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Zika virus likely circulated in Americas long before its detection

The Zika virus circulated in many regions of the Americas for several months before cases of infection were detected, according to new data from an international research team from the Broad Institute of MIT and Harvard and several collaborating institutions.

These findings, revealed today in Nature in a paper led by Pardis Sabeti of the Broad Institute and Harvard University, arise from an analysis of 174 Zika virus genomes — including the largest collection of new Zika virus genomes to date — sequenced from patient and mosquito samples collected in 11 affected countries and territories.

The paper’s co-authors include Hayden Metsky, a graduate student in the Sabeti lab, MIT’s Department of Electrical Engineering, and the Computer Science and Artificial Intelligence Laboratory, who is one of the paper’s first authors; Lee Gehrke, the Hermann L.F. von Helmholtz Professor in MIT’s Institute for Medical Engineering and Science (IMES); and Irene Bosch, a research scientist at IMES.

The genomic data allowed the research team to reconstruct for the first time the spread of the virus across South and Central America, the Caribbean, and into the southern United States.

In many of these regions, the virus circulated for months before local cases of infection were detected. Sabeti and colleagues’ analysis suggested that Zika was circulating in Brazil around February 2014, a year before that nation’s first confirmed infections were reported. Similarly, the virus appears to have arrived in Colombia, Honduras, Puerto Rico, and elsewhere in the Caribbean from 4.5 to 9 months before the first confirmed local infections, highlighting the importance of having sensitive and specific diagnostic tools early in an outbreak.

These results appear only now, months after the peak of the outbreak, because sequencing Zika virus has proved to be challenging, particularly when done directly from patient samples. The difficulty arises because Zika virus is typically present at very low levels in patients and disappears quickly. As a result, very few Zika genomes had been generated prior to this study, leaving researchers with little basis for understanding how the virus is spreading and evolving.

To address this lack of data, the team developed new laboratory and analytical methods for capturing robust Zika genomic data, and applied them to samples collected in partnership with collaborators in Brazil, Colombia, the Dominican Republic, Honduras, Jamaica, Puerto Rico, Massachusetts, and Florida to generate 110 new genomes for this study. The team combined those genomes with an additional 64 available in GenBank and in one of the study’s two companion papers, to carry out their analysis.

“We knew it was important to understand the viral populations driving the epidemic, which motivated us to tackle the challenges of sequencing Zika,” says Metsky. “Because the data we generated capture the geographic diversity of the virus across the Americas, they provide an opportunity to trace how and when the virus spread. Our data and findings will also support development of more effective molecular diagnostic tests, as well as improved public health surveillance tools.”

The work also highlights the importance of quickly creating trusted partnerships between researchers and across institutions and regions, and of sharing data openly during outbreaks.

“This collaboration has been about each partner sharing their unique resources and expertise — samples, protocols, analyses, insights — to help understand and fight Zika,” says Thiago Moreno L. Souza, a study co-senior author and senior research scientist at Fundação Oswaldo Cruz in Rio de Janiero, Brazil. “Sharing the data widely for the same end goal was an obvious extension of that ethos.”

The study was published together with two companion papers, one by Kristian Andersen from the Scripps Research Institute and colleagues examining Zika’s introduction into Florida, and the other by Oliver Pybus at Oxford University and colleagues examining the virus’s establishment and early spread within and beyond northeastern Brazil. All three teams committed to sharing data and ideas freely amongst themselves and to releasing their findings cooperatively and quickly.

“Collectively our goal was to capture as complete a picture of the genetic underpinnings of the epidemic in the Americas as we could. Working together was critical to reaching that goal,” says study co-senior author Bronwyn MacInnis, associate director of malaria and viral genomics in the Broad’s Infectious Disease and Microbiome Program. “Instead of competing for publication, we wanted our papers to leverage each other and reflect our commitment to the greater good.”

Zika remains a significant public health threat in affected countries and regions, highlighting the need for continued surveillance and research on the virus. According to MacInnis, the epidemic holds lessons about the role genomics can play in identifying and tracking emerging outbreaks early, before widespread infection occurs.

“Genomics allowed us to reconstruct how the virus traveled and changed across the epidemic — which also means that genomics could have helped detect it much earlier,” she says. “We were way behind the curve on Zika. We need to be well ahead of the next emerging viral threat, and genomics can have a role in achieving this.”

Support for this study was provided by Marc and Lynne Benioff, the National Institute of Allergy and Infectious Diseases, and other sources. Pardis Sabeti is an Investigator with the Howard Hughes Medical Institute.

The work was and continues to be part of a collaboration across nations. Those currently involved include the following investigators, together with their teams and collaborators: Thiago Moreno L. Souza, Patrícia T. Bozza, Wim Degrave, et al. at Oswaldo Cruz Foundation in Brazil; Fernando Bozza at Oswaldo Cruz Foundation and D’or Institute in Brazil; Salim Mattar at the University of Córdoba in Colombia; Luis A. Villar Centeno at the Industrial University of Santander in Colombia; Ivette Lorenzana at the National Autonomous University of Honduras in Honduras; Joshua Anzinger at The University of the West Indies in Jamaica; Andrew Rambaut at the University of Edinburgh in the UK; Sharon Isern and Scott F. Michael at Florida Gulf Coast University; Sandra Smole at the Massachusetts Department of Health; Irene Bosch and Lee Gehrke at MIT; and Kristian Andersen at The Scripps Research Institute.

Researchers engineer shape-shifting noodles

“Don’t play with your food” is a saying that MIT researchers are taking with a grain or two of salt. The team is finding ways to make the dining experience interactive and fun, with food that can transform its shape when water is added.

The researchers, from MIT’s Tangible Media Group, have concocted something akin to edible origami, in the form of flat sheets of gelatin and starch that, when submerged in water, instantly sprout into three-dimensional structures, including common pasta shapes such as macaroni and rotini.

The edible films can also be engineered to fold into the shape of a flower as well as other unconventional configurations. Playing with the films’ culinary potential, the researchers created flat discs that wrap around beads of caviar, similar to cannoli, as well as spaghetti that spontaneously divides into smaller noodles when dunked in hot broth.

The researchers presented their work in a paper this month at the Association for Computing Machinery’s 2017 Computer-Human Interaction Conference on Human Factors in Computing Systems. They describe their shape-morphing creations as not only culinary performance art, but also a practical way to reduce food-shipping costs. For instance, the edible films could be stacked together and shipped to consumers, then morph into their final shape later, when immersed in water.

“We did some simple calculations, such as for macaroni pasta, and even if you pack it perfectly, you still will end up with 67 percent of the volume as air,” says Wen Wang, a co-author on the paper and a former graduate student and research scientist in MIT’s Media Lab. “We thought maybe in the future our shape-changing food could be packed flat and save space.”

Wang’s co-authors are Lining Yao, lead author and former graduate student; Chin-Yi Cheng, a former graduate student; Daniel Levine, a current graduate student; Teng Zhang of Syracuse University; and Hiroshi Ishii, the Jerome B. Wiesner Professor in media arts and sciences.

“This project is the one of the latest to materialize our vision of ‘radical atoms’ — combining human interactions with dynamic physical materials, which are transformable, conformable, and informable,” Ishii says.

Programmable pasta

At MIT, Wang and Yao had been investigating the response of various materials to moisture. They were working mostly with a certain bacterium that can transform its shape, shrinking and expanding in response to humidity. Coincidentally, that same bacterium is used to ferment soybeans to make a common Japanese dish known as natto. Yao and Wang wondered whether other edible materials could be designed to change their shape when exposed to water.

They started playing around with gelatin, a substance that naturally expands when it absorbs water. Gelatin can expand to varying degrees depending on its density — a characteristic that the team exploited in creating their shape-transforming structures.

Yao and Wang engineered a flat, two-layer film made from gelatin of two different densities. The top layer is more densely packed, and thus able to absorb more water, than the bottom. When the entire structure is immersed in water, the top layer curls over the bottom layer, forming a slowly rising arch.

The researchers looked for ways to control where and to what degree the structure bends, so that they might create different three-dimensional shapes from the gelatin sheet. They eventually settled on 3-D printing strips of edible cellulose over the top gelatin layer. The cellulose strips naturally absorb very little water, and they found that the strips could act as a water barrier, controlling the amount of water that the top gelatin layer is exposed to. By printing cellulose in various patterns onto gelatin, they could predictably control the structure’s response to water and the shapes that it ultimately assumed.

“This way you can have programmability,” Yao says. “You ultimately start to control the degree of bending and the total geometry of the structure.”

Designing for a noodle democracy

Wang and Yao created a number of different shapes from the gelatin films, from macaroni- and rigatoni-like configurations, to shapes that resembled flowers and horse saddles.

Curious as to how their designs might be implemented in a professional kitchen, the team showed their engineered edibles to the head chef of a high-end Boston restaurant. The scientists and chef struck up a short collaboration, during which they designed two culinary creations: transparent discs of gelatin flavored with plankton and squid ink, that instantly wrap around small beads of caviar; and long fettuccini-like strips, made from two gelatins that melt at different temperatures, causing the noodles to sponataneously divide when hot broth melts away certain sections.

“They had great texture and tasted pretty good,” Yao says.

The team recorded the cellulose patterns and the dimensions of all of the structures they were able to produce, and also tested mechanical properties such as toughness, organizing all this data into a database. Co-authors Zhang and Cheng then built computional models of the material’s transformations, which they used to design an online interface for users to design their own edible, shape-transforming structures.

“We did many lab tests and collected a database, within which you can pick different shapes, with fabrication instructions,” Wang says. “Reversibly, you can also select a basic pattern from the database and adjust the distribution or thickness, and can see how the final transformation will look.”

The researchers used a laboratory 3-D printer to pattern cellulose onto films of gelatin, but they have outlined ways in which users can reproduce similar effects with more common techniques, such as screenprinting.

“We envision that the online software can provide design instructions, and a startup company can ship the materials to your home,” Yao says. “With this tool, we want to democratize the design of noodles.”

This research was funded, in part, by the MIT Media Lab and Food + Future, a startup accelerator sponsored by Target Corporation based in Cambridge, Massachusetts.