, 2018
New research has taken a step towards understanding how highly pathogenic influenza viruses such as deadly bird flu infect humans.

Infants born to obese mothers risk developing liver disease, obesity

November 16, 2018
Infant gut microbes altered by their mother's obesity can cause inflammation and other major changes within the baby, increasing the risk of obesity and non-alcoholic fatty liver disease later in life, according to researchers ...

New study shows NKT cell subsets play a large role in the advancement of NAFLD

November 16, 2018
Since 2015 it has been known that the gut microbiota could have a direct impact on nonalcoholic fatty liver disease (NAFLD), which affects up to 12% of adults and is a leading cause of chronic liver disease. In the November ...

Antibiotic prescribing influenced by team dynamics within hospitals

November 15, 2018
Antibiotic prescribing by doctors is influenced by team dynamics and cultures within hospitals.

Discovery suggests new route to fight infection, disease

November 14, 2018
New research reveals how a single protein interferes with the immune system when exposed to the bacterium that causes Legionnaires' disease, findings that could have broad implications for development of medicines to fight ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

rrwillsj
1 / 5 (2) Jun 23, 2018
A_B, pity that you didn't get treated for that syphilis that is causing you so much brain damage!

What? You spent your condom allowance on beer? You are a walking testimonial to bad decision making. With pitiful lack of self-discipline and having not a lick of common sense!

I hope all the girls and boys you infected have been treated? At your expense!

Have you no conscious?

Are you even capable of shame?

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.