tetano
Editor, Senior Moderator
J Gen Virol. 2016 Dec 23. doi: 10.1099/jgv.0.000695. [Epub ahead of print]
[h=1]Effects of PB1-F2 on the pathogenicity of H1N1 swine influenza virus in mice and pigs.[/h] Lee J[SUP]1[/SUP], Henningson J[SUP]2[/SUP], Ma J[SUP]3[/SUP], Duff M[SUP]4[/SUP], Lang Y[SUP]5[/SUP], Li Y[SUP]6[/SUP], Li Y[SUP]7[/SUP], Nagy A[SUP]8[/SUP], Sunwoo S[SUP]9[/SUP], Bawa B[SUP]10[/SUP], Yang J[SUP]11[/SUP], Bai D[SUP]12[/SUP], Richt JA[SUP]13[/SUP], Ma W[SUP]14[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Although several studies have exploited effects of PB1-F2 in swine influenza viruses, its contribution to the pathogenicity of swine influenza viruses remains unclear. Herein, we investigated effects of PB1-F2 on the pathogenicity of influenza virus using a virulent H1N1 A/swine/Kansas/77778/2007 (KS07) virus, which expresses a full-length PB1-F2, in mice and pigs. Using reverse genetics, we generated the wild type KS07 (KS07_WT), a PB1-F2 knockout mutant (KS07_K/O) and its N66S variant (KS07_N66S). KS07_K/O showed similar pathogenicity in mice as the KS07_WT, whereas KS07_N66S displayed enhanced virulence when compared to the other two viruses. KS07_WT exhibited more efficient replication in lungs and nasal shedding in infected pigs than