Middle East Respiratory Syndrome Coronavirus in Dromedaries in Ethiopia Is Antigenically Different From the Middle East Isolate EMC

Abstract

Middle East respiratory syndrome (MERS) is an emerging respiratory disease caused by the MERS coronavirus (MERS-CoV). MERS has been endemic to Saudi Arabia since 2012. The reservoir of MERS-CoV is the dromedary camel, suggesting that MERS is primarily a zoonotic disease. MERS-CoV is common in dromedaries throughout the Middle East, North Africa, and East Africa as evidenced by neutralizing antibodies against MERS-CoV; however, human cases have remained limited to the Middle East. To better understand the cause of this difference, the virological properties of African camel MERS-CoV were analyzed based on the spike (S) protein in Ethiopia. Nasal swabs were collected from 258 young dromedaries (≤ 2 years old) in the Afar region of Ethiopia, of which 39 were positive for MERS-CoV, as confirmed by genetic tests. All positive tests were exclusive to the Amibara woreda region. Using next-generation sequencing, two full-length genomes of Amibara isolates were successfully decoded; both isolates belonged to the C2 clade based on phylogenetic analysis of full-length and S protein sequences. Recombinant EMC isolates of MERS-CoV, in which the S protein is replaced with those of Amibara isolates, were then generated to test the roles of these proteins in viral properties. Amibara S recombinants replicated more slowly in cultured cells than in EMC S recombinants. In neutralizing assays, Amibara S recombinants were neutralized by lower concentrations of sera from both Ethiopian dromedaries and EMC isolate (wild-type)-immunized mouse sera, relative to the EMC S recombinants, indicating that viruses coated in the Amibara S protein were easier to neutralize than the EMC S protein. Neutralization experiments performed using S1/S2 chimeric recombinants of the EMC and Amibara S proteins showed that the neutralization profile was dependent on the S1 region of the S protein. These results suggest that the slower viral replication and the ease of neutralization seen in the Ethiopian MERS-CoV are due to strain-specific differences in the S protein and may account for the absence of human MERS-CoV cases in Ethiopia.

Spike proteins of novel MERS-coronavirus isolates from North- and West-African dromedary camels mediate robust viral entry into human target cells

“…Confirmation of our findings with authentic viruses is pending and we cannot exclude that, for instance, the S protein modulates recognition of the virus by sensors of the interferon system, which cannot be measured with the assays available to us. Moreover, we note that a recent study examining two MERS-S sequences (C2 subclade) from camels in Ethiopia demonstrated that these sequences, when inserted into MERS-CoV EMC, reduced viral entry and replication and increased sensitivity to antibody-mediated neutralization (Shirato et al, 2019). The reduction in entry was observed for Vero and to a lesser degree for Vero-TMPRSS2 cells and was generally modest.…”

Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

“…Thus, DPP4 polymorphisms could contribute to the perplexing absence of MERS cases in Africa, where the virus circulates in camels [52][53][54][55][56][57]. However, recent evidence suggests that sequence variations between African and Arabian MERS-CoV might be a factor [53,57]. More importantly, it remains to be analyzed how frequent DPP4 polymorphisms that affect S protein binding occur in the Middle East and whether they are associated with the clinical course of MERS.…”

A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains

“…Africa (8) and the Middle East (6) and seropositive dromedary camels have been found in Asia (20,21). Phylogenetic analyses show a clustering of MERS-CoV by geographical location (7,8) and analysis of 219 complete MERS-CoV genomes, which only included one African strain, showed the presence of two clades, with human isolates in both clades (22). Notably, antigenic differences have been reported between S proteins from the Middle East and Africa (7), potentially affecting the efficacy of a vaccine based on S protein.…”

“…MERS-CoV is mainly prevalent in the Arabian Peninsula, with the majority of cases occurring in KSA (84%) (5). However, phylogenetically diverse MERS-CoV strains have been isolated from Africa and the Middle East (6-8) and antigenic differences have been reported between spike (S) proteins, the main antigen utilized in MERS-CoV vaccines, from the Middle East and Africa (7).…”