Abstract
Bats are natural hosts for numerous zoonotic viruses, including henipaviruses, which are highly pathogenic for humans, livestock, and other mammals but do not induce clinical disease in bats. Pteropus bats are identified as a reservoir of henipaviruses and the source of transmission of the infection to humans over the past 20 years. A better understanding of the molecular and cellular mechanisms allowing bats to control viral infections requires the development of relevant, stable, and permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a combination of ESRRB (Estrogen Related Receptor Beta), CDX2 (Caudal type Homeobox 2), and c-MYC (MYC proto-oncogene) transcription factors, we generated bat reprogrammed cells. These cells exhibit stem cell-like characteristics and neural stem cell molecular signature. In contrast to primary fibroblastic cells, these reprogrammed stem cells are highly permissive to henipaviruses and exhibit specific transcriptomic profiles with the particular expression of certain susceptibility factors such as interferon-stimulated genes (ISG), which may be related to viral infection. These Pteropus bat reprogrammed stem cells should represent an important experimental tool to decipher interactions during henipaviruses infection in Pteropus bats, facilitate isolation and production of bat-borne viruses, and to better understand the bat biology.
Highlights
To obtain bat primary cell cultures, samples were dissected in a Petri dish and explants derived from the trachea (PTCs), lung (PLCs), and alary membrane (PACs) were cultured at 37 ◦ C/7% CO2 in gelatin-coated wells containing either fibroblast medium (FM)
Since the respiratory system is the route for henipaviruses in susceptible species, the trachea and lungs were sampled during entry route for henipaviruses in susceptible species, the trachea and lungs were sampled a necropsy
We investigated whether generated bat PCs (bPCs) were permissive to henipaviruses infection. bPCs were infected with two human isolates of Nipah virus: Nipah Malaysia (NiV-M) and Nipah Bangladesh (NiV-B) at a high multiplicities of infection (MOI) of 3. 24 h post-infection, few foci of infected cells were detected in the three types of bPCs while all human Hela cells, used as a positive control, were infected (Figure 1c)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The emergence of zoonotic diseases is increasing globally; the ability to predict and prevent viral epidemics is a major objective for public health organizations. Among all emerging infectious diseases, approximately 60% are of zoonotic origin [1] and bats are largely responsible for many of them as hosting a higher number of human and animal zoonotic viruses compared to other mammals [2,3].
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