̽��ֱ�� of Cambridge - Zika

New insights into how the Zika virus causes brain birth defect

cjb250 — Thu, 01 Jun 2017 18:00:56 +0000

A study published today in Science shows that the Zika virus hijacks a human protein called Musashi-1 (MSI1) to allow it to replicate in, and kill, neural stem cells. 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. ̽��ֱ��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. Today’s study is the first to associate MSI1 with microcephaly and the Zika virus.

Dr Fanni Gergely from the Cancer Research UK (CRUK) Cambridge Institute at the ̽��ֱ�� of Cambridge said: “ ̽��ֱ��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.”

Dr Mike Turner, Head of Infection and Immunobiology at Wellcome said: “This is the first study to show a clear link between a specific protein, the Zika virus and microcephaly. This new finding really helps to explain why neural stem cells are so vulnerable to Zika infection and I hope this can be a first step in determining how we could stop this interaction and disease. It will also be interesting to investigate whether this protein is involved in other viruses, such as Rubella, that also access and impair the developing human brain.”

Researchers from the CRUK Cambridge Institute, together with colleagues at the ̽��ֱ��’s Department of Pathology and the Cambridge Institute for Medical Research, studied a variety of cell lines, including human neural stem cells, to investigate how Zika virus infection can lead to microcephaly. They suspected that MSI1 – and RNA binding protein - might be important in this process because it is involved in regulating the pool of neural stem cells that are required for normal brain development.

̽��ֱ��researchers show that when the Zika virus enters these stem cells, it hijacks MSI1 for its own replication and damages the cells in at least two ways. Firstly, MSI1 binds to the Zika virus genome allowing it to replicate and making the cells more vulnerable virus-induced cell death. When the researchers infected cells that had been rendered unable to produce MSI1, virus replication was significantly reduced, as was cell death, indicating that the presence of MSI1 is required for efficient Zika replication.

Secondly, they showed that MSI1 also disrupts the normal development programme of neural stem cells. In cells infected with Zika virus MSI1 binds to the virus genome in favour of its normal targets in the cell. ̽��ֱ��virus essentially acts like a ‘sponge’, preventing MSI1 from working correctly and altering the expression of many genes involved in neuronal development.

In both of these scenarios, neural stem cells, which are crucial for normal neural development, are lost, leading to reduced brain size.

To confirm that MSI1 is important to grow a normal size brain, the scientists demonstrated that MSI1 is mutated in individuals with a rare type of inherited microcephaly (autosomal recessive primary microcephaly) unrelated to Zika infection.

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.

This study was funded by Wellcome and Cancer Research UK.

Reference
Chavali, PL et al. Neurodevelopmental protein Musashi 1 interacts with the Zika genome and promotes viral replication. Science; 1 June 2017; DOI: 10.1126/science.aam9243

Adapted from a press release from Wellcome

Scientists have uncovered why Zika virus may specifically target neural stem cells in the developing brain, potentially leading to microcephaly – a potentially serious birth defect where the brain fails to develop properly, leading to a smaller head.

We hope that in the future this discovery could lead to ways of generating potential Zika virus vaccines

Fanni Gergely

Sumaia Villela/Agência Brasil

Baby with microcephaly

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution

Zika warnings lead to ‘significant’ increase in demand for abortions in Latin America

cjb250 — Wed, 22 Jun 2016 21:00:51 +0000

However, in many of these countries, abortion is either illegal or highly restricted, leaving pregnant women with few options and potentially driving women to use unsafe methods, access abortion drugs without medical supervision or visit underground providers.

On 17 November 2015, the Pan American Health Organization (PAHO) issued an alert about the Zika virus in Latin America. Although the virus, spread by mosquitos, causes only mild symptoms, it can have serious complications for unborn children, ranging from eye and hearing defects through to microcephaly (abnormally small heads) and other severe fetal brain defects. Following the PAHO alert, several countries issued health advisory warnings, including urging women to avoid pregnancy.

For several years, one option for women seeking an abortion in Latin America has been Women on Web, a non-profit organisation that provides medical abortion outside the formal healthcare setting through online telemedicine, in countries where safe abortion is not universally available. A team of researchers from the US and UK analysed data on requests for abortion through the website between 1 January 2010 and 2 March 2016 in 19 Latin-American countries, assessing whether requests for abortion increased beyond expected trends following the PAHO alert.

̽��ֱ��researchers found that in almost all of the countries that had issued health warnings about Zika and had legal restrictions on abortions, the number of requests for abortion through Women on Web rose significantly – effectively doubling in Brazil, Ecuador and Venezuela, and increasing by over a third in most of the other countries. In countries that had issued no health warnings, there was no statistically-significant increase.

Assistant Professor Abigail Aiken from the ̽��ֱ�� of Texas at Austin, said: “Accurate data on the choices pregnant women make in Latin America is hard to obtain. If anything, our approach may underestimate the impact of health warning on requests for abortion, as many women may have used an unsafe method or visited local underground providers.”

