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Tuesday, 21 August 2018

Adaptive Evolution Study of MERS-Coronavirus lead to the identification of Spike Attachment mutations that enhanced entry in non-permissive cell line

Middle East Respiratory Syndrome (MERS) – Coronavirus (CoV) has its importance due to its known high mortality rate of about 35% as declared by World Health Organization (WHO). This virus is known to be originated from bats and passed then to humans through zoonotic spill over events. Previously several species that support MERS-CoV infection had been studied but until this paper published in Cell Reports shows the genetic mechanisms underlying cross-species adaptation.

Letko et. al. studied the adaptive evolution of MERS-CoV using broad taxonomic distribution of BAT species. (Source Cell Reports)
The research was lead by Vincent Munster who is a virologist at NIAID, NIH, USA and also Michael Letko, a visiting research fellow at Munster’s lab. Munster is primarily interested in evolutionary dynamics of viruses and also cross species transmission events, and in this current research published recently in August 2018 has shown the impressive study on hoast breadth and adaptability of MERS-CoV.

Letko selected 16 bat species with broad taxonomic distribution to screen in vitro MERS-CoV entry based on transfected DPP4 expression in non-permissive cell line. Among 16 species only one species Desmodus rotundus DPP4 (drDPP4) had shown least permissive to viral replication. Letko carry forward to understand the differences in MERS Spike that is involved in interaction with DPP4 receptor. Homo sapiens DPP4 and drDPP4 was found to have differences in two amino acid locations I295T and R317T respectively. Later when they try to express these mutations in non-permissive cell lines show that these mutations are important to restrict virus entry.

Letko hypothesized that MERS-CoV can adapt to these variation while serially passaging the virus, where try to look into the cytopathic effects of the virus. Serially passaging the virus leading adaptation of the MERS-CoV was observed where they identified two important mutations in Spike which allow the virus to entry into cell lines which was non-permissive for wild type MERS-CoV.
Later team wanted to understand the phenotype of these mutations, which show that the adaptive virus has developed alteration of surface charge of Spike that allowed entry of MERS-CoV.

The team conclude its importance of the study is focused on virus endpoint study where there perform wide selection of specie where assessing host breadth. Although team suggests that during viral adaptation there might be continuous accumulation of other mutations apart from virus spike which remained unclear in their study.

Journal Source:

Letko M, Miazgowicz K, McMinn R, Seifert S, Sola I, Enjuanes L et al. Adaptive Evolution of MERS-CoV to Species Variation in DPP4. Cell Reports. 2018;24(7):1730-1737.

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