Nav: Home

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018

Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations in the genome of influenza A may help counteract the weakening effects of other mutations.

Influenza A causes tens of thousands of deaths in the U.S. every year, despite vaccination efforts. It persists, in large part, due to continual changes in the sequence of amino acid "building blocks" that make up the viral protein hemagglutinin, enabling it to avoid recognition and removal by immune system antibodies. Many of these mutations can reduce a virus's fitness--its ability to make more copies of itself--raising the question of how viruses compensate to recover their mojo.

Ivan Kosik of the National Institute of Allergy and Infectious Diseases, Maryland, and colleagues investigated hemagglutinin mutations to better understand the mechanisms by which influenza A viruses maintain fitness despite continual mutation. They focused on influenza A variants with mutations that enabled them to escape antibodies from mice, guinea pigs, or chickens.

To identify the accumulated mutations that restored viral fitness, the researchers sequenced the viral RNA using a supersensitive method called PrimerID sequencing, which enables tracking of all individual viral genomes so that any relevant mutations can be spotted. They found several mutations of particular interest that add a new sugar molecule to the hemagglutinin, thus creating a novel "N-linked glycan" site.

How does this help the virus to replicate? It turns out, that the new sugar allows the virus to regain "Goldilocks" binding to the host cell: not too weak, but not too tight either. In escaping the immune system, the new mutations can inadvertently disrupt this golden binding point, which can be remedied by adding a sugar molecules in the just the part of the hemagglutinin.

These findings improve understanding of the mechanisms that make flu outbreaks so difficult to prevent, and inform efforts to design more effective flu vaccines that are less easily thwarted by continual mutation. The results also demonstrate the value of PrimerID sequencing to provide a high-resolution view of all the mutations present in a given viral population--something that conventional deep sequencing approaches cannot do as accurately or efficiently. This level of understanding is necessary to keep up with the flu, which despite is miniscule size, has managed to outsmart humans trying to foil the havoc it wreak each flu season.
-end-
In your coverage please use this URL to provide access to the freely available article in PLOS Pathogens: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006796

Citation: Kosik I, Ince WL, Gentles LE, Oler AJ, Kosikova M, Angel M, et al. (2018) Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs. PLoS Pathog 14(1): e1006796. https://doi.org/10.1371/journal.ppat.1006796

Funding: All work funded directly by US gov?t. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

PLOS

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".