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Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study.

ABSTRACT: BACKGROUND:Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic infection causing severe viral pneumonia, with index cases having resided in or recently travelled to the Arabian peninsula, and is a global concern for public health. Limited human-to-human transmission, leading to some case clusters, has been reported. MERS-CoV has been reported in dromedary camels but phenotypic characterisation of such viruses is limited. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. METHODS:We characterised MERS-CoV viruses from dromedaries in Saudi Arabia and Egypt and compared them with a human MERS-CoV reference strain. We assessed viral replication kinetics and competence in Vero-E6 cells (rhesus monkey), tissue tropism in cultures of ex-vivo human bronchial and lung tissues, and cytokine and chemokine induction, gene expression, and quantification of viral RNA in Calu-3 cells (human respiratory tract). We used mock-infected tissue as negative controls for ex-vivo experiments and influenza A H5N1 as a positive control for cytokine and chemokine induction experiments in Calu-3 cells. FINDINGS:We isolated three dromedary strains, two from Saudi Arabia (Dromedary/Al-Hasa-KFU-HKU13/2013 [AH13] and Dromedary/Al-Hasa-KFU-HKU19D/2013 [AH19D]), and one from Egypt (Dromedary/Egypt-NRCE-HKU270/2013 [NRCE-HKU270]). The human and dromedary MERS-CoV strains had similar viral replication competence in Vero-E6 cells and respiratory tropism in ex-vivo cultures of the human respiratory tract, and had similar ability to evade interferon responses in the human-respiratory-tract-derived cell line Calu-3. INTERPRETATION:The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. Exposure to zoonotic MERS-CoV is probably occurring in a wider geographical region beyond the Arabian peninsula. FUNDING:King Faisal University, Egyptian National Research Centre, Hong Kong Food and Health Bureau, National Institute of Allergy and Infectious Diseases, and European Community Seventh Framework Program.

SUBMITTER: Chan RW

PROVIDER: S-EPMC7164818 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study.

Chan Renee W Y RW Hemida Maged G MG Kayali Ghazi G Chu Daniel K W DK Poon Leo L M LL Alnaeem Abdelmohsen A Ali Mohamed A MA Tao Kin P KP Ng Hoi Y HY Chan Michael C W MC Guan Yi Y Nicholls John M JM Peiris J S Malik JS

The Lancet. Respiratory medicine 20140828 10

<h4>Background</h4>Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic infection causing severe viral pneumonia, with index cases having resided in or recently travelled to the Arabian peninsula, and is a global concern for public health. Limited human-to-human transmission, leading to some case clusters, has been reported. MERS-CoV has been reported in dromedary camels but phenotypic characterisation of such viruses is limited. We aimed to compare MERS-CoV isolates from dromed ...[more]

PMID: 25174549

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Project description:Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic disease. Exposure to dromedary camels (Camelus dromedaries) has been consistently considered the main source of primary human infection. Although Saudi Arabia reports the highest rate of human MERS-CoV infection and has one of the largest populations of dromedary camels worldwide, their spatial association has not yet been investigated. Thus, this study aimed to examine the correlation between the spatial distribution of primary MERS-CoV cases with or without a history of camel exposure reported between 2012 and 2019 and dromedary camels at the provincial level in Saudi Arabia. In most provinces, a high proportion of older men develop infections after exposure to camels. Primary human infections during spring and winter were highest in provinces characterized by seasonal breeding and calving, increased camel mobilization and camel-human interactions. A strong and significant association was found between the total number of dromedary camels and the numbers of primary camel-exposed and non-exposed MERS-CoV cases. Furthermore, spatial correlations between MERS-CoV cases and camel sex, age and dairy status were significant. Via a cluster analysis, we identified Riyadh, Makkah and Eastern provinces as having the most primary MERS-CoV cases and the highest number of camels. Transmission of MERS-CoV from camels to humans occurs in most primary cases, but there is still a high proportion of primary infections with an ambiguous link to camels. The results from this study include significant correlations between primary MERS-CoV cases and camel populations in all provinces, regardless of camel exposure history. This supports the hypothesis of the role of an asymptomatic human carrier or, less likely, an unknown animal host that has direct contact with both infected camels and humans. In this study, we performed a preliminary risk assessment of prioritization measures to control the transmission of infection from camels to humans.

Project description:BackgroundThe Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen endemic to the Arabian Peninsula. Dromedary camels are a likely source of infection and the virus probably originated in Africa. We studied the genetic diversity, geographical structure, infection prevalence, and age-associated prevalence among camels at the largest entry port of camels from Africa into the Arabian Peninsula.MethodsIn this prospective genomic study, we took nasal samples from camels imported from Sudan and Djibouti into the Port of Jeddah in Jeddah, Saudi Arabia, over an almost 2-year period and local Arabian camels over 2 months in the year after surveillance of the port. We determined the prevalence of MERS-CoV infection, age-associated patterns of infection, and undertook phylogeographical and migration analyses to determine intercountry virus transmission after local lineage establishment. We compared all virological characteristics between the local and imported cohorts. We compared major gene deletions between African and Arabian strains of the virus. Reproductive numbers were inferred with Bayesian birth death skyline analyses.FindingsBetween Aug 10, 2016, and May 3, 2018, we collected samples from 1196 imported camels, of which 868 originated from Sudan and 328 from Djibouti, and between May 1, and June 25, 2018, we collected samples from 472 local camels, of which 189 were from Riyadh and 283 were from Jeddah, Saudi Arabia. Virus prevalence was higher in local camels than in imported camels (224 [47·5%] of 472 vs 157 [13·1%] of 1196; p<0·0001). Infection prevalence peaked among camels older than 1 year and aged up to 2 years in both groups, with 255 (66·9%) of 381 positive cases in this age group. Although the overall geographical distribution of the virus corresponded with the phylogenetic tree topology, some virus exchange was observed between countries corresponding with trade routes in the region. East and west African strains of the virus appear to be geographically separated, with an origin of west African strains in east Africa. African strains of the virus were not re-sampled in Saudi Arabia despite sampling approximately 1 year after importation from Africa. All local Arabian samples contained strains of the virus that belong to a novel recombinant clade (NRC) first detected in 2014 in Saudi Arabia. Reproduction number estimates informed by the sequences suggest sustained endemicity of NRC, with a mean Re of 1·16.InterpretationDespite frequent imports of MERS-CoV with camels from Africa, African lineages of MERS-CoV do not establish themselves in Saudi Arabia. Arabian strains of the virus should be tested for changes in virulence and transmissibility.FundingGerman Ministry of Research and Education, EU Horizon 2020, and Emerging Diseases Clinical Trials Partnership.

Dataset Information

Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study.

Publications

Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study.

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