BENGALURU: A study by the Indian Institute of Science (IISc) has revealed why viruses like SARS-CoV-2, which originate in bats, cause severe disease in humans but not in bats.
The research shows how these viruses manipulate cell death and inflammation differently in humans and bats. The study found that SARS-CoV-2 uses a protein called Nsp13 to trigger excessive cell death in humans, leading to severe inflammation and tissue damage, such as lung damage seen in Covid-19. In bats, however, the same protein activates a controlled, less harmful cell death response, helping them tolerate the virus without getting seriously ill.
The study, led by Assistant Professor Kesavardana Sannula from the Department of Biochemistry, focuses on how zoonotic viruses - those transmitted from animals to humans - affect cell death in their hosts.
Cell death is a defense mechanism used by the body to stop viral replication, but excessive and uncontrolled cell death can lead to tissue damage and severe inflammation, worsening the disease.
SARS-CoV-2 uses a protein called Nsp13 to mimic certain components of the human cell death machinery. This protein contains RHIMs (RIP homotypic interaction motifs), which are critical for regulating cell death and inflammation.
By mimicking RHIMs, Nsp13 triggers an aggressive cell death in human proteins such as ZBP1 and RIPK3 to amplify tissue damage. This excessive immune response is believed to contribute to the respiratory complications and disease progression seen in Covid-19 patients.
In bats, however, the process is markedly different. While SARS-CoV-2’s Nsp13 can activate cell death in bat cells, the response is controlled and non-inflammatory.
This allows bats to effectively clear viral infections without triggering severe tissue damage. The researchers suggest that this restrained immune response is why bats can host viruses like SARS-CoV-2 without suffering from serious illnesses.