TY - JOUR
T1 - A robust mouse model of HPIV-3 infection and efficacy of GS-441524 against virus-induced lung pathology
AU - Lin, Yuxia
AU - Khan, Mona
AU - Weynand, Birgit
AU - Laporte, Manon
AU - Coenjaerts, Frank
AU - Babusis, Darius
AU - Bilello, John P.
AU - Mombaerts, Peter
AU - Jochmans, Dirk
AU - Neyts, Johan
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/9/5
Y1 - 2024/9/5
N2 - Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory tract infections. There are no convenient small-animal infection models. Here, we show viral replication in the upper and lower airways of AG129 mice (double IFNα/β and IFNγ receptor knockout mice) upon intranasal inoculation. By multiplex fluorescence RNAscope and immunohistochemistry followed by confocal microscopy, we demonstrate viral tropism to ciliated cells and club cells of the bronchiolar epithelium. HPIV-3 causes a marked lung pathology. No virus transmission of the virus was observed by cohousing HPIV-3-infected AG129 mice with other mice. Oral treatment with GS-441524, the parent nucleoside of remdesivir, reduced infectious virus titers in the lung, with a relatively normal histology. Intranasal treatment also affords an antiviral effect. Thus, AG129 mice serve as a robust preclinical model for developing therapeutic and prophylactic strategies against HPIV-3. We suggest further investigation of GS-441524 and its prodrug forms to treat HPIV-3 infection in humans.
AB - Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory tract infections. There are no convenient small-animal infection models. Here, we show viral replication in the upper and lower airways of AG129 mice (double IFNα/β and IFNγ receptor knockout mice) upon intranasal inoculation. By multiplex fluorescence RNAscope and immunohistochemistry followed by confocal microscopy, we demonstrate viral tropism to ciliated cells and club cells of the bronchiolar epithelium. HPIV-3 causes a marked lung pathology. No virus transmission of the virus was observed by cohousing HPIV-3-infected AG129 mice with other mice. Oral treatment with GS-441524, the parent nucleoside of remdesivir, reduced infectious virus titers in the lung, with a relatively normal histology. Intranasal treatment also affords an antiviral effect. Thus, AG129 mice serve as a robust preclinical model for developing therapeutic and prophylactic strategies against HPIV-3. We suggest further investigation of GS-441524 and its prodrug forms to treat HPIV-3 infection in humans.
UR - http://www.scopus.com/inward/record.url?scp=85203272747&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-52071-5
DO - 10.1038/s41467-024-52071-5
M3 - Article
C2 - 39237507
AN - SCOPUS:85203272747
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7765
ER -