Bat viruses and antiviral factors

Open to students

Bats are infamous reservoirs of deadly human viruses including Ebola, SARS-CoV-2 and Hendra virus. The impact of the global COVID-19 pandemic demands that we pay closer attention to viruses hosted by bats and their potential as an emerging threat. We have discovered Hervey pteropid gammaretrovirus (HPG), the first replication competent retrovirus circulating in Australian fruit bats.

While retroviruses, such as HIV, are among the most significant of virus families that have jumped from animals to humans, whether bat retroviruses have the potential to infect and cause disease directly to humans remains unknown.

We have also characterised antiviral proteins in bats that are distinct and more diverse compared to counterparts in other species including humans. Our discovery suggests that bats are forearmed to deal with multiple viral threats.

Objective

We aim to increase our understanding of bat retroviruses to address public health and global infectious disease threats a well as the interplay between bat antiviral factors and bat viruses to understand how bats harbour viruses without showing clinical signs of disease.

Approach

The host range of HPG will be determined by experimental infection of primary cells and cell lines from different species. Ability of bat antiviral factors to inhibit virus replication, and their mechanism of action, will be performed in cell culture-based assays.

Community impact

Bats can harbour viruses without showing clinical signs of disease. Understanding how bats can co-exist with viruses can hold the key to treating viral infections in other hosts including humans. This project will also increase our fundamental understanding of bat retroviruses and could have public health implications, as bats are hunted for bush meat in many countries.

Student opportunities

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Bat antiviral defenses against viruses

Bats are a major reservoir of viruses such as Hendra virus, Ebola virus, and coronaviruses that are pathogenic in humans but not in bats. The reason why bats can coexist with these viral pathogens is unknown. However, one explanation is that the coevolution of bats and their viruses has resulted in a ‘peace treaty’, a biological equilibrium in which viral replication is regulated in such a way that both host and virus can co-exist without undue antagonism.

The role of the host’s immune system is to control infections and antiviral restriction factors are at the front line of the innate immune response that targets viruses. These antiviral restriction factors were originally discovered to restrict retroviruses from other mammalian species, such as HIV (Hayward et al 2018 Mol Biol Evol 35:7) and some of these factors e.g. tetherin (Hayward et al 2022 J Virol 96:e0115222), can additionally restrict paramyxoviruses, coronaviruses and filoviruses.

Bats have recently been found to be an important reservoir of retroviruses from the genus Gammaretrovirus and are involved in transmission of retroviruses between mammalian species. The genomic fossil record of endogenous retroviral sequences, which are present as a critical part of eukaryotic genomes, also indicates that bats have a long history of infection with gammaretroviruses and betaretroviruses indicating that retroviruses have circulated in bats throughout their evolutionary history (Hayward and Tachedjian 2021 mBio).

How the innate immune system of bats has adapted to tolerate or combat infection with retroviruses remains largely unexplored. This project seeks to further characterise the interactions between bat restriction factors and the Hervey pteropid gammaretrovirus, the first extant retrovirus discovered in bats (Hayward et al 2020 PNAS 117:17).

This is a joint project between the Tachedjian Lab and CSIRO Australian Animal Health Laboratory.