S-Acylation of Proteins of Coronavirus and Influenza Virus: Conservation of Acylation Sites in Animal Viruses and DHHC Acyltransferases in Their Animal Reservoirs.

Dina A Abdulrahman,Xiaorong Meng,Michael Veit

doi:10.3390/pathogens10060669

Abstract

Recent pandemics of zoonotic origin were caused by members of coronavirus (CoV) and influenza A (Flu A) viruses. Their glycoproteins (S in CoV, HA in Flu A) and ion channels (E in CoV, M2 in Flu A) are S-acylated. We show that viruses of all genera and from all hosts contain clusters of acylated cysteines in HA, S and E, consistent with the essential function of the modification. In contrast, some Flu viruses lost the acylated cysteine in M2 during evolution, suggesting that it does not affect viral fitness. Members of the DHHC family catalyze palmitoylation. Twenty-three DHHCs exist in humans, but the number varies between vertebrates. SARS-CoV-2 and Flu A proteins are acylated by an overlapping set of DHHCs in human cells. We show that these DHHC genes also exist in other virus hosts. Localization of amino acid substitutions in the 3D structure of DHHCs provided no evidence that their activity or substrate specificity is disturbed. We speculate that newly emerged CoVs or Flu viruses also depend on S-acylation for replication and will use the human DHHCs for that purpose. This feature makes these DHHCs attractive targets for pan-antiviral drugs.

Highlights

IntroductionPandemics Caused by Influenza Virus and Coronaviruses
The HA of influenza viruses exhibits the same characteristic (Table S1). This indicates that S-acylation of these cysteines is a very ancient feature acquired early during virus evolution which was fixed in the virus population since it increased viral fitness
This assumption is consistent with experimental data showing that S-acylation of the viral proteins is essential for virus replication in cell culture

Summary

Introduction

Pandemics Caused by Influenza Virus and Coronaviruses. A pandemic is caused by the emergence of a new and highly transmissible virus in immunologically naïve humans. Influenza A viruses leave their animal reservoirs, and jump to either poultry, where they may cause an outbreak of deadly “birdflu”, or to various mammalian species, especially humans and pigs. Pigs are susceptible to both avian and human viruses without prior adaption and, are considered as a “mixing vessel” for the generation of pandemic Flu viruses [4]. Since the bat-associated viruses use different receptors than the other influenza viruses (MHC class II versus sialic acid-containing receptors) [10], their potential for human emergence is currently under investigation

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