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ACS Infect Dis. 2016 Jul 8;2(7):471-7. doi: 10.1021/acsinfecdis.6b00064. Epub 2016 Jun 13.

Peptide-Mediated Interference of PB2-eIF4G1 Interaction Inhibits Influenza A Viruses' Replication in Vitro and in Vivo.

Author information

1
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Hong Kong SAR, China.
2
School of Biological Sciences, Faculty of Science, The University of Hong Kong , Hong Kong SAR, China.

Abstract

Influenza viruses are obligate parasites that hijack the host cellular system. Previous results have shown that the influenza virus PB2 subunit confers a dependence of host eukaryotic translation initiation factor 4-γ 1 (eIF4G1) for viral mRNA translation. Here, we demonstrated that peptide-mediated interference of the PB2-eIF4G1 interaction inhibited virus replication in vitro and in vivo. Remarkably, intranasal administration of the peptide provided 100% protection against lethal challenges of influenza A viruses in BALB/c mice, including H1N1, H5N1, and H7N9 influenza virus subtypes. Mapping of the PB2 protein indicated that the eIF4G1 binding sites resided within the PB2 cap-binding domain. Virtual docking analysis suggested that the inhibitory peptide associated with the conserved amino acid residues that were essential to PB2 cap-binding activity. Overall, our results identified the PB2-eIF4G1 interactive site as a druggable target for influenza therapeutics.

KEYWORDS:

PB2; Tat; antiviral peptide; eIF4G1; host−virus interaction; influenza virus

PMID:
27626099
DOI:
10.1021/acsinfecdis.6b00064
[Indexed for MEDLINE]

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