New Animal Virus Takes Northern Europe by Surprise

Scientists in northern Europe are scrambling to learn more about a new virus that causes fetal malformations and stillbirths in cattle, sheep, and goats. For now, they don't have a clue about the virus's origins or why it's suddenly causing an outbreak; in order to speed up the process, they want to share the virus and protocols for detecting it with anyone interested in studying the disease or developing diagnostic tools and vaccines.

The virus, provisionally named "Schmallenberg virus" after the German town from which the first positive samples came, was detected in November in dairy cows that had shown signs of infection with fever and a drastic reduction in milk production. Now it has also been detected in sheep and goats, and it has shown up at dozens of farms in neighboring Netherlands and in Belgium as well. According to the European Commission's Standing Committee on the Food Chain and Animal Health, cases have been detected on 20 farms in Germany, 52 in the Netherlands, and 14 in Belgium. Many more suspected cases are being investigated. "A lot of lambs are stillborn or have serious malformations," Wim van der Poel of the Dutch Central Veterinary Institute in Lelystad says. "This is a serious threat to animal health in Europe."

"We are taking this very, very seriously," adds Thomas Mettenleiter, head of the Friedrich-Loeffler-Institute (FLI), the German federal animal health lab located on the island of Riems. The virus appears to be transmitted by midges (Culicoides spp.), and infections likely occurred in summer and autumn of last year, but fetuses that were exposed to the virus in the womb are only now being born. The first cases of lambs with congenital malformations such as hydrancephaly - where parts of the brain are replaced by sacs filled with fluid - and scoliosis (a curved spine) appeared before Christmas. "Now, in some herds 20% to 50% of lambs show such malformations," Mettenleiter says. "And most of these animals are born dead."

Scientists are bracing for many more cases to appear, especially in cattle, because bovine fetuses infected in summer 2011 would be expected to be born in February and March.

Virologists have made some headway since they first announced the detection of the Schmallenberg virus in November. They have been able to isolate the virus and to culture it in insect and hamster cells. Evidence that it's responsible for the observed symptoms has become stronger with its isolation from brain tissue of affected lambs. "The characteristic malformations, together with the frequent virus detection in brains of malformed animals, clearly support a causal link," FLI's Martin Beer says. In a first animal experiment, scientists at FLI also infected three cows with the virus and showed that the virus replicated in them; one developed fever and diarrhea.

FLI researchers have already sequenced the genome of the new pathogen. Comparisons indicate it is a member of a group called the orthobunyaviruses. These viruses consist of three segments called S (short), M (middle), and L (long) and are mainly transmitted by mosquitoes and midges. Although the viruses are best known from Asia, some have been circulating in Europe for decades. Initially, scientists said the virus most closely resembled the Akabane virus, a pathogen that has been found in cattle, buffalo, sheep, camels, dogs, and other species, leading them to call it an "Akabane-like virus."

Now they say that at least the S segment of Schmallenberg's genome is most closely related to sequences of a different orthobunyavirus called Shamonda virus. Both Akabane and Shamonda virus belong to the so-called Simbu serogroup and are known to infect ruminants and to be transmitted by midges. But there are few orthobunyavirus sequences available with which to compare the new virus, so scientists are starting to sequence more members of the family. "Orthobunyaviruses have been neglected for a long time, and we just don't know a lot about them," says Jonas Schmidt-Chanasit of the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany.

A host of questions remains unanswered. Which vector species is transmitting the disease? Can animals infect each other directly? And of course, where did the virus come from? "The problem with orthobunyaviruses is that their segmented genome makes the emergence of new combinations very easy, just like with influenza viruses," Schmidt-Chanasit says. He points to a recent outbreak of a new orthobunyavirus in Peru. The pathogen, named Iquitos virus, turned out to have combined S and L segments of a known virus called Oropouche and the M segment of a new virus.

Whether the Schmallenberg virus could sicken humans is unknown. At least 30 orthobunyaviruses have been associated with human disease; the Oropouche virus, also a member of the Simbu serogroup, causes a febrile disease often associated with headaches, dizziness, skin rash, and malaise, whereas the Iquitos virus can cause diarrhea, vomiting, and nausea. But these viruses seem to be dependent on midges to infect humans and are not known to be directly transmitted from infected farm animals. Midges are less likely to bite humans than mosquitoes, and there have been no reports of unusual human illnesses from farmers whose livestock is infected.

A risk assessment by the European Centre for Disease Prevention and Control in Stockholm, issued just before Christmas, concluded that "it is unlikely that this new orthobunyavirus can cause disease in humans, but it cannot be excluded at this stage." But the experts recommended closely monitoring the health of farmers and vets.

In order not to lose time and to answer the most pressing questions fast, FLI has decided not to file for any patents on Schmallenberg-related discoveries. "Our resources are limited," Mettenleiter says, "and we are happy to share our knowledge and materials with anyone interested in it for noncommercial or commercial reasons." The German and Dutch institutes have divided up the work: The Dutch researchers will concentrate on sheep, Van der Poel says, while their German colleagues focus on cattle.