Bats are critical reservoirs of zoonotic viruses, including coronaviruses, lyssaviruses, filoviruses and paramyxoviruses. Zoonotic retroviruses are one the most impactful viral families to jump from animals to humans. Retroviral infections in humans and animals are often oncogenic (cancer-causing). Retroviral replication involves the insertion of proviral DNA into the host genome, typically leading to oncogenesis when insertion disrupts the expression of cellular oncogenes.
Recently, the first confirmed infectious bat retrovirus, Hervey pteropid gammaretrovirus (HPG), was discovered in the Australian black flying fox (Pteropus alecto). HPG is closely related to the gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV), both of which cause blood cancers in their hosts. Notably, HPG has been reported in a bat with leukemia, suggesting that HPG may also be oncogenic. Whether HPG can cause cancer in bats or other mammalian hosts is not presently known. In vitro studies have shown that HPG can establish persistent infection in human cells and utilises the PiT-1 receptor, which is highly conserved between species and widely expressed across mammalian tissues, suggesting that it may pose a zoonotic threat to humans.
In this study, we investigated whether HPG infection in human and bat cell lines will alter the expression of cancer-related genes. HPG infected cells were repeatedly passaged in human and bat cell lines, demonstrating that HPG can establish a persistent infection in the cells of both species. Total RNA was extracted following infection and compared to uninfected cells through RNA-seq. Gene expression and pathway enrichment analyses demonstrated that HPG infection of both bat and human cells impacted many cancer- and specifically leukemia related genes and gene pathways commonly dysregulated during cancer development. These findings support the hypothesis that HPG is an oncogenic retrovirus, which may potentially cause blood cancer in humans and bats.