TY - JOUR
T1 - Bovine lactoferrin prevents influenza a virus infection by interfering with the fusogenic function of viral hemagglutinin
AU - Superti, Fabiana
AU - Agamennone, Mariangela
AU - Pietrantoni, Agostina
AU - Ammendolia, Maria Grazia
PY - 2019/1
Y1 - 2019/1
N2 - Bovine lactoferrin (bLf) is an iron-binding glycoprotein folded in two symmetric globular lobes (N-and C-lobes) with potent antimicrobial and immunomodulatory activities. Recently, we have shown that bLf, and in particular its C-lobe, interacts with influenza A virus hemagglutinin and prevents infection by different H1 and H3 viral subtypes. Influenza virus hemagglutinin (HA), and in particular its highly conserved fusion peptide involved in the low-pH-mediated fusion process, plays a significant role in the early steps of viral infection and represents an attractive target for the development of anti-influenza drugs. In the present research, we further investigated the influence of low pH on the interactions between bLf and influenza A H1N1 virus by different techniques, such as enzyme-linked immunosorbent assay, electron microscopy, hemolysis inhibition assay, and time course assay. Our results demonstrate that lactoferrin interaction with influenza hemagglutinin at low pH induces alterations that stabilize the conformation of the hemagglutinin, resulting in the inhibition of the fusion peptide activity. Taken together, our data allowed to better characterize the HA-specific inhibiting activity of bLf and to confirm HA as a good target for drug development.
AB - Bovine lactoferrin (bLf) is an iron-binding glycoprotein folded in two symmetric globular lobes (N-and C-lobes) with potent antimicrobial and immunomodulatory activities. Recently, we have shown that bLf, and in particular its C-lobe, interacts with influenza A virus hemagglutinin and prevents infection by different H1 and H3 viral subtypes. Influenza virus hemagglutinin (HA), and in particular its highly conserved fusion peptide involved in the low-pH-mediated fusion process, plays a significant role in the early steps of viral infection and represents an attractive target for the development of anti-influenza drugs. In the present research, we further investigated the influence of low pH on the interactions between bLf and influenza A H1N1 virus by different techniques, such as enzyme-linked immunosorbent assay, electron microscopy, hemolysis inhibition assay, and time course assay. Our results demonstrate that lactoferrin interaction with influenza hemagglutinin at low pH induces alterations that stabilize the conformation of the hemagglutinin, resulting in the inhibition of the fusion peptide activity. Taken together, our data allowed to better characterize the HA-specific inhibiting activity of bLf and to confirm HA as a good target for drug development.
KW - Antiviral agents
KW - Fusion peptide
KW - Influenza virus
KW - Lactoferrin
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U2 - 10.3390/v11010051
DO - 10.3390/v11010051
M3 - Article
C2 - 30641890
AN - SCOPUS:85060023226
VL - 11
JO - Viruses
JF - Viruses
SN - 1999-4915
IS - 1
M1 - 51
ER -