One of the many disturbing things about Ebola is that the virus has such a large peer group.

That peer group begins with its filovirus cousin, Marburg virus, and moves to the still closely related Arena viruses to viruses that are genetically not all that similar, but as bad or worse from a public health perspective – for example, the coronaviruses MERS-CoV and SARS-CoV.

How much worry such rare cases warrant from a public health perspective depends on many factors. How contagious a virus is right now is one of the more easily determined factors – any virus with pandemic potential needs to be able to spread through the air, as the flu virus does.

Of course, any virus that does not spread through the air might evolve to do so. The discovery that fewer than 10 mutations could allow the highly pathogenic H5N1 avian influenza strain to spread easily between ferrets led to a temporary moratorium on H5N1 research. And one of the reasons Ebola outbreaks are worrisome to public health officials is that one known strain, Ebola Reston, can spread through the air. (See BioWorld Today, June 25, 2012 , and Jan. 24, 2013.)

In the March 30, 2015, online issue of the Proceedings of the National Academy of Sciences, researchers have reported new structural insights into one viral family, the Henipa viruses.

The Henipa virus family is one of the newer contenders in the Viruses to Watch category. The first two families to be discovered in the 1990s were Hendra virus and Nipah virus. So far, no person-to-person cases have been reported for Hendra virus, while about half of all Nipah virus infections result from person-to-person contact.

How big of a problem Henipa virus family infections are is very hard to say. The main animal reservoir for both Hendra and Nipah virus is bats. Horses are an intermediate host for Hendra viruses, while Nipah virus spreads via pigs. There are only seven known cases of Hendra virus infection in humans. Nipah virus was identified in 1999 in an outbreak in Bangladesh that sickened 300 people and killed nearly 100. According to the Centers for Disease Control and Prevention, Nipah virus outbreaks "occur almost annually in Bangladesh and have been reported several times in India."

More recent research has turned up 19 more Henipa virus subtypes that are found not just in Australia and Asia, but also in Africa. How much of a problem those viruses are in terms of human infections is next to impossible to know. As senior author Benhur Lee of the Mount Sinai School of Medicine told BioWorld Today, the symptoms of Henipa virus infections are similar to those of any number of other viral illnesses including malaria, which still far outstrips Ebola virus or any other virus in terms of the number of people it sickens and kills in equatorial Africa.

"If you come down with fever and a headache in Sierra Leone, even to this day, your diagnosis will be malaria" – not Ebola, and certainly not Henipa virus.

Last November, Lee and his colleagues published work in Nature Communications demonstrating that antibodies to Henipa virus were present in almost half of all bats they examined, and about 4 percent of human samples they tested. Those findings demonstrated Henipa virus does spill over from bat populations into humans, most likely when bats are hunted for food.

The nature of the spillover illustrates another risk factor for pandemic viruses, namely, that they are more likely to originate from areas of social upheaval. Lee said that in his team's 2014 study looking for antibodies to Henipa-like viruses, "seropositive samples came from villages that were under ecological threat." The countries where the Ebola crisis continues are ones where civil society has been crippled by war and unrest. And one reason MERS-CoV is alarming is that it is originating in the Middle East, where a decade of unrest has left multiple countries on the road to failed statehood.

The current work, though, stuck to the cell biology of emerging viruses was focused on understanding how African Henipa virus binds the ephrinB receptor it uses to enter cells. The team found that although the Henipa virus they looked at has low sequence similarity to Hendra and Nipah virus sequences, the critical binding site adopts a very similar 3-D structure.

Beyond its specific findings on how the viruses enter cells, the paper also provides an example of how to do research on such viruses in a way that is less risky than working with the whole virus. Henipa viruses, like Ebola virus, are biosafety level (BSL) 4 agents, meaning that only a few laboratories are able to work with them at all, under the strictest of containment conditions.

Lee and his team expressed the Henipa proteins that are important for viral binding in another virus, vesicular stomatitis virus. Aside from alleviating safety concerns – as Lee said, "you can't treat every sample that comes up from the rainforest as a BSL4 sample, otherwise nothing will get done" – in the specific case of Henipa viruses, it is the only possibility to study the virus because the virus itself has not been isolated.

"Proof of their existence comes purely from sequence data," Lee said. "This is the brave new world of molecular biology."