Predicting the next zoonotic outbreak
Coronaviruses have crossed the species barrier from animals into humans several times, each time outbreaks of severe, and sometimes fatal, respiratory illnesses. What is it about these novel viruses that enables them to readily infect humans? National Institute of Health experts, including Michael Letko and Bat OneHealth team member Vincent Munster, developed a new tool to test novel viruses for their ability to infect humans.
In the pre-print, Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV, the authors explain how they investigated the process by which lineage B betacoronaviruses, such as SARS-CoV and 2019-nCoV, invaded the cells of new host species.
The team synthesized fragments of viral genes that were then used to test the process by which viral spikes attach to a host cell. This sequencing was made possible through access to all published sequences in lineage B. In their pre-print, the authors explained that the synthesis of viral fragments was crucial in their ability to rapidly and cost-effectively screen viruses for their ability to infect new host species. Synthesizing complete viral sequences for novel CoVs would have taken weeks and been cost-prohibitive.
They found that protease processing by the host cell during viral entry was an important barrier for the invasion of several lineage B viruses into the host cells. Once this barrier had been overcome, several lineage B viruses were able to enter human cells through a second receptor that remains unknown. Their study also demonstrated how, once a cell had been invaded by several lineage B viruses, these could recombine into new variants that could infect human cells. Though the second receptor through which the viruses enter a human cell remains unknown, the researchers confirm that ACE2 is involved in the capacity of 2019-nCoV to infect humans. ACE2 is also a receptor involved in SARS infections.
Graphic from Figure 1 in Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV