Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease. (26th September 2018)

• Record Type: Journal Article
• Authors: Algaissi, Abdullah; Agrawal, Anurodh S; Han, Song; Peng, Bi-Hung; Luo, Chuming; Li, Fang; Chan, Teh-Sheng; Couch, Robert B; Tseng, Chien-Te K
• Is Part Of: Journal of infectious diseases. Volume 219:Number 5(2019)
• Page Start: 829
• Page End: 835
• Publication Date: 2018-09-26
• Subjects: Middle East respiratory syndrome coronavirus -- MERS pathogenesis -- human DPP4 -- transgenic mice -- medical countermeasures for MERS; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy574
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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. Abstract : We demonstrated that elevated levels of circulating soluble human (sh)DPP4 positively correlated with the resistance to MERS-CoV infection and identified the potential of recombinant shDPP4 as a treatment option for MERS.