Document Type |
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Thesis |
Document Title |
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GENETIC DIVESITY OF MERS-COV IN CAMELS IMPORTED TO SAUDI ARABIA التنوع الجيني لفيروس متلازمة الشرق الأوسط التنفسية كورونا في الإبل المستوردة الى المملكة العربية السعودية |
Subject |
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Faculty of Science |
Document Language |
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Arabic |
Abstract |
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The Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is an endemic virus in Middle Eastern and African dromedaries. Annually, Saudi Arabia imports thousands of camels from the Horn of Africa, yet the epidemiology of the virus in these animals is largely unknown. Here, MERS-CoV prevalence was compared in imported African camels and their local counterparts. A total of 1399 paired sera and nasal swabs were collected between 2016 and 2018 from camels from Sudan (n=829), Djibouti (n=328) and Jeddah (n=242). Imported animals were sampled on incoming ships at Jeddah Islamic seaport before unloading. Samples were screened for neutralizing antibodies (nAbs), confirmed by enzyme linked immunosorbent assay (ELISA) and MERS-CoV viral RNA by RT-PCR. The overall seroprevalence was 92.7% and RNA detection rate was 17.2%. Imported camels had higher seroprevalence compared to resident herds (93.8% vs 87.6%, p <0.01) in contrast to RNA detection (13.3% vs 35.5%, p <0.0001). Seroprevalence significantly increased with age (p<0.0001) and viral RNA detection rate was ~2-folds in camels <2-year-old compared to older camels. RNA detection was higher in males verses females (24.3% vs 12.6%, p<0.0001) but seroprevalence was similar. Concurrent positivity for viral RNA and nAbs was found in >87% of the RNA positive animals, increased with age and was sex dependent. Importantly, reduced viral RNA load was positively correlated with nAb titers. Viral RNA extracted from respiratory samples and three MERS-CoV genome regions (ORF1a, Spike, and ORF4b) were amplified to generate genomic data before and after known Coronavirus recombination break-points and these were aligned with available MERS-CoV strains and clades A, B and C in GenBank. Alignments were made using MAFFT. Bayesian phylogeographic reconstructions were made using Beast 1.10.4 under assumption of a HKY nucleotide substitution model. Geographic locations were reconstructed at all tree nodes. Recombination analyses were made using SimPlot V3.5 and RDP V4.95. Social network analysis was based on Bayesian stochastic search variable selection, and correlation of genetic and geographic distance of strains performed to determine the extent to which virus transmission between countries after genetic lineage establishment has contributed to the present geographic distribution. All viruses from imported camels belonged to clade C. African MERS-CoV lineages in camels imported into KSA were not observed in camels in KSA. All KSA viruses belonged to a novel recombinant clade (NRC) first detected in 2014. R0 estimates informed by the sequences suggest sustained endemicity of NRC without introduction of new viruses from Africa. Analysis of population dynamics shows that Arabian viruses can maintain endemicity without introduction of additional lineages. African MERS-CoV lineages do not appear to establish themselves in camels in KSA. The higher detection rate of MERS-CoV RNA in camels from the Arabian Peninsula points toward differences in transmission dynamics and selection pressure. Further studies should focus on understanding potential changes in virulence and transmissibility. Our data confirm MERS-CoV widespread in imported and domestic camels in Saudi Arabia and highlight the need for continuous active surveillance and better prevention measures. Further studies are also warranted to understand the correlates of protection in camels for proper vaccine development. |
Supervisor |
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Dr. Saad Berki AL Masaudi |
Thesis Type |
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Doctorate Thesis |
Publishing Year |
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1441 AH
2019 AD |
Co-Supervisor |
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Prof. Esam Ibraheem Azhar |
Added Date |
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Wednesday, December 4, 2019 |
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Researchers
أحمد مجدي طوله | Tolah, Ahmed Majdi | Researcher | Doctorate | |
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