| First Author | Algaissi A | Year | 2019 |
| Journal | J Infect Dis | Volume | 219 |
| Issue | 5 | Pages | 829-835 |
| PubMed ID | 30256968 | Mgi Jnum | J:286197 |
| Mgi Id | MGI:6402344 | Doi | 10.1093/infdis/jiy574 |
| Citation | Algaissi A, et al. (2019) Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease. J Infect Dis 219(5):829-835 |
| abstractText | 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. |
