Transmissibility of respiratory viruses
A brief update from virologist Sander Herfst, Department of Viroscience, Erasmus MC
Roughly 250.000 - 500.000 people die from flu or its consequences every year worldwide. The ordinary or seasonal flu is caused by an influenza A virus of the subtype H3N2 or H1N1 or an influenza B virus. Sometimes, however, influenza viruses from animals can mutate into viruses that can potentially cause a pandemic, which is a worldwide outbreak in humans. Fortunately there are researchers like Sander Herfst who work on this on a daily basis. With their research they try to understand how these viruses evolve, what can be done to recognize threats early and how vaccines against these new viruses can be developed.
Sander Herfst has worked for a long time at the Department of Viroscience at Erasmus MC, Rotterdam: in 1999 he started as an intern under supervision of professor Fouchier, developed further via a part-time job as a technician in the weekend and subsequently worked as a PhD student to obtain his doctorate in 2008, and now he works as a virologist. Sander is mainly interested in how respiratory viruses transmit, not only between humans, but also from animals to humans. An example of this is avian flu, certain variants of which are not only transmissible from bird to bird, but also from birds to humans.
Every virus mutates at a relatively high rate, and can mutate into variants that infect other animal species. But which properties in the virus make this transmission between mammals possible? How must a virus mutate to overcome the barrier from animals to humans or even humans to humans? This is the focus of Sander's research. The research results can help to estimate the potential risks of viruses for animals and humans and therefore contribute to the prevention of possible future outbreaks and pandemics.
PhD research focus on HMPV
Sander's PhD research focused on HMPV (human metapneumovirus), a respiratory virus that was discovered by researchers working at the Viroscience department in 2001 and that every child is infected with before the age of 5. HMPV is similar to HRSV (human respiratory syncytial virus) and causes a respiratory tract infection, sometimes associated with severe disease in young children, the elderly or immunocompromised individuals. Since the 1960s research has been done on HRSV in an effort to develop vaccines. However there is still no vaccine available against HRSV. For his PhD research, Sander designed and evaluated differerent vaccination strategies that may help to combat respiratory tract infection caused by HMPV.
'Change' of virus
"In 2008 I 'changed' viruses and started to focus on the influenza virus. And what made it really interesting for me was that in 2009 a new influenza virus emerged, the Mexican flu; official name A(H1N1)pdm09. Initially it was a virus that was only transmissible from pig to pig but then it suddenly also 'jumped' from pig to human, and from human to human. In such a situation you make a risk analysis: How dangerous is this virus? How pathogenic is it, or how capable is it of causing disease? Do existing anti-viral drugs still work against this new influenza virus? How efficiently is the virus transmitted via the air? And…in general, how can an influenza virus mutate in such a way that it can be transmitted from animals to humans and subsequently from humans to humans?"
A highly pathogenic H5N1 virus that could become airborne
Unlike the Mexican influenza, which luckily proved to be relatively mild, the H5N1 avian flu virus is potentially dangerous for humans. This virus causes large outbreaks in poultry in which it is extremely deadly. It is occasionally transmitted to humans, sometimes with fatal consequences. More importantly, every human infection in principle poses the risk that the virus mutates so that it can also be transmitted from human to human. A pandemic is therefore a constant risk with potentially serious consequences for public health.
"During our research we examined whether this H5N1 virus can become transmissible from ferret to ferret via the air. We use ferrets as a mammalian model system for humans. Ultimately this led to a scientific breakthrough: we were the first to demonstrate that a fully avian H5N1 virus could be transmitted via the air between mammals after the introduction of only a handful of mutations. With the publication of this research (Science, 2012), very important and urgent questions in influenza research were answered."
This project highlighted new fundamental details about genetic changes required for airborne transmission that had remained elusive so far. With collaborators at Cambridge University UK, Sander further showed that the individual airborne H5N1 mutations are already circulating in the field, and that the chance of airborne H5N1 virus emerging in the field is small, but not negligible (Science, 2012). Assisted by a PhD-student, he subsequently unravelled the genetic markers and associated phenotypic traits that rendered H5N1 virus transmissible (Cell, 2014). The accumulated knowledge on H5N1 virus was also applied to more translational research on H7N9 virus when this virus emerged in China in 2013, to show that this virus naturally acquired some airborne transmissibility, and shared mutations with airborne H5N1 virus (Nature 2013).
Sander is currently continuing this successful research line on influenza viruses as a co-PI on an NIH project (2014) and as PI on the new H2020 project VetBioNet (2016). In 2015 he received good news. All of the time and energy that he had invested in his research into the transmissibility of influenza viruses had been recognised. He received a prestigious Dutch Vidi grant worth 800,000 euros for his research.
Besides influenza virus, Sander is focusing in this research on the paramyxoviruses, including HMPV. Which similarities do these different respiratory viruses exhibit and how are they successfully transmitted from animal to animal and from human to human? The Vidi grant has allowed Sander to start his own research team consisting of himself, a PhD student and a technician.
- Airborne transmission of influenza A/H5N1 virus between ferrets.
Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Sorrell EM, Bestebroer TM, Burke DF, Smith DJ, Rimmelzwaan GF, Osterhaus AD, Fouchier RA.
Science. 2012 Jun 22;336(6088):1534-41.
- The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host.
Russell CA, Fonville JM, Brown AE, Burke DF, Smith DL, James SL, Herfst S, van Boheemen S, Linster M, Schrauwen EJ, Katzelnick L, Mosterín A, Kuiken T, Maher E, Neumann G, Osterhaus AD, Kawaoka Y, Fouchier RA, Smith DJ.Science. 2012 Jun 22;336(6088):1541-7.
- Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus.
Linster M, van Boheemen S, de Graaf M, Schrauwen EJ, Lexmond P, Mänz B, Bestebroer TM, Baumann J, van Riel D, Rimmelzwaan GF, Osterhaus AD, Matrosovich M, Fouchier RA, Herfst S.
Cell. 2014 Apr 10;157(2):329-39.
- Limited airborne transmission of H7N9 influenza A virus between ferrets.
Richard M, Schrauwen EJ, de Graaf M, Bestebroer TM, Spronken MI, van Boheemen S, de Meulder D, Lexmond P, Linster M, Herfst S, Smith DJ, van den Brand JM, Burke DF, Kuiken T, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. Nature. 2013 Sep 26;501(7468):560-3.