Study in Bats Suggests NPC1 May Play Role in Ebola

The African straw-colored fruit bat (Eidolon helvum) has evolved receptor cells that can resist the Ebola virus, and scientists say that the virus evolves in response.

A recently-published study  by Kartik Chandran, PhD, of the Department of Microbiology and Immunology at Albert Einstein College of Medicine in the Bronx, New York and colleagues and published in eLife illuminates how Ebola virus mutates, what bat species carry the deadly Ebola virus and how humans become infected, which could possibly assist in prevention efforts.

The straw-color fruit bat species, widespread in Africa and often hunted and consumed as bush meat, was previously thought to be responsible for spreading the disease.

The researchers examined cell lines from 4 species: the African straw-colored fruit bat, Büttikofer’s epauletted fruit bat (Epomops buettikoferi), Egyptian rousettes (Rousettus aegyptiacus), and the hammer-headed fruit bat (Hypsignathus monstrosus). Researchers infected cells with Ebola virus and other filoviruses.

The African straw-colored fruit bat was the only species with cell resistance to Ebola virus, which was linked to a change in 1 amino acid that prevents the virus from binding to the bat’s NPC1 receptor. Previous research has shown that this receptor is key to how Ebola infects cells.² However, the straw-colored fruit bat was not resistant to all filoviruses – researchers reported that all 4 bat species were susceptible to Marburg viruses, for example.

Dr Chandran and colleagues also observed the Ebola virus was 1 amino acid change away on its surface glycoprotein to potentially overcoming the resistance of the NPC1 receptor in the African straw-colored fruit bat. Scientists said this indicates a rapid molecular evolution race both in the virus and the bat’s cells, which may have been going on for 25 million years, twice the period of time previously thought.

Next, researchers determined after studying 13 bat species that the location on the NPC1 receptor where Ebola virus gains a foothold evolves much faster in bats than it does in humans or primates. They also noted that bat cells genetically altered to express the human version of NPC1 were more likely to have more virulent infection.

In an interview with Infectious Disease Advisor, Dr Chandran said the study “raises the possibility that differences in the gene under accelerated evolution in bats — the Ebola receptor NPC1 — could create barriers to the spread of Ebola from one type of bat to others, thereby affecting its distribution in nature.”

Dr Chandran continued, “the genetic approach we use in this study could be extended to identify new signatures of virus-host co-evolution in other types of animals, and provides one component of a biosurveillance strategy to pinpoint candidate reservoir species for Ebola and other emerging viruses. Such biosurveillance is crucial to mitigating risks for animal to human viral transmission.”

Dr Chandran concluded the interview by noting, “Our work suggests that the African straw-colored fruit bat, Eidolon helvum, is probably not the source of Ebola virus in the 2013–16 epidemic in West Africa,” and that the study “demonstrates that NPC1 is a valid target for development of antiviral therapeutics in humans” because it

“raises the possibility that NPC1 sequence polymorphisms render some humans resistant, or at least susceptible, to Ebola.”

References

1. Ng M, Ndungo E, Kaczmarek ME et al. Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats. eLife 2015;4:e11785. DOI: 10.7554/eLife.11785. Accessed January 1, 2015.

2. Herbert AS, Davidson C, Kuehne AI et al. Niemann-Pick C1 is essential for Ebolavirus replication and pathogenesis in vivo. mBio 6(3):e00565-15. DOI:10.1128/mBio.00565-15. Accessed January 1, 2015.