MersV1, Main, Exploration, bibRecord, 001B08

Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus.

Identifieur interne : 001B08 ( Main/Exploration ); précédent : 001B07; suivant : 001B09

Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus.

Auteurs : Yang Yang [États-Unis] ; Lanying Du [États-Unis] ; Chang Liu [États-Unis] ; Lili Wang [États-Unis] ; Cuiqing Ma [États-Unis] ; Jian Tang [États-Unis] ; Ralph S. Baric [États-Unis] ; Shibo Jiang [États-Unis] ; Fang Li [États-Unis]

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2014.

RBID : pubmed:25114257

Descripteurs français

English descriptors

KwdEn :
- Animals, Chiroptera (virology), Coronavirus (classification), Coronavirus (pathogenicity), Coronavirus (physiology), Coronavirus Infections (transmission), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (physiology), Disease Reservoirs (virology), Host Specificity, Host-Pathogen Interactions, Humans, Middle East, Receptors, Virus (physiology), Respiratory Tract Infections (transmission), Respiratory Tract Infections (virology), Spike Glycoprotein, Coronavirus (physiology), Virulence, Virus Internalization.
MESH :
- chemical , physiology : Dipeptidyl Peptidase 4, Receptors, Virus, Spike Glycoprotein, Coronavirus.
- geographic : Middle East.
- classification : Coronavirus.
- pathogenicity : Coronavirus.
- physiology : Coronavirus.
- transmission : Coronavirus Infections, Respiratory Tract Infections.
- virology : Chiroptera, Coronavirus Infections, Disease Reservoirs, Respiratory Tract Infections.
- Animals, Host Specificity, Host-Pathogen Interactions, Humans, Virulence, Virus Internalization.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ∼ 36% 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 spikes' capability to adapt to human cells for cross-species transmissions.

DOI: 10.1073/pnas.1405889111
PubMed: 25114257

Affiliations:

Le document en format XML

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<term>Coronavirus (physiology)</term>
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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ∼ 36% 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 spikes' capability to adapt to human cells for cross-species transmissions.</div>
</front>
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Serveur d'exploration MERS

Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus.

Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus.

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Descripteurs français

English descriptors

Abstract

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