Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus
- Permanent Link:
- Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus
- Series Title:
- Yang, Yang
Baric, Ralph S.
- Publication Date:
- Subjects / Keywords:
- Bat-To-Human Transmission ( local )
Mers ( local )
Mers Coronavirus ( local )
Bats ( local )
Coronavirus ( local )
Hku4 ( local )
- serial ( sobekcm )
- Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes âˆ¼36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikesâ€™ capability to adapt to human cells for cross-species transmissions. As of June 16, 2014, the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) had infected 701 people, with a fatality rate of âˆ¼36% (www.who.int/csr/don/2014_06_16_mers/en/), and had demonstrated the capability for human-to-human transmission (1, 2). Alarmingly, coronavirus surveillance studies have suggested that MERS-CoV originated from animals, with bats as the likely natural reservoir and camels as the likely intermediate hosts (3â‡“â‡“â€“6). Hence, cross-species transmission of MERS-CoV from bats to humans, either directly or through camels, poses a constant and long-term threat to human health.
- Original Version:
- PNAS, Vol. 111, no. 34 (2011-08-11).
- Source Institution:
- University of South Florida Library
- Holding Location:
- University of South Florida
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- This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the bounds of Fair Use or other exemptions to copyright law must be obtained from the copyright holder.
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