Abstract
Differing sensitivity of influenza A viruses to antiviral effects of the Myxovirus resistance (Mx) protein implies varying global gene expression profiles in the host. The role of Mx protein during lethal avian influenza (AI) virus infection was examined using Mx1-deficient C57BL/6 (B6-Mx1-/-) and congenic Mx1-expressing (B6-Mx1+/+) mice infected with a virulent, mouse-adapted avian H5N2 Ab/Korea/ma81/07 (Av/ma81) virus. After infection, B6-Mx1+/+ mice were completely protected from lethal AI-induced mortality, and exhibited attenuated clinical disease and reduced viral titers and pathology in the lungs, compared with B6-Mx1-/- mice. Transcriptional profiling of lung tissues revealed that most of the genes up-regulated after infection are involved in activation of the immune response and host defense. Notably, more abundant and sustained expression of cytokine/chemokine genes was observed up to 3 dpi in B6-Mx1-/- mice, and this was associated with excessive induction of cytokines and chemokines. Consequently, massive infiltration of macrophages/monocytes and granulocytes into lung resulted in severe viral pneumonia and potentially contributed to decreased survival of B6-Mx1-/- mice. Taken together, our data show that dysregulated gene transcriptional activity corresponded to persistent induction of cytokine/chemokines and recruitment of cytokine-producing cells that promote inflammation in B6-Mx1-/- mouse lungs. Thus, we provide additional evidence of the interplay of genetic, molecular, and cellular correlates governed by the Mx1 protein that critically determine disease outcome during lethal AI virus infection.
| Original language | English |
|---|---|
| Pages (from-to) | 1308-1321 |
| Number of pages | 14 |
| Journal | American Journal of Pathology |
| Volume | 182 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2013 Apr 1 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Early regulation of viral infection reduces inflammation and rescues Mx-positive mice from lethal avian influenza infection. / Song, Min Suk; Cho, Young Hun; Park, Su Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok Il; Lee, Ok Jun; Kong, Byung Whi; Kim, Hyunggee; Shin, Eui Cheol; Kim, Chul Joong; Choi, Young Ki.
In: American Journal of Pathology, Vol. 182, No. 4, 01.04.2013, p. 1308-1321.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Early regulation of viral infection reduces inflammation and rescues Mx-positive mice from lethal avian influenza infection
AU - Song, Min Suk
AU - Cho, Young Hun
AU - Park, Su Jin
AU - Pascua, Philippe Noriel Q
AU - Baek, Yun Hee
AU - Kwon, Hyeok Il
AU - Lee, Ok Jun
AU - Kong, Byung Whi
AU - Kim, Hyunggee
AU - Shin, Eui Cheol
AU - Kim, Chul Joong
AU - Choi, Young Ki
PY - 2013/4/1
Y1 - 2013/4/1
N2 - Differing sensitivity of influenza A viruses to antiviral effects of the Myxovirus resistance (Mx) protein implies varying global gene expression profiles in the host. The role of Mx protein during lethal avian influenza (AI) virus infection was examined using Mx1-deficient C57BL/6 (B6-Mx1-/-) and congenic Mx1-expressing (B6-Mx1+/+) mice infected with a virulent, mouse-adapted avian H5N2 Ab/Korea/ma81/07 (Av/ma81) virus. After infection, B6-Mx1+/+ mice were completely protected from lethal AI-induced mortality, and exhibited attenuated clinical disease and reduced viral titers and pathology in the lungs, compared with B6-Mx1-/- mice. Transcriptional profiling of lung tissues revealed that most of the genes up-regulated after infection are involved in activation of the immune response and host defense. Notably, more abundant and sustained expression of cytokine/chemokine genes was observed up to 3 dpi in B6-Mx1-/- mice, and this was associated with excessive induction of cytokines and chemokines. Consequently, massive infiltration of macrophages/monocytes and granulocytes into lung resulted in severe viral pneumonia and potentially contributed to decreased survival of B6-Mx1-/- mice. Taken together, our data show that dysregulated gene transcriptional activity corresponded to persistent induction of cytokine/chemokines and recruitment of cytokine-producing cells that promote inflammation in B6-Mx1-/- mouse lungs. Thus, we provide additional evidence of the interplay of genetic, molecular, and cellular correlates governed by the Mx1 protein that critically determine disease outcome during lethal AI virus infection.
AB - Differing sensitivity of influenza A viruses to antiviral effects of the Myxovirus resistance (Mx) protein implies varying global gene expression profiles in the host. The role of Mx protein during lethal avian influenza (AI) virus infection was examined using Mx1-deficient C57BL/6 (B6-Mx1-/-) and congenic Mx1-expressing (B6-Mx1+/+) mice infected with a virulent, mouse-adapted avian H5N2 Ab/Korea/ma81/07 (Av/ma81) virus. After infection, B6-Mx1+/+ mice were completely protected from lethal AI-induced mortality, and exhibited attenuated clinical disease and reduced viral titers and pathology in the lungs, compared with B6-Mx1-/- mice. Transcriptional profiling of lung tissues revealed that most of the genes up-regulated after infection are involved in activation of the immune response and host defense. Notably, more abundant and sustained expression of cytokine/chemokine genes was observed up to 3 dpi in B6-Mx1-/- mice, and this was associated with excessive induction of cytokines and chemokines. Consequently, massive infiltration of macrophages/monocytes and granulocytes into lung resulted in severe viral pneumonia and potentially contributed to decreased survival of B6-Mx1-/- mice. Taken together, our data show that dysregulated gene transcriptional activity corresponded to persistent induction of cytokine/chemokines and recruitment of cytokine-producing cells that promote inflammation in B6-Mx1-/- mouse lungs. Thus, we provide additional evidence of the interplay of genetic, molecular, and cellular correlates governed by the Mx1 protein that critically determine disease outcome during lethal AI virus infection.
UR - http://www.scopus.com/inward/record.url?scp=84875200699&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875200699&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2012.12.022
DO - 10.1016/j.ajpath.2012.12.022
M3 - Article
C2 - 23395090
AN - SCOPUS:84875200699
VL - 182
SP - 1308
EP - 1321
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
ER -