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ACEGID, Redeemer’s University Scientists Discover the Ancient Origins of Deadly Lassa Fever Virus.
News > Update      |      Posted: August 27, 2015 10:07:12am GMT
Professor Christian Happi, Centre Director for Africa Centre of Excellence for Genomic of Infectious Diseases (ACEGID) and also the Dean of the College of Postgraduate Studies, Redeemer's University

Ede, Osun State, Nigeria—August 13, 2015—Leading an international team of Scientists in Nigeria, West Africa and North America, Professor Christian Happi of the Department of Biological Sciences and Director of the World Bank funded African Center of Excellence for Genomics of infectious Diseases (ACEGID) at Redeemer’s University, Ede, Osun State, Nigeria, has published new findings showing the ancient roots of the deadly Lassa virus, a relative of Ebola virus, and how Lassa virus has changed over time.   The new study “Clinical sequencing uncovers origins and evolution of Lassa virus” was published on Thursday August 13, 2015 in the prestigious scientific Journal Cell.

 

In the new study, Professor Happi’s led team—which included Professors Pardis Sabeti and Joshua Levin of Harvard University and the Broad Institute, Robert F. Garry of Tulane University, as senior authors—used a technique called next-generation sequencing to sequence and analyze the genomes of 196 Lassa virus samples taken from human patients and wild Mastomys natalensis (rats) in Nigeria and Sierra Leone.  They used Illumina sequencing to assemble 183 LASV genomes from clinical samples collected in Sierra Leone and Nigeria, together with 2 LASV genomes from laboratory isolates and 11 LASV genomes from field samples of its rodent reservoir, Mastomys natalensis. “This is the largest catalog of Lassa fever virus sequences ever generated in the world, and in the history of virology and genomics.” said Professor Christian Happi, a senior and corresponding authors of the publication.

 

The genomic and molecular clocking data showed that Lassa virus originated from present day Nigeria about 1,060 years ago.   This surprised the team of researchers, as Lassa fever was first described in Nigeria in 1969. “Although we were surprised, the data has led us to the discovery that Lassa fever virus is a very ancient virus with roots in Nigeria” said Happi.  “These findings also support our previous demonstration that the Yoruba race of Nigeria has been under natural selection to evolve resistance to the virus” added the professor of molecular biology and genomics, Christian Happi.

 

The researchers found that the virus spread out of Nigeria about 400 years ago and over the past couple of hundred years moved into Guinea (220 years ago), Liberia (180 years ago) and Sierra Leone (150 years ago)—the same part of the world where the largest outbreak of Ebola virus has been raging since 2013. As Lassa virus spread, the virus mutated and seemed to better adapt to mammalian hosts.

 

“This ground breaking research has now given us and the scientific community a better insight into how the Lassa virus is evolving.  The findings are certainly very critical for development of new therapies and vaccines against Lassa fever” said Professor Happi.

 

 

Like Ebola, Lassa is a fatal, hemorrhagic fever virus. It kills more than 5,000 people each year, most of whom live in Sierra Leone, Nigeria, Liberia, and Guinea. Despite its impact, little research had been done on the virus until 2009. The same was true of Ebola before the recent outbreak. “Lassa and Ebola are not only potential global threats, but have likely been circulating in communities for many years,” said Pardis Sabeti. “It is a greatly overlooked public health challenge but also an opportunity to set up capacity to diagnose, treat and research these viruses now, before the next major outbreak.”

 

 

The new data also show that most Lassa fever cases are caused by frequent “spillover” infections from the wild rodent reservoir to humans, rather than spreading from human to human. “The reason Lassa hasn’t yet grown into this huge epidemic is because there is limited transmission between humans and that’s a major difference between Lassa virus and Ebola virus.” Said Kristian Andersen, an assistant professor at the Scripps Research Institute in La Jolla, California, and one of three co-first authors of the Cell paper.

 

The team also examined the diversity of Lassa fever viral species infecting humans, and rodents and found much more diversity among the latter. Because the rodents can be infected without becoming ill or dying, they are considered chronic carriers in whom there is more opportunity for the virus to mutate and evolve.

Surprisingly, the researchers also saw a few human samples containing more diverse viral strains than normal, suggesting that some people might be infected for longer than previously thought.  “If this is the case, it means that the virus may be present as a chronic, symptom-free infection in many people than are typically diagnosed” argued Happi.  He further stated that the consortium is currently using the genomics for next generation sequencing platform available at ACEGID, Redeemer’s University to sequence blood samples from healthy individuals across West Africa to determine whether the virus is present.

