Almost all MSI1 protein in the developing embryo is produced in the neural stem cells that will eventually develop into the baby’s brain, which could explain why these cells are so vulnerable to Zika.
Since 2016 thousands of children across South America have been born with microcephaly, which causes abnormally small heads, after their mothers became infected with the Zika virus during pregnancy.
The overlap between Zika cases in pregnant women and an increase in babies born with microcephaly strongly suggested that the virus targets stem cells in the developing human brain, but why and how has remained a mystery. This study is the first to associate MSI1 with microcephaly and the Zika virus.
Professor Bayliss said: “Zika shocked the world when it flared up and affected the lives of so many children and their families. Through dedicated research work we believe we have taken a step forward in understanding how it operates, and by doing so scientists can begin to think about how to disrupt it at a molecular level.”
Dr Fanni Gergely from the University of Cambridge, who led the research project, said: “The development of a healthy human brain is an incredibly complex process that relies on stem cells and the coordinated actions of many genes.
“We’ve shown for the first time this interaction between Zika and MSI1 – with MSI1 getting exploited by the virus for its own destructive life cycle, turning MSI1 into the enemy within. We hope that in the future this discovery could lead to ways of generating potential Zika virus vaccines.”
The researchers found when the Zika virus enters these stem cells, it hijacks MSI1 for its own replication and damagesthe cells in at least two ways.
In both of these scenarios neural stem cells, crucial for normal neural development, are lost, leading to microcephaly.
These results collectively suggest that neural stem cells need MSI1 to generate enough neurons for normal brain size, but the presence of MSI1 also increases the vulnerability of these cells to Zika infection, leading to the death of the population which ultimately results in microcephaly.
Dr Mike Turner, Head of Infection and Immunobiology at Wellcome, which funded the research along with Cancer Research UK, said: “This new finding really helps to explain why neural stem cells are so vulnerable to Zika infection.
“It will also be interesting to investigate whether this protein is involved in other viruses, such as Rubella, that can also access and impair the developing human brain.”
Main picture shows the mosquito Aedes aegypti, one of the transmitters the Zika virus.
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Jamie Johnston, Royal Society (Mar 2017), £15,000
Tom Bennett, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792
Richard Bayliss, Cancer Research UK (Jan 2017), £1,600,000
John Barr, EU (Jan 2017), £339,000
Mark Harris, Royal Society (Jan 2017), £250,000
Alison Dunn, NERC (Jan 2017), £105,000
Alex Breeze, Pancreatic Cancer Research Fund (Jan 2017), £180,000
Alison Dunn, NERC (Dec 2016), £18,000
Lisa Collins, BBSRC (Dec 2016), £1,681,835
Brendan Davies, Leverhulme Trust (Dec 2016), £247,555
Alan Benson, Mark Drinkhill, Ed White, British Heart Foundaion (Dec 2016), £217,223
Adrian Goldman, Royal Society (Dec 2016), £82,999
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, RCUK (Nov 2016), £484,172
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, Wellcome Trust (Nov 2016), £119,343
Katie Field, Rank Prize Funds (Nov 2016), £20,000
Jessica Kwok, Royal Society (Nov 2016), £14,948
John Ladbury, Cancer Research UK (Oct 2016), £4,250
Miriam Wittmann, Martin Stacey, Edward Vital, Lupus UK
(Oct 2016), £34,010
Valerie Speirs, NC3Rs
(Oct 2016), £90,000
Nicola Stonehouse, Morgan Herod, David Rowlands, BBSRC
(Sep 2016), £436,424
Joseph Cockburn, Wellcome Trust
(Sep 2016), £100,000
John Barr, Public Health England
(Sep 2016), £94,471
Helen Miller, DSM Nutritional Products A/S
(Sep 2016), £54,680
Steven Clapcote, Vitaflo International Ltd
(Sep 2016), £39,285
Juan Fontana Jordan De Urries
, Royal Society
(Sep 2016), £21,793
Jing Li, Sarah Calaghan, Mark Drinkhill, British Heart Foundation
(Sep 2016), £117,585
Sheena Radford, Alison Ashcroft, BBSRC (Sep 2016), £457,216
Patricija Van Oosten-Hawle, An-Jung Chen, David Westhead, NC3Rs
(Sep 2016), £354,456
Glyn Hemsworth, BBSRC (Sep 2016), £1,024,034