Cell-penetrating peptide-mediated cell entry of H5N1 highly pathogenic avian influenza virus.

Abstract

H5N1 highly pathogenic avian influenza virus (HPAIV) poses a huge threat to public health and the global economy. These viruses cause systemic infection in poultry and accidental human infection leads to severe pneumonia, associated with high mortality rates. The hemagglutinin (HA) of H5N1 HPAIV possesses multiple basic amino acids, as in the sequence RERRRKKR at the cleavage site; however, the role of this motif is not fully understood. Here, we showed that a 33-amino acid long peptide derived from HA of H5N1 HPAIV (HA314-46) has the potential to penetrate various cells and lung tissue through a sialic acid-independent endocytotic pathway. Mutant peptide analyses revealed that the cysteine residue at position 318 and multiple basic amino acids were essential for the cell-penetrating activity. Moreover, reassortant viruses possessing H5 HA could enter sialic acid-deficient cells, and virus internalisation was facilitated by cleavage with recombinant furin. Thus, our findings demonstrate that the HA314-46 motif exhibits cell-penetrating activity through a sialic acid-independent cell entry mechanism.

• Authors: Naoki Kajiwara, Namiko Nomura, Masako Ukaji, Naoki Yamamoto, Michinori Kohara, Fumihiko Yasui, Yoshihiro Sakoda, Hiroshi Kida, Futoshi Shibasaki
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 18008 (10 22 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 33093460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell-Penetrating Peptides
• Hemagglutinin Glycoproteins, Influenza Virus
• hemagglutinin, avian influenza A virus

Topics

• Animals
• CHO Cells
• Cell-Penetrating Peptides (administration & dosage)
• Cricetulus
• Hemagglutinin Glycoproteins, Influenza Virus (metabolism)
• Influenza A Virus, H5N1 Subtype (pathogenicity)
• Mice
• Orthomyxoviridae Infections (drug therapy, virology)
• Virus Internalization (drug effects)