Dr Catherine Aiken from the Department of Obstetrics & Gynaecology at the ̽��ֱ�� of Cambridge added: “ ̽��ֱ��World Health Organization predicts as many as four million Zika cases across the Americas over the next year, and the virus will inevitably spread to other countries. It isn’t enough for health officials just to warn women about the risks associated Zika – they must also make efforts to ensure that women are offered safe, legal, and accessible reproductive choices.”

̽��ֱ��research was supported by the National Institutes of Health and the National Science Foundation.

Reference
Aiken, ARA et al. Requests for Abortion in Latin America in the Wake of Zika Virus. NEJM; 22 June 2016. DOI: 10.1056/NEJMc1605389

Declaration of interests
Rebecca Gomperts is Founder and Director of Women on Web. James Trussell serves on the Advisory Board of Women on Web. Marc Worrell is an IT Consultant for Women on Web.

Health warnings about complications related to Zika virus significantly increased demand for abortions in Latin American countries, according to a new study published today in the New England Journal of Medicine.

It isn’t enough for health officials just to warn women about the risks associated Zika – they must also make efforts to ensure that women are offered safe, legal, and accessible reproductive choices

Catherine Aiken

Pan American Health Organization

Sin Zancudos no hay Zika - Cúcuta

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution-Noncommerical

Uninfected or asymptomatic? Diagnostic tests key to forecasting major epidemics

cjb250 — Tue, 05 Apr 2016 18:00:00 +0000

Emerging epidemics pose a significant threat to human health worldwide. A principal challenge in infectious disease epidemiology is accurately forecasting the threats posed by diseases early in emerging outbreaks. Accurate real-time forecasts of whether or not initial reports of cases of disease will be followed by a major outbreak – an epidemic in which large numbers of people become infected – are necessary to determine which control measures should be deployed.

For all infectious diseases, there is a delay between infection and the appearance of symptoms, known as the ‘incubation period’, during which infected individuals are classed as ‘presymptomatic’. ̽��ֱ��incubation period, say researchers from the Department of Plant Sciences at Cambridge, can drive significant uncertainty in forecasting during the earliest stages of epidemics.

In research funded by the Biotechnology and Biological Sciences Research Council, the team used mathematical modelling to evaluate the effect of presymptomatic infection on predictions of major epidemics, choosing the Ebola virus as a case study. Their results, published today in the online journal PLOS Computational Biology, show for the first time that precise estimates of the current number of infected individuals – and consequently the chance of a major outbreak in the future – cannot be inferred from data based on symptomatic cases alone. This is the case even if factors such as the average infection rate and the death or recovery rates of individuals in the population can be estimated accurately.

“If we are able to use diagnostic tests to determine whether individuals who do not show symptoms are susceptible or are instead infected but not showing symptoms, we’ll be in a better position to estimate the chance of a major outbreak,” says Dr Nik Cunniffe, who led the study. “Since the reliability of diagnostic tests affects the extent to which forecasting is possible, it’s important not just to develop new diagnostic tests, but also to ensure those we have are continually refined and promptly deployed.”

Although the researchers chose Ebola as a representative case study of a disease for which reports of initial cases are not always followed by a large epidemic, they say their results are applicable to other outbreaks, including not just those that affect humans.

“These findings – that accurate forecasting relies on informing models with data on presymptomatic infections – hold true for anything from the current Zika outbreak through to animal diseases such as bluetongue and even plant pathogens such as Xylella fastidiosa, that is currently causing such devastation to olive groves in southern Italy,” adds first author Robin Thompson, a former PhD student at the Department of Plant Sciences, and now a postdoctoral researcher at the ̽��ֱ�� of Oxford.

̽��ֱ��researchers acknowledge that their models are based on an idealised setting, in which symptomatic cases and deaths were recorded perfectly and in which the values of disease transmission parameters were known exactly. However, they say that additional uncertainty will only make forecasting even more challenging. Presymptomatic infection alone makes prediction imprecise, reinforcing the need to better estimate levels of hidden infection in populations using diagnostic testing.

Reference
Thompson, RN, Gilligan, CA, Cunniffe, NJ. Detecting Presymptomatic Infection Is Necessary to Forecast Major Epidemics in the Earliest Stages of Infectious Disease Outbreaks. PLOS Computational Biology; 5 April 2016; DOI: 10.1371/journal.pcbi.1004836

Major epidemics such as the recent Ebola outbreak or the emerging Zika epidemic may be difficult to forecast because of our inability to determine whether individuals are uninfected or infected but not showing symptoms, according to a new study from the ̽��ֱ�� of Cambridge. ̽��ֱ��finding emphasises the need to develop and deploy reliable diagnostic tests to detect infected individuals whether or not they are showing symptoms, say the researchers.

If we are able to use diagnostic tests to determine whether individuals who do not show symptoms are susceptible or are instead infected but not showing symptoms, we’ll be in a better position to estimate the chance of a major outbreak

Nik Cunniffe

DFID - UK Department for International Development

Ultra-violet screening for potentially Ebola-carrying liquids (cropped)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution