Broad Institute of MIT and Harvard, CCS
The zika virus was already circulating in Brazil in the first quarter of 2014, more than one year before infection cases were detected in the country, according to new data from an international study, revealed in Nature, conducted by Fiocruz researchers in partnership with the Broad Institute and institutions of several countries. The research also revealed that Brazil was the source of the outbreak in the Americas.
“Fiocruz and Broad originally worked to catalog the zika virus biodiversity in Brazil. Such work was expanded and became the largest study of zika virus genomics in the Americas, referring to the quantity of analyzed samples. As a result, we realized that the virus spread from Brazil to the Americas, leading to need for reinforcing the surveillance in all such countries”, explained the specialist from the Fiocruz Center for Health Technological Development (CDTS/Fiocruz) Thiago Souza, who took part in the study.
The study analyzed more than 200 samples of patients and infected mosquitoes, resulting in 110 zika virus genomes distributed in 11 affected countries. The analysis includes the largest collection of new zika virus genomes investigated until now. The genomic data enabled the team of researchers to rebuild the virus spreading in South America, Central America, the Caribbean, and the South of the United States for the first time.
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. Similarly to Brazil, 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 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,” said study co-first author Hayden Metsky, a graduate student in the Sabeti lab. “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.
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 the University of Oxford 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 release 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 ,” said 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 said. “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.
*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:
Pardis Sabeti, Howard Hughes Medical Institute.
Thiago Moreno L. Souza, Patrícia T. Bozza, Wim Degrave, et al., Oswaldo Cruz Foundation, Brazil
Fernando Bozza, Oswaldo Cruz Foundation and D’or Institute, Brazil
Salim Mattar, Universidad de Córdoba, Colombia
Luis A. Villar Centeno, Universidad Industrial de Santander, Colombia
Ivette Lorenzana, Universidad Nacional Autónoma de Honduras, Honduras
Joshua Anzinger, The University of the West Indies, Jamaica
Andrew Rambaut, University of Edinburgh, UK
Sharon Isern and Scott F. Michael, Florida Gulf Coast University, USA
Sandra Smole, Massachusetts Department of Health, USA
Irene Bosch and Lee Gehrke, Massachusetts Institute of Technology, USA
Kristian Andersen, The Scripps Research Institute, USA