Bats sighted this Halloween may not be quite as boo-tiful as they look. Bats have long been associated with haunted houses, spooky caves, and vampires. However, their nexus with the bloodcurdling and bone-chilling is not the only reason the masses fear them; they are also reservoirs for infectious disease. Now, researchers have been successful in isolating infectious influenza viruses from bats for the first time.
[bat infected with influenza A virus]
New research suggests that potential infection in humans with influenza A-like viruses from bats cannot be ruled out.
Image source: Albert Ludwigs Universität Freiburg

It is widely accepted that all known influenza A viruses originate from aquatic birds that serve as virus reservoirs in nature and can infect domestic poultry and other birds and animal species. While avian influenza A viruses usually do not infect humans, rare cares of human infection with these viruses have been reported.

Human infections with avian influenza viruses occur through eye, nose, or mouth contact with or inhalation of infected bird saliva, mucus, or feces. The resulting Illness in humans has ranged from mild to severe. Avian influenza A viruses have been isolated from more than 100 different species of wild birds.

While it is unknown whether additional animal reservoirs of influenza viruses exist, bats were recently identified as a potential new source of influenza A viruses.

Bat flu was first discovered in “little yellow-shouldered bats” in Guatemala in 2009 and 2010. Since then, bat flu viruses have been detected in other species of bat including fruit bats in Central and South America, where two unique genome sequences of influenza A-like viruses were identified provisionally labeled “HL17NL10” and “HL18NL11.” Comparisons between different bat flu viruses have shown considerable genetic diversity among them.

Breakthrough in isolating bat influenza viruses in laboratory

Previous preliminary laboratory research shows that human cells do not support the growth of bat flu viruses in the test tube, which suggests that bat flu viruses may not grow or replicate in humans and would, therefore, have to undergo significant changes to infect and spread among humans.

However, the discovery of bat flu was deemed important for public health, because bats represent a new animal species that may act as a source of flu viruses and a possible cause of pandemics if introduced to the human population. Flu viruses in animals – that gained the ability to infect and spread quickly in people – caused previous pandemics of the 20th century, in addition to the 2009 H1N1 pandemic.

Some bat-borne viruses including Marburg virus, Nipah virus, Hendra virus, SARS-CoV, and MERS-CoV have been able to cross the species barrier and cause severe disease in humans.

All current efforts to isolate infectious virus from bats to generate HL17NL10 and HL18NL11 by reverse genetics has previously failed. The team at the Institute of Virology at the University of Freiburg, Germany, together with scientists from Switzerland and the United States, however, now report a breakthrough in isolating a bat influenza virus by reconstituting fully functional bat influenza viruses in the laboratory. Reconstructing bat flu virus, they say, is essential for risk assessment.

The study – published online in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) – also unexpectedly found that the bat influenza viruses not only infected bat cells but also dog and human cells.

Scientists conducted the study by first identifying cells that are susceptible to bat flu infection – these cells need to express receptors on the cell surface for bat virus attachment and entry. The team screened more than 30 cell lines from different species to analyze their capacity to recognize and internalize bat influenza viruses, but only a few cell lines were found to be susceptible.

Human cells infected with vesicular stomatitis also susceptible to bat flu

Another virus, vesicular stomatitis virus, which can infect many cell types, was engineered to incorporate a bat influenza virus protein – typically used by the bat virus for entry into cells – on its surface.

The cell line most susceptible to the engineered vesicular stomatitis virus was used to reconstruct the original bat influenza A-like virus, starting with the known influenza-like viral genome sequences isolated from the bats.

“Infectious bat viruses were readily obtained. Interestingly, most cells, including human cells, that supported infection with the vesicular stomatitis indicator virus were also susceptible to direct infection with the reconstructed bat influenza virus,” explains Prof. Martin Schwemmle, group leader at the Institute of Virology in the Department for Medical Microbiology and Hygiene, University of Freiburg.

Schwemmle and colleagues say their finding that at least two human cell lines were susceptible to infection with HL18NL11 and HL17NL10 suggests that a potential infection in people with influenza A-like viruses from bats cannot be ruled out. Bats are natural hosts for highly pathogenic viruses, and evidence of past transmissions of Ebola and rabies from bats to humans have been shown to cause deadly disease.

Although there is no such evidence yet for transmissions of influenza A-like viruses from bats to humans, the researchers say that the new findings are a wake-up call for more investigation.

“It is too early to jump to definite conclusions on the ability of these viruses to cross the species barrier and infect humans but our studies make it possible now to conduct further experiments and analyze the risk that these viruses pose for other species.”

Prof. Martin Schwemmle

Experimental infection of bats will provide deeper insight into the viruses in the natural host and their mode of transmission. In the meantime, it may be best to avoid bats in costume or otherwise while out trick-or-treating tonight.

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