 

The diversity findings may also point to an immune escape mechanism wherein the virus develops mutations that allow it to evade an infected host’s immune response. “We found that, of the within-host mutations that affect protein structure, a surprisingly high number fall in parts of a Lassa surface protein targeted by the human immune system,” said Jesse Shapiro, a co-first author based at the University of Montreal. “This could have implications for vaccine design because it might mean that the virus is able to evade vaccine-induced immunity.” But the team also found that these particular mutations are rarely passed from one host to another, suggesting that, while they do provide adaptive immune escape within the host, “they may be evolutionary dead-ends that are unfit to transmit,” Shapiro said. The team is now undertaking further research to follow up on the immune escape hypothesis.

 

This publication is the outcome of a huge international collaborative effort led by researchers at Redeemer’s University, Ede, and Irrua specialist Teaching Hospital, Edo State, Nigeria, The Nigerian Federal Ministry of Health, and involving researchers from 16 other different institutions in West Africa and the United States of America. "It took us many years to form this consortium, set up the infrastructure, develop the sequencing protocols that enabled all these discoveries” said Dr. Onikepe Folarin, a lead author in the paper and a senior Lecturer in the Department of Biological Sciences as well as a principal investigator at ACEGID, Redeemer’s University.

 

Reacting to the publication of the discovery of the origin of the Lassa fever virus by the research team led by Redeemer’s University Scientists, the Vice-Chancellor of the institution, Professor Z. Debo Adeyewa said “ These major discoveries go to say that Nigerian and African researchers can use cutting-edge technologies to lead formidable research that can result in development of new drugs and vaccines against dreadful diseases like Lassa fever and Ebola Virus Disease.” “The critical role that Redeemer’s University played in diagnosis and containment of Ebola Virus Disease in Nigeria in addition to this ground breaking research has placed the University among the leading research institutions in Africa and the World” Professor Adeyewa further stated.

 

Also reacting to the groundbreaking research work, the former Vice-Chancellor of Redeemer’s University Professor Oyewale Tomori, a World renowned virologist and President of the Nigerian Academy of Sciences said the publication was” a great paper of significant historical and epidemiological value”

 

Overall, these findings from this new study cast LASV as a virus that has a fundamentally different evolutionary and transmission history to EBOV: owing to more ancient origins, LASV is more genetically diverse and better adapted to human hosts. “Lassa fever is probably less transmissible than Ebola—either from rodent to human, or from human to human,” Andersen explained. “Since many rodents (Mastomys natalensis) are infected and live in households in West Africa, there may be more 'opportunities' for transmission from rodent to human to occur.” said Happi.  This means that strategies for containing Lassa could be fundamentally different from those used to contain Ebola and would focus more on the rodent reservoir population rather than minimizing human-to-human contact.

 

While the discoveries in this research work are exciting from a scientific perspective, Professor Happi is still reminded by the fact that, “Our people are dying every day of Lassa fever, Ebola virus disease and other infectious diseases.  However, we will continue this type of work till we find and/or enable the cures and vaccines against Lassa fever and other infectious diseases that burden Africa”

 

 

 

Other institutions that contributed to the research:

Harvard University, Massachusetts Institute of Technology (MIT), Irrua Specialist Teaching Hospital, Zalgen Labs, Stanford University, Harvard School of Public Health, Columbia University, Nigeria Federal Ministry of Health, National Aeronautics and Space Administration (NASA), University of Texas School of Public Health, Bernhard-Nocht-Institute for Tropical Medicine, Viral Hemorrhagic Fever Consortium and the National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility.

 

About Redeemer’s University and the African Center of Excellence for Genomics of Infectious Diseases (ACEGID).

 

Redeemer’s University (RUN) is one of the fastest growing faith-based not-for-profit University in Africa, focusing on education and research, especially in the biomedical sciences. RUN is internationally recognized through ACEGID for its contributions to science and health, including its role in using molecular biology and genomics in providing insight into infectious diseases biology and laying the foundation for new treatments and vaccines.  The World Bank established ACEGID, with support from a NIH funded project (H3Africa consortium). ACEGID is using the genomics platform that it has established to train a critical mass of well trained African scientists in the field of genomics of infectious diseases where its renowned scientists not only helped diagnosed and contained Ebola virus disease in Nigeria, but have made major discoveries that have significantly impacted health development in Africa.  The RUN-ACEGID graduate program, which awards PhD degrees in molecular biology and genomics, Bioinformatics, microbiology, biochemistry, chemistry and mathematics with bias in infectious diseases is the best of 21 African Centers of Excellences supported by the World bank in Africa.

For more information, see:

www.run.edu.ng

www.acegid.org

 

 

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