Abstract
The α-subunit of the eukaryotic initiation factor 2 (eIF-2α) is a key component of the translation machinery of the cell. In response to cellular stress such as viral infections, eIF-2α is phosphorylated by double-stranded RNA-dependent protein kinase (PKR) leading to the inhibition of cellular protein synthesis. The importance of eIF-2α as a regulatory mechanism for protein synthesis is illustrated by the wide variety of strategies employed by viruses to down-regulate PKR. Thus, Vaccinia virus encodes K3L protein, which resembles eIF-2α and acts as a pseudo-substrate inhibitor of PKR. Nucleotide sequencing of the genome of epizootic haematopoietic necrosis virus (EHNV), a member of the genus ranavirus of Iridoviridae, has revealed an eIF-2α equivalent gene. We have cloned and sequenced eIF-2α genes of several iridoviruses of fishes and frogs. The eIF-2α open reading frames and deduced proteins of the iridoviruses investigated exhibit a high degree of homology of both nucleotide and amino acid sequences. At the N-terminus, the iridoviral eIF-2α shows significant homology to the N-termini of cellular initiation factor 2-α of various species, to full-length poxviral eIF-2α proteins, and to the S1 domain of ribosomal proteins. Comparison of amino acid sequences of corresponding iridoviral proteins with eIF-2α homologous proteins of poxviruses and eukaryotes has revealed a high conservation of motifs. A phylogenetic analysis of eukaryotic eIF-2α and poxvirus and iridovirus eIF-2α sequences has demonstrated the relationship of these iridoviruses. In order to investigate the role of the eIF-2α equivalent, respective genes have been expressed in prokaryotic and eukaryotic (insect, fish and chicken cell) systems. The iridoviral eIF-2α protein has a molecular weight of 31 kDa and is cytoplasmic. The cellular and viral protein synthesis of iridoviruses is probably regulated by a mechanism similar to that of Vaccinia virus. Frog-virus 3, the type species of the genus ranavirus of Iridoviridae, has a unique translational efficiency and, moreover, down-regulates the cellular protein synthesis of infected cells.
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Essbauer, S., Bremont, M. & Ahne, W. Comparison of the eIF-2α Homologous Proteins of Seven Ranaviruses (Iridoviridae). Virus Genes 23, 347–359 (2001). https://doi.org/10.1023/A:1012533625571
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DOI: https://doi.org/10.1023/A:1012533625571