Scientists first discovered bat flu viruses in 2012. Although these were influenza A viruses, there was something strange about them – the way they infected their host’s cells seemed to be different from other influenza A viruses. Given the justified fear over zoonotic diseases (those that cross from animals to humans, such as bird flu), the race was on to discover how these viruses operated.
Scientists at the University of Zurich have just won that race. They recently reported in Nature that they have identified the gateway (“receptor”) that lets the bat flu viruses enter their host’s cells and cause infection. Unfortunately, this receptor also exists on the cells of certain livestock and, more worryingly, humans.
Flu viruses (of the non-bat variety) infect several livestock species by binding to a molecule called sialic acid on cells that line the respiratory tract of these animals. Similar receptors are also found on cells in the human respiratory tract, especially in the lungs, hence the spread of bird and swine flu to humans.
However, unlike livestock viruses, the two classes of bat flu virus discovered in 2012 in Latin America don’t bind to sialic acid receptors. This suggested that bat flu attaches and enters cells in a different way to classical flu viruses. In the new research from Switzerland, researchers discovered that the bat flu viruses enter their host’s cells via proteins on the cell surface called MHC-II. The finding is alarming because these protein receptors are very similar across a number of species, including mice, pigs and chickens.
To discover how bat flu infected cells, the researchers compared the genes that are activated in cells that are either resistant or susceptible to bat-borne flu infection. They initially identified ten important genes. Five of these genes were responsible for making MHC-II-associated proteins. They then used a genome editing technique to remove MHC-II proteins from the cell and noticed that bat flu failed to gain entry to the cells.
MHC-II proteins are found on the surface of certain immune cells, and they play an important role in discriminating the body’s own structures from pathogens, such as bacteria and viruses.
Because pigs and chickens are able to transmit conventional flu viruses to humans, researchers over-expressed MHC-II proteins from pigs and chickens into human cells. These hybrid cells became susceptible to bat flu, which suggests that the virus could infect chicken and pigs.
Because of the role farm animals play in transmitting flu to humans, it appeared that the bat flu virus has the potential to either infect humans directly or by first infecting other animals. But given the limited understanding of MHC-II in bats, the biological role of the protein in transmitting bat flu remains obscure and is yet to be investigated.
Dangerous disease spreaders
Bats make up 20% of all known mammals and are carriers of over 65 human pathogens including Ebola, SARS and Nipah viruses. These viruses have been transmitted from bats to humans either directly or through intermediate hosts. Intriguingly, viruses that can successfully spread and transmit between different bat species can also rapidly spread to people, indicating the risk bats pose in spreading zoonotic diseases.
We don’t know whether humans have been infected with bat flu in the past, but this research suggests that it is possible. The finding that MHC-II expression in the respiratory tract cells lets bat flu replicate, suggests that the virus could be transmitted to humans through the air. And given the presence of MHC-II receptors in different organs, the bat flu viruses could be spread by bat saliva, urine or faeces. This route of transmission is more likely because of increasing bat-human contact.
Like swine and bird flu, bat-borne flu viruses are widely prevalent around the globe and the newly identified route of entry is common in many farm animals, so the risk of bat flu infecting humans and livestock is probably high.
Importantly, because of increasing human contacts with wildlife, including bats, consumption of bat “bushmeat” and hunting bats for both food and money has exposed humans to the zoonotic spillover of viruses. In these events, the interaction of bat flu with MHC-II could potentially remove these important immune molecules and put people and animals at risk of other viral and bacterial infections, too.