A Comparative Study of Short Linear Motif Compositions of the Influenza A Virus Ribonucleoproteins

Abstract

Protein-protein interactions through short linear motifs (SLiMs) are an emerging concept that is different from interactions between globular domains. The SLiMs encode a functional interaction interface in a short (three to ten residues) poorly conserved sequence. This characteristic makes them much more likely to arise/disappear spontaneously via mutations, and they may be more evolutionarily labile than globular domains. The diversity of SLiM composition may provide functional diversity for a viral protein from different viral strains. This study is designed to determine the different SLiM compositions of ribonucleoproteins (RNPs) from influenza A viruses (IAVs) from different hosts and with different levels of virulence.The 96 consensus sequences (regular expressions) of SLiMs from the ELM server were used to conduct a comprehensive analysis of the 52,513 IAV RNP sequences. The SLiM compositions of RNPs from IAVs from different hosts and with different levels of virulence were compared. The SLiM compositions of 845 RNPs from highly virulent/pandemic IAVs were also analyzed. In total, 292 highly conserved SLiMs were found in RNPs regardless of the IAV host range. These SLiMs may be basic motifs that are essential for the normal functions of RNPs. Moreover, several SLiMs that are rare in seasonal IAV RNPs but are present in RNPs from highly virulent/pandemic IAVs were identified.The SLiMs identified in this study provide a useful resource for experimental virologists to study the interactions between IAV RNPs and host intracellular proteins. Moreover, the SLiM compositions of IAV RNPs also provide insights into signal transduction pathways and protein interaction networks with which IAV RNPs might be involved. Information about SLiMs might be useful for the development of anti-IAV drugs.

Proteome-wide analysis of human motif-domain interactions mapped on influenza A virus

“…This observation suggests that functional motifs are more stable in the proteins involved in the transcriptional machinery of the IAV. On the other hand, the fact that the number of motifs with an occurrence of less than 70% is higher than the motifs with an occurrence above of 70%, suggests that those rarely motifs could be arising by mutations and are present in specific IAV strains as previously indicated [ 22 ]. Most of those motifs mapped an amino acid sequence that were absent or occurred very rarely (particularly those MDIs of 3 to 4 amino acid of length) in the shuffled datasets indicating that they are functional motifs.…”

The analysis on the human protein domain targets and host-like interacting motifs for the MERS-CoV and SARS-CoV/CoV-2 infers the molecular mimicry of coronavirus

“…The ORF1ab contains the nonstructural proteins responsible for the translation machinery of viruses in the intracellular environment [ 42 ] and the S protein is essential for the virus’s attachment to the host cell [ 43 ]. The tendency of motifs to appear on the proteins involved in virus replication was also observed in influenza viruses [ 44 ]. Thus, the high frequency of host-like motifs in those viral proteins suggests that such proteins could be the master kidnappers.…”

Convergent evolution and mimicry of protein linear motifs in host–pathogen interactions

“…Linear motif repertoire has been linked to changes in viral phenotypic traits such as virulence [65][66][67], persistence [68,69,70 ] tropism [62 ], oncogenicity [26,71,72], and response to therapy [73]. The association may be inferred from purely statistical correlation between motif repertoire and phenotypic traits [62 ,67,68,73], such as the correspondence between the motif repertoire in the HIV proteome and response of patients to antiretroviral therapy [73].…”