Influenza Virus Can Overcome Potentially Crippling Mutations New research could improve the effectiveness of flu vaccines and therapies
June 14, 2017
Scientists at The Scripps Research Institute (TSRI) have shown that for the virus that causes the flu, two wrongs can sometimes make a right.
In a new study, the researchers demonstrated that in rare instances, influenza viruses handicapped by a single mutation can overcome their disadvantage with the aid of other mutations a phenomenon known as epistasis.
The term epistasis means that the combined effect of two individual mutations can't be predicted ahead of time, said TSRI Postdoctoral Researcher and study first author Nicholas Wu. Individually, each of these mutations kill the virus, but together, they compensate for each other's harmful effects.
The unexpected finding, published today in the journal Cell Host & Microbe, could have implications for the development of flu vaccines and drug therapies. This study shows that the evolution of the influenza virus can surprise us, Wu said, but if we know ahead of time what kind of mutations can be accommodated at a particular site on the virus, we'll have a better idea of how to develop drugs or antibodies to target that site.
It has long been a dream to learn where influenza can go, rather than where it has been, said Richard Lerner, Lita Annenberg Hazen Professor of Immunochemistry at TSRI. Lerner co-led the new study with Ian Wilson, Hansen Professor of Structural Biology and chairman of the Department of Integrative Structural and Computational Biology at TSRI.
In the new study, Wu and his colleagues set out to investigate which mutations influenza virus could tolerate. They used genetic engineering techniques to introduce random mutations to the receptor binding site (RBS) of hemagglutinin, a spiky, mushroom-shaped protein displayed on the surface of the influenza virus. Hemagglutinin allows the virus to stick to and fuse with the membranes of host cells, and RBS plays a critical role in mediating the first step of this binding process.
The team introduced different combinations of single, double and even triple mutations to the RBS site of influenza H1N1 and H3N2 strains and then let the viruses replicate. Next, they used a technique called next-generation sequencing to conduct a quick census of the different mutations present in their virus population.
In order to characterize the viability or fitness effect of different individual mutations and combinations of mutations, the TSRI scientists infected mammalian cell cultures with the mutant viruses. Those viruses that can't infect the cells die, and the ones that can survive keep replicating, Wu said.
After 24 hours, the team performed a second round of next-generation sequencing to characterize the mutations of the surviving viruses. As expected, the vast majority (96 percent) of RBS single mutations proved lethal to the virus, but a remarkably large number of mutations (about 20 percent) were beneficial to the viruses when combined with other mutations.
We were surprised at how many combinations of two and three mutations were permissive for retention of the key functional activity of receptor binding, said Wilson. Many of the mutation combinations the team observed have not been seen in nature before, he added, and if not taken into consideration could allow influenza viruses to escape antibodies that target the RBS site.
Most of the viable mutation combinations the team uncovered occurred on a specific part of the RBS known as the 220-loop. Scientists have long known that an epistatic effect in this region was responsible for allowing avian flu strains to make the jump to humans in the past, but the discovery of other viable mutation combinations suggests there is much greater functional DNA sequence diversity in the 220-loop than previously thought.
A better understanding of which mutation combinations are permissible and which are not could help researchers narrow down the spectrum of mutations that should be targeted with antibodies and antiviral molecules, the scientists say. It also suggests that perhaps we should avoid trying to target regions such as the 220-loop, which appear to be relatively tolerant of mutations, Wu said.
Epistasis likely is not unique to influenza virus, Wilson said. We have not looked yet experimentally for epistasis in other viruses, he added, but it may indeed be worthwhile to consider whether it is present in other systems.
The article, Diversity of functionally permissive sequences in the receptor-binding site of influenza hemagglutinin, also included study co-authors Jia Xie, Tianqing Zheng, Corwin M. Nycholat, Geramie Grande and James C. Paulson of TSRI.
This work was supported by funds from the National Institutes of Health (grants R56 AI117675 and R01 AI114730) and the Croucher Foundation.
Infectious Diseases Immunology & Microbiology Integrative Structural & Computational Biology Lerner, Richard Wilson, Ian
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
13/05/2026
New Adobe Premiere Color Grading Mode Accelerated on NVIDIA GPUs
Joel Pennington May 13, 2026
0 Comments
New NVIDIA RTX-accelerated features streamlin...
13/05/2026
Grass Valley announced that dB Broadcast has delivered new IP-based outside broadcast (OB) trucks for Cloudbass, featuring Grass Valley LDX 100 Series cameras a...
13/05/2026
Ikegami will exhibit the latest additions to its wide range of broadcast production cameras, control units, viewfinders and monitors on stand 5D3-1 at Broadcast...
13/05/2026
FISE, working with the founding members of the XR Sports Alliance (XRSA), Accedo, Qualcomm Technologies, Inc. and HBS, have collaborated to develop an immersive...
13/05/2026
Canon Unveils New EOS R6 V Full-Frame EOS Camera and RF20-50mm F4 L IS USM PZ Bu...
