Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here, we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times, we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans. eLife digest Coronaviruses are one of many groups of viruses that cause the common cold, though some members of the group can cause more serious illnesses. The SARS coronavirus, for example, caused a widespread epidemic of pneumonia in 2003 that killed 774 people. In 2012, a new coronavirus was detected in patients from the Arabian Peninsula with severe respiratory symptoms known as Middle East respiratory syndrome (or MERS for short). To date the MERS coronavirus has also killed over 700 people (albeit over a number of years rather than months). Yet unlike the SARS coronavirus that spreads efficiently between humans, cases of MERS were rarely linked to each other or to contact with animals, with the exception of hospital outbreaks. Though camels were later identified as the original source of MERS coronavirus infections in humans, the role of these animals in the epidemic was not well understood. Throughout the epidemic nearly 300 genomes of the MERS coronavirus had been sequenced, from both camels and humans. Previous attempts to understand the MERS epidemic had either relied on these data or reports of case numbers but led to conflicting results, at odds with other sources of evidence. Dudas et al. wanted to work out how many times the MERS coronavirus had been introduced into humans from camels. If it happened once, this would indicate that the virus is good at spreading between humans and that treating human cases should be a priority. However, if every human case occurred as a new introduction of the MERS coronavirus from camels, this would mean that the human epidemic would not stop until the virus is controlled at the source, that is, in camels. Many scientists had argued that the second of these scenarios was most likely, but this had not been strongly demonstrated with data. By looking at the already sequenced genomes, Dudas et al. worked out how the MERS coronaviruses were related to each other, and reconstructed their family tree. Information about the host from which each sequence was collected was then mapped on the tree. Unlike previous attempts to complete this kind of analysis, Dudas et al. took an approach that could deal with the viruses in camels being more diverse than those in humans. Consistent with the scenario where human cases occurred as new introductions from camels, the analysis showed that the MERS coronavirus populations is maintained exclusively in camels and the viruses seen in humans are evolutionary dead-ends. This suggests that MERS coronavirus spreads poorly between humans, and has instead jumped from camels to humans hundreds of times since 2012. As well as providing data to confirm a previously suspected hypothesis, these findings provide more support to the current plans to mitigate infections with MERS coronavirus in the Arabian Peninsula by focusing control efforts on camels.
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