What causes a virus to suddenly begin infecting large numbers of people?
Scientists have long known that the process they call "viral emergence" involves a wide variety of factors. Some are changes in the environment, either generated by natural causes or human activity. Others are internal, arising from accidental changes — mutations —in the virus' genetic code.
Studying such mutations in different strains of the chikungunya virus has helped University of Texas Medical Branch researchers solve one of the most puzzling mysteries of chikungunya's emergence in Asia. They describe their results in an article in the online "Early Edition" section of the Proceedings of the National Academy of Sciences.
Chikungunya, which originated in Africa, is carried by mosquitoes and causes intensely painful arthritis that can last for months or years. Thanks to a discovery made at UTMB, scientists know that the virus' rapid spread was launched by a single mutation in an African strain of the virus.
The alteration was so small — a single amino acid change in one of the virus' exterior "envelope" proteins — that a researcher compared it to "a single missing comma in a six-page short story." But this so-called "E1-A226V mutation" made it possible for the virus to efficiently infect Aedes albopictus, a species of mosquito found nearly worldwide.
The mutated strain of the virus took full advantage of its new host, infecting millions of people as it spread across India, Thailand and Malaysia. It even jumped to northern Italy, carried by an infected traveler, where it established itself in the local Aedes albopictus mosquito population.
This albopictus-adapted strain's success raised a fundamental question, for this was not chikungunya's first visit to Asia. Strains of the virus transmitted by another mosquito species, Aedes aegypti, have caused sporadic outbreaks there for nearly six decades. If the virus was changing all the time, and only one minor mutation was necessary to switch the virus from aegytpi to albopictus — a more widespread vector — why hadn't that mutation happened in the strains that had arrived in Asia 60 years before?
"Asia is Aedes albopictus' native territory, but we can't find any evidence of chikungunya transmission by albopictus until the arrival of this new strain," said UTMB pathology professor Scott Weaver, senior author on the PNAS paper. "It was surprising to us that strains of this apparently very adaptable virus circulated in Asia for 60 years without making the adaptation that would allow them to be transmitted by albopictus."
To find out what was going on, Weaver and his colleagues — lead author and postdoctoral fellow Konstantin Tsetsarkin, postdoctoral fellow Rubing Chen, research technician Grace Leal, assistant professor Naomi Forrester, professor Stephen Higgs, and research associate Jing Huang — conducted experiments based on the hypothesis that some part of the Asian chikungunya strains' genetic code was suppressing the key mutation whenever it occurred and thus keeping it from infecting Aedes albopictus.
Using two different Asian strains into which they inserted the E1-A226V mutation, they systematically added additional genetic portions from the African strain, followed by specific mutations to determine which interacted with E1-A226V. Then they tested each change to see whether it affected Aedes albopictus infectivity.
Ultimately, they found that a single genetic element — which also changed an amino acid in the same envelope protein altered by the E1-A226V mutation — increased the Asian chikungunya strains' ability to infect Aedes albopictus by a hundredfold.
"This old Asian lineage needs an additional mutation to adapt to Aedes albopictus, and we think that's what protected India and Southeast Asia from much larger epidemics over the last 60 years," Weaver said. "But some African strains only needed one mutation to spark much larger outbreaks. And now, a strain that emerged from Africa in 2004 seems to be displacing the old Asian strains wherever it goes."
The chikungunya story, Weaver said, demonstrates how small genetic differences among viruses can have dramatic and unexpected effects on their ability to cause human disease. This study also will allow researchers to predict the amount of disease chikungunya may cause if it becomes endemic in the Americas.
"We don't really have the ability to predict when these viruses are going to suddenly mutate and change from one host to another. We can figure out how it happened retrospectively, but we have no idea how many near misses there are," Weaver said. "This was an opportunity to understand one situation where for a long time epidemic emergence didn't happen for a virus in Asia, and how it did happen suddenly when another strain got loose from Africa and started spreading around the globe."
ABOUT UTMB Health: Established in 1891, Texas' first academic health center comprises four health sciences schools, three institutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, and a health system offering a full range of primary and specialized medical services throughout Galveston County and the Texas Gulf Coast region. UTMB Health is a component of the University of Texas System and a member of the Texas Medical Center.The University of Texas Medical Branch at Galveston
Jim Kelly | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences