Different potential of C-type lectin-mediated entry between Marburg virus strains.
The glycoproteins (GPs) of filoviruses are responsible for virus entry into cells. It is known that GP interacts with cellular C-type lectins for virus attachment to cells. Since primary target cells of filoviruses express C-type lectins, C-type lectin-mediated entry is thought to be a possible determinant of virus tropism and pathogenesis. We compared the efficiency of C-type lectin-mediated entry between Marburg virus strains Angola and Musoke by using a vesicular stomatitis virus (VSV) pseudotype system. VSV pseudotyped with Angola GP (VSV-Angola) infected K562 cells expressing the C-type lectin, human macrophage galactose-type C-type lectin (hMGL), or dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) more efficiently than VSV pseudotyped with Musoke GP (VSV-Musoke). Unexpectedly, the binding affinity of the C-type lectins to the carbohydrates on GPs did not correlate with the different efficiency of C-type lectin-mediated entry. Site-directed mutagenesis identified the amino acid at position 547, which switched the efficiency of C-type lectin-mediated entry. In a three-dimensional model of GP, this amino acid was in close proximity to the putative site of cathepsin processing. Interestingly, the cathepsin inhibitors reduced the infectivity of VSV-Angola less efficiently than that of VSV-Musoke in C-type lectin-expressing K562 cells, whereas only a limited difference was found in control cells. The amino acid at position 547 was critical for the different effects of the inhibitors on the virus infectivities. These results suggest that the efficiency of C-type lectin-mediated entry of filoviruses is controlled not only by binding affinity between C-type lectins and GP but also by mechanisms underlying endosomal entry, such as proteolytic processing by the cathepsins.
Matsuno
Keita
K
Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Kita-20, Nishi-10, Kita-ku, Sapporo 001-0020, Japan.
Kishida
Noriko
N
Usami
Katsuaki
K
Igarashi
Manabu
M
Yoshida
Reiko
R
Nakayama
Eri
E
Shimojima
Masayuki
M
Feldmann
Heinz
H
Irimura
Tatsuro
T
Kawaoka
Yoshihiro
Y
Takada
Ayato
A
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D005822:Genetic Vectors; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D029024:Marburgvirus / Q000502:physiology*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018116:Vesiculovirus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053585:Virus Attachment
C081324:GP-protein, Marburg virus; D037181:Lectins, C-Type; D014759:Viral Envelope Proteins