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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/1401
Elevated human dipeptidyl peptidase 4 expression reduces the susceptibility of hDPP4 transgenic mice to middle east respiratory syndrome coronavirus infection and disease | |
Algaissi, A Agrawal, A Han, S Peng, B Luo, C Li, F Chan, T Couch, R Tseng, C | |
Acceso Abierto | |
Atribución-NoComercial-SinDerivadas | |
BACKGROUND: The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) infections pose threats to public health worldwide, making an understanding of MERS pathogenesis and development of effective medical countermeasures (MCMs) urgent.METHODS: We used homozygous (+/+) and heterozygous (+/-) human dipeptidyl peptidase 4 (hDPP4) transgenic mice to study the effect of hDPP4 on MERS-CoV infection. Specifically, we determined values of 50% lethal dose (LD50) of MERS-CoV for the 2 strains of mice, compared and correlated their levels of soluble (s)hDPP4 expression to susceptibility, and explored recombinant (r)shDPP4 as an effective MCM for MERS infection.RESULTS: hDPP4+/+ mice were unexpectedly more resistant than hDPP4+/- mice to MERS-CoV infection, as judged by increased LD50, reduced lung viral infection, attenuated morbidity and mortality, and reduced histopathology. Additionally, the resistance to MERS-CoV infection directly correlated with increased serum shDPP4 and serum virus neutralizing activity. Finally, administration of rshDPP4 led to reduced lung virus titer and histopathology.CONCLUSIONS: Our studies suggest that the serum shDPP4 levels play a role in MERS pathogenesis and demonstrate a potential of rshDPP4 as a treatment option for MERS. Additionally, it offers a validated pair of Tg mice strains for characterizing the effect of shDPP4 on MERS pathogenesis. | |
The Journal of Infectious Diseases | |
2019 | |
Preimpreso | |
https://coronavirus.1science.com/item/2ba7aa8d1dc8a34da5e67c83b77eaa5aace622d1 | |
Inglés | |
VIRUS RESPIRATORIOS | |
Aparece en las colecciones: | Artículos científicos |
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