Isolation and growth characterization of novel full length and deletion mutant human MERS-CoV strains from clinical specimens collected during 2015

Abstract

Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5′UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5′UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection.

An infectious cDNA clone of a growth attenuated Korean isolate of MERS coronavirus KNIH002 in clade B

“…The effect of these deletions in accessory ORFs of MERS-CoV and the molecular mechanism of biogenesis of these defective accessory ORF genes are unknown. Recently, more diverse deletion variants were detected in the clade B MERS-CoV isolates collected from patients in Saudi Arabia in 2015 [ 37 ]. The authors found deletions in the 5′-UTR, Nsp2 (in ORF1a), and ORF3.…”

Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2

“…The MERS-CoV genome is about 30,119 nucleotides in length and has a 5ʹ terminal cap structure and a poly (A) tail at the 3ʹ end. The genome encodes 16 non-structural proteins (nsp1–nsp16) at the 5ʹ end, four structural proteins (S, E, M, and N) at the 3ʹ end, 24 and five accessory proteins in ORF3, ORF4a, ORF4b, ORF5, and ORF8. 18 Risk factors for severe MERS-CoV include age and the presence of underlying conditions such as diabetes, obesity, hypertension, chronic renal disease, and lung diseases.…”

<p>Middle East Respiratory Syndrome – What Every Otolaryngologist Should Know: A Review</p>

“…The genome-wide nucleotide substitution rate of the virus between the camel and human strains is 4.81 × 10 −4 per site per year. 32 MERS-CoV is acquired by camels less than 1 year of age 33 and produces asymptomatic manifestations or mild respiratory symptoms that are difficult to conclusively diagnose. For example, in 2013, a case was reported of a camel with fever and rhinorrhea.…”