title: A polymorphism of the TIM-1 IgV domain: implications for the susceptibility to filovirus infection.
abstract: Filoviruses, including Ebola and Marburg viruses, cause severe hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Human T-cell immunoglobulin and mucin domain 1 (TIM-1) is one of the host proteins that have been shown to promote filovirus entry into cells. In this study, we cloned TIM-1 genes from three different African green monkey kidney cell lines (Vero E6, COS-1, and BSC-1) and found that TIM-1 of Vero E6 had a 23-amino acid deletion and 6 amino acid substitutions compared with those of COS-1 and BSC-1. Interestingly, Vero E6 TIM-1 had a greater ability to promote the infectivity of vesicular stomatitis viruses pseudotyped with filovirus glycoproteins than COS-1-derived TIM-1. We further found that the increased ability of Vero E6 TIM-1 to promote virus infectivity was most likely due to a single amino acid difference between these TIM-1s. These results suggest that a polymorphism of the TIM-1 molecules is one of the factors that influence cell susceptibility to filovirus infection, providing a new insight into the molecular basis for the filovirus host range.
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: Division of Infection and Immunity, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujikura
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Noyori
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kajihara
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Maruyama
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 001-0020, Japan; School of Veterinary Medicine, The University of Zambia, P.O. Box 32379, Lusaka, Zambia. Electronic address: atakada@czc.hokudai.ac.jp.
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D016563:Filoviridae / Q000472:pathogenicity*; D018702:Filoviridae Infections / Q000235:genetics*; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000821:virology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells
chemical_list: D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D049452:Green Fluorescent Proteins
keywords: Entry; Filovirus; Polymorphism; Receptor; Susceptibility; TIM-1