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LASSA FEVER: RUN SCIENTISTS, OTHERS UNCOVER ORIGINS, EVOLUTION OF VIRUS
News > Postgraduate Study      |      Posted: August 24, 2015 17:25:45pm GMT |      Views: 3752
The Director,African Centre of Excellence For Genomics of Infectious Diseases(ACEGID),Professor Christian Happi(right) discussing with the Vice-Chancellor,Professor Debo Adeyewa during the visit of the US Public Broadcasting Service to the university.
The Director,African Centre of Excellence For Genomics of Infectious Diseases(ACEGID),Professor Christian Happi(right) discussing with the Vice-Chancellor,Professor Debo Adeyewa during the visit of the US Public Broadcasting Service to the university.

Pioneer dean of the Postgraduate College of the Redeemer’s University, Ede, Osun State and foremost professor of Molecular Biology and Genomics, Christian Happi and Dr. Onikepe Folarin also of the same institution, alongside others, recently published new findings showing the ancient roots of the deadly Lassa virus.

This was revealed in the latest issue of the prestigious scientific journal Cell published on Thursday August 13, 2015.

In the new study, Professor Happi 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.

Happi is the Director of the World Bank funded African Center of Excellence for Genomics of infectious Diseases (ACEGID) at Redeemer’s University.

According to Happi,“This is the largest catalog of Lassa fever virus sequences ever generated in the world, and in the history of virology and genomics.”

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.

He added that “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.  These findings also support our previous demonstration that the Yoruba race of Nigeria has been under natural selection to evolve resistance to the virus.

“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,” he said.

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.

For Pardis Sabeti, “Lassa and Ebola are not only potential global threats, but have likely been circulating in communities for many years. 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.

Reacting to the publication Vice-Chancellor of the Redeemer’s University, 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.”

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.”

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 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.

Other institutions that contributed to the research are Harvard University, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, 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.

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