In 2012 a novel influenza virus was discovered in bats in South America, which was found to be divergent from the better-understood Influenza A viruses most commonly found in fowls and humans, although its exact mechanisms for infection – specifically how it infected animals, and to what extent it could potentially infect humans – were at the time poorly understood. Recently, however, researchers at the University of Zurich showed that these bat-influenza viruses have the potential to infect humans and livestock, albeit in a manner different from more thoroughly understood influenza strains. This potential for zoonotic transmission has of course raised the question of just how deftly the virus will spread between bats, livestock, and humans, and thus how likely a potential outbreak of the virus is to occur in human populations.
“Traditional” influenza A viruses in humans (as well as birds and some other animals) enter host cells by binding the virus’ hemagglutinin protein to the host cell’s sialic acid receptor, which are found on the surface of almost all human cells, as well as those of many different species of animals. In this study, Umut Karakus and his team at the University of Zurich have shown that the bat influenza A virus instead enters its host cell by binding hemagglutinin to a host cell’s major histocompatibility complex class II (MHC-II), which line epithelial cells in the upper respiratory tract. (Expression of MHC-II in URT epithelial cells are typically low, however their numbers typically increase in the event of a viral infection.) Notably, Karakus et al. observed that the MHC-II protein from several different species, including humans, mice, pigs, and chickens, all served as receptors to the bat influenza hemagglutinin molecule when expressed in human cells. The team stated: “Our data identify MHC-II as a crucial entry mediator for bat influenza A viruses in multiple species, which permits a broad vertebrate tropism.” Interestingly, influenza A’s neuraminidase protein, which influenza typically uses to remove sialic acid receptors from infected cells, serves an as yet unclear purpose in the bat influenza A virus.
The discovery of bat influenza A’s transmission and infection pathways of course leads to more questions that need answering. For example, it is remarkable that – given the ubiquity of MHC-II receptors in not only humans, but several species of animals, several of which are hosts to influenza A – we have not observed more bat influenza A infections in humans. It is entirely possible that, like avian influenza, bat influenza A currently does not spread well from human to human. However, because the virus is compatible for genetic exchange with human influenza viruses, the potential for a highly infectious strain is not out of the question. At present, we lack adequate data indicating just how widespread bat influenza really is, and by extension where or how likely a novel outbreak might occur. This does not preclude a significant event from occurring, however. We simply need more information – where the virus can be found and in which bat populations, its likelihood of spreading into livestock and humans – in order to mitigate any disastrous events. In other words, we still need to work toward a deeper understanding of bat influenza just as well as we understand other, more common influenza strains.
Jon Hamilton earned his Master’s Degree in Biohazardous Threat Agents and Emerging Infectious Diseases from Georgetown University. He was briefly involved in Healthcare Association of Hawaii’s Ebola Virus Disease Prevention working group during the 2014 EVD outbreak. He has also worked with and done research for infectious disease physicians in Honolulu and at the National Institutes of Health in Washington, D.C. When Jon is not researching or writing, he can be found surfing in sunny San Diego, California, where he currently resides. Jon can be reached on LinkedIn or at jonhamilt@gmail.com.