13/05/2026
Boston Conservatory at Berklee Honors Beth Morrison and Moses Pendleton at Comme...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Creative software developer Foundry today announced the latest developments on Nuke Stage. A purpose-built application for end-to-end virtual production and in-...
13/05/2026
A definitive portrait of one of Ireland's most influential musicians
New TV documentary airs Monday 18 May on RT One and RT Player at 9.35pm
Watch the...
13/05/2026
Agentic AI is changing the way users get work done. Following the success of OpenClaw, the community is embracing new open source agentic frameworks. The latest...
13/05/2026
Reinforcement-learning agents - AI systems that learn by trial and error - can c...
12/05/2026
Beyond the Hype: A Strategic Post-Hoc Analysis of NAB 2026 If NAB Show 2026 had an underlying theme, it was a quiet, industry-wide pivot from the high-energy sp...
12/05/2026
Guntermann and Drunck (G&D), a Panoptec Technologies Group company, and CT Square, led by Chandresh Shah, have announced a joint venture to distribute G&D and V...
12/05/2026
With 30 days until the start of the FIFA World Cup 2026, Telemundo, the exclusive Spanish-language home of the tournament in the United States, has announced th...
12/05/2026
The NHL has announced the return of Stanley Pup for its third consecutive year, a 90-minute special featuring adoptable rescue dogs competing on a miniature rin...
12/05/2026
NBCUniversal presented its 2026 Upfront to advertisers at Radio City Music Hall, detailing upcoming programming across NBC, Peacock, Bravo, and Versant properti...
12/05/2026
FOX Sports has announced funding for the Fandom and Social Connection Initiative at Harvard Kennedy School's Shorenstein Center on Media, Politics, and Publ...
12/05/2026
TNDV and Live Media, both divisions of Live Media Group, supported live broadcast coverage around NCAA Final Four weekend in Indianapolis, including the March M...
12/05/2026
The European Football Alliance (EFA) has announced a content distribution agreement with Fubo Sports Network, the free ad-supported streaming TV (FAST) channel ...
12/05/2026
For the first time, Spanish-speaking fans in the U.S. will have two separate tel...
12/05/2026
CP Communications led a comprehensive spectrum management initiative on behalf of Churchill Downs during Kentucky Derby week, coordinating RF assets across the ...
12/05/2026
LiveU has announced a strategic partnership with DRONERESPONDERS, a 501(c)3 non-...
12/05/2026
Open Broadcast Systems has announced that BMC TV, a specialist in IP transport of broadcast content, has selected the Open Broadcast Systems 5G Flyaway solution...
12/05/2026
NEP Europe, part of NEP Group, has announced it will deliver broadcast solutions...
12/05/2026
Grass Valley has announced continued collaboration with Ravensbourne University ...
12/05/2026
Stats Perform has announced the launch of Opta Pulse, an AI-assisted video creation and distribution platform for leagues, rights holders, and broadcasters. The...
12/05/2026
FOX Sports has announced a collaboration with Sesame Workshop to integrate Sesame Street characters into FOX Sports' FIFA World Cup 2026 programming. Conten...
12/05/2026
To date, NHL Productions has produced 19 broadcasts with commentary in American Sign Language
NHL in ASL (American Sign Language) may be just one show, but the...
12/05/2026
Google's Brian Albert: creators, athletes, highlights, nostalgia, second-scr...
12/05/2026
A still from Past Lives by Celine Song, an official selection of the Premieres program at the 2023 Sundance Film Festival. (Courtesy of Sundance Institute | p...
12/05/2026
Spotify is where fans and artists come together, turning discovery into somethin...
12/05/2026
Features patented Marco-MMC clocking technology
Black Lion Audio's latest release combines the company's expertise in clocking with their renowned p...
12/05/2026
New Track Panel, sequencer upgrades & more
Following their recent public beta release, Reason Studios have announced the full release of Reason 14. With the...
12/05/2026
One month to go! SBS reveals expansive FIFA World Cup 2026 lineup beyond the pi...
12/05/2026
Rohde & Schwarz presents its advanced solutions for power electronics testing at...
12/05/2026
aconnic AG (ISIN: DE000A0LBKW6), Munich, has developed a modified fund raising p...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
Tyrell Corporation, specialists in high-end live sports and entertainment broadcasts, was tasked with delivering compelling broadcast coverage of premier equest...
12/05/2026
Registration is now open for IBC2026 as the global media, entertainment and technology community prepares to converge on the RAI Amsterdam from 11 14 September ...
12/05/2026
Ross Video, a global leader in live video production technology, will present its latest innovations and integrated production workflows at BroadcastAsia 2026, ...
12/05/2026
500 selected leaders from around the world across start-ups, corporates, and venture capital. Over 50bn in assets under management among attending investors, a...
Influenza Virus Can Overcome Potentially Crippling Mutations New research could improve the effectiveness of flu vaccines and therapies
