Hepadnaviral replication in HBV-transgenic mice lacking the surface antigen (HBsAg) is controlled by toll-like receptor 3-induced immune responses

2014 ◽  
Vol 52 (08) ◽  
Author(s):  
CI Real ◽  
R Broering ◽  
M Hossbach ◽  
J Deckert ◽  
K Jahn-Hofmann ◽  
...  
2014 ◽  
Vol 21 (12) ◽  
pp. 860-872 ◽  
Author(s):  
M. Jiang ◽  
R. Broering ◽  
M. Trippler ◽  
L. Poggenpohl ◽  
M. Fiedler ◽  
...  

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 940
Author(s):  
Theodor Chitlaru ◽  
Erez Bar-Haim ◽  
Liat Bar-On ◽  
Shahar Rotem ◽  
Hila Cohen ◽  
...  

HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20–30% loss of weight at day 7 and full recovery at days 11–13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses.


2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.


2003 ◽  
Vol 131 (Suppl. 1) ◽  
pp. 11-14 ◽  
Author(s):  
Naohiro Watanabe ◽  
Hidekazu Tamauchi ◽  
Hideyuki Ozawa ◽  
Mamoru Ito ◽  
Zoltan Ovary ◽  
...  

Vaccine ◽  
2001 ◽  
Vol 19 (30) ◽  
pp. 4219-4225 ◽  
Author(s):  
Bo-Jian Zheng ◽  
Mun-Hon Ng ◽  
Li-Fang He ◽  
Xin Yao ◽  
Kwok-Wah Chan ◽  
...  

1997 ◽  
Vol 26 (1) ◽  
pp. 131-137 ◽  
Author(s):  
S.M. Fazle Akbar ◽  
Kazunori Kajino ◽  
Kenji Tanimoto ◽  
Kiyotaka Kurose ◽  
Toshikazu Masumoto ◽  
...  

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