Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.
The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT.
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; The Scripps Research Institute, Scripps Translational Science Institute, La Jolla, CA 92037, USA. Electronic address: andersen@scripps.edu.
Kristian G
KG
Andersen
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Biological Sciences, University of Montréal, Montréal, QC H2V 2S9, Canada.
B Jesse
BJ
Shapiro
Broad Institute, Cambridge, MA 02142, USA.
Christian B
CB
Matranga
Broad Institute, Cambridge, MA 02142, USA; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Rachel
R
Sealfon
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Aaron E
AE
Lin
Tulane Health Sciences Center, Tulane University, New Orleans, LA 70118, USA.
Lina M
LM
Moses
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; Department of Biological Sciences, College of Natural Sciences, Redeemer's University, Redemption City, Osun State, Nigeria.
Onikepe A
OA
Folarin
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Augustine
A
Goba
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
Ikponmwonsa
I
Odia
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
Philomena E
PE
Ehiane
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone; Eastern Polytechnic College, Kenema, Eastern Province, Sierra Leone.
Mambu
M
Momoh
Broad Institute, Cambridge, MA 02142, USA.
Eleina M
EM
England
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Sarah
S
Winnicki
Zalgen Labs, Germantown, MD 20876, USA.
Luis M
LM
Branco
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Stephen K
SK
Gire
Broad Institute, Cambridge, MA 02142, USA.
Eric
E
Phelan
Broad Institute, Cambridge, MA 02142, USA.
Ridhi
R
Tariyal
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Ryan
R
Tewhey
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
Omowunmi
O
Omoniwa
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone; Eastern Polytechnic College, Kenema, Eastern Province, Sierra Leone.
Mohammed
M
Fullah
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Richard
R
Fonnie
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Mbalu
M
Fonnie
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Lansana
L
Kanneh
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Simbirie
S
Jalloh
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Michael
M
Gbakie
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Sidiki
S
Saffa
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Kandeh
K
Karbo
Broad Institute, Cambridge, MA 02142, USA.
Adrianne D
AD
Gladden
Broad Institute, Cambridge, MA 02142, USA.
James
J
Qu
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Matthew
M
Stremlau
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Mahan
M
Nekoui
Broad Institute, Cambridge, MA 02142, USA.
Hilary K
HK
Finucane
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.
Shervin
S
Tabrizi
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Joseph J
JJ
Vitti
Broad Institute, Cambridge, MA 02142, USA.
Bruce
B
Birren
Broad Institute, Cambridge, MA 02142, USA.
Michael
M
Fitzgerald
Broad Institute, Cambridge, MA 02142, USA.
Caryn
C
McCowan
Broad Institute, Cambridge, MA 02142, USA.
Andrea
A
Ireland
Broad Institute, Cambridge, MA 02142, USA.
Aaron M
AM
Berlin
Broad Institute, Cambridge, MA 02142, USA.
James
J
Bochicchio
Broad Institute, Cambridge, MA 02142, USA.
Barbara
B
Tazon-Vega
Broad Institute, Cambridge, MA 02142, USA.
Niall J
NJ
Lennon
Broad Institute, Cambridge, MA 02142, USA.
Elizabeth M
EM
Ryan
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA.
Zach
Z
Bjornson
Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA 02115, USA.
Danny A
DA
Milner
Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA 02115, USA.
Amanda K
AK
Lukens
College of Medicine, Columbia University, New York, NY 10032, USA.
Nisha
N
Broodie
Zalgen Labs, Germantown, MD 20876, USA.
Megan
M
Rowland
Zalgen Labs, Germantown, MD 20876, USA.
Megan
M
Heinrich
Zalgen Labs, Germantown, MD 20876, USA.
Marjan
M
Akdag
Tulane Health Sciences Center, Tulane University, New Orleans, LA 70118, USA.
John S
JS
Schieffelin
Tulane Health Sciences Center, Tulane University, New Orleans, LA 70118, USA.
Danielle
D
Levy
Nigerian Federal Ministry of Health, Abuja, Federal Capital Territory, Nigeria.
Henry
H
Akpan
Tulane Health Sciences Center, Tulane University, New Orleans, LA 70118, USA.
Daniel G
DG
Bausch
The National Aeronautics and Space Administration, Johnson Space Center, Houston, TX 77058, USA.
Kathleen
K
Rubins
The University of Texas School of Public Health, Brownsville, TX 77030, USA.
Joseph B
JB
McCormick
Broad Institute, Cambridge, MA 02142, USA.
Eric S
ES
Lander
Department of Virology, Bernhard-Nocht-Institute for Tropical Medicine, 20259 Hamburg, Germany.
Stephan
S
Günther
NIAID Integrated Research Facility, Frederick, MD 21702, USA.
Lisa
L
Hensley
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
Sylvanus
S
Okogbenin
Broad Institute, Cambridge, MA 02142, USA.
Stephen F
SF
Schaffner
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
Peter O
PO
Okokhere
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
S Humarr
SH
Khan
Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Eastern Province, Sierra Leone.
Donald S
DS
Grant
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
George O
GO
Akpede
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
Danny A
DA
Asogun
Broad Institute, Cambridge, MA 02142, USA.
Andreas
A
Gnirke
Broad Institute, Cambridge, MA 02142, USA.
Joshua Z
JZ
Levin
Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; Department of Biological Sciences, College of Natural Sciences, Redeemer's University, Redemption City, Osun State, Nigeria. Electronic address: happic@run.edu.ng.
Christian T
CT
Happi
Tulane Health Sciences Center, Tulane University, New Orleans, LA 70118, USA.
Robert F
RF
Garry
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: psabeti@oeb.harvard.edu.
Pardis C
PC
Sabeti
D000354:Africa, Western / Q000453:epidemiology; D000818:Animals; D005075:Biological Evolution; D004197:Disease Reservoirs; D029043:Ebolavirus / Q000235:genetics; D014644:Genetic Variation; D016679:Genome, Viral; D006023:Glycoproteins / Q000235:genetics; D019142:Hemorrhagic Fever, Ebola / Q000821:virology; D006801:Humans; D007835:Lassa Fever / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D007836:Lassa virus / Q000145:classification / Q000235:genetics* / Q000502:physiology; D051189:Murinae / Q000235:genetics; D009154:Mutation; D009549:Nigeria / Q000453:epidemiology; D012367:RNA, Viral / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics; D015047:Zoonoses / Q000453:epidemiology / Q000821:virology
D006023:Glycoproteins; D012367:RNA, Viral; D014764:Viral Proteins