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Single Nucleotide Variants of the Human TIM-1 IgV Domain with Reduced Ability to Promote Viral Entry into Cells
| Title: | Single Nucleotide Variants of the Human TIM-1 IgV Domain with Reduced Ability to Promote Viral Entry into Cells |
| Authors: | Hattori, Takanari Browse this author | | Saito, Takeshi Browse this author | | Miyamoto, Hiroko Browse this author | | Kajihara, Masahiro Browse this author | | Igarashi, Manabu Browse this author | | Takada, Ayato Browse this author →KAKEN DB |
| Keywords: | TIM-1 | | polymorphism | | pseudotyped virus | | glycoprotein | | entry |
| Issue Date: | Oct-2022 |
| Publisher: | MDPI |
| Journal Title: | Viruses-Basel |
| Volume: | 14 |
| Issue: | 10 |
| Start Page: | 2124 |
| Publisher DOI: | 10.3390/v14102124 |
| Abstract: | Human T-cell immunoglobulin mucin 1 (hTIM-1) is known to promote cellular entry of enveloped viruses. Previous studies suggested that the polymorphisms of hTIM-1 affected its function. Here, we analyzed single nucleotide variants (SNVs) of hTIM-1 to determine their ability to promote cellular entry of viruses using pseudotyped vesicular stomatitis Indiana virus (VSIV). We obtained hTIM-1 sequences from a public database (Ensembl genome browser) and identified 35 missense SNVs in 3 loops of the hTIM-1 immunoglobulin variable (IgV) domain, which had been reported to interact with the Ebola virus glycoprotein (GP) and phosphatidylserine (PS) in the viral envelope. HEK293T cells transiently expressing wildtype hTIM-1 or its SNV mutants were infected with VSIVs pseudotyped with filovirus or arenavirus GPs, and their infectivities were compared. Eleven of the thirty-five SNV substitutions reduced the efficiency of hTIM-1-mediated entry of pseudotyped VSIVs. These SNV substitutions were found not only around the PS-binding pocket but also in other regions of the molecule. Taken together, our findings suggest that some SNVs of the hTIM-1 IgV domain have impaired ability to interact with PS and/or viral GPs in the viral envelope, which may affect the hTIM-1 function to promote viral entry into cells. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/87485 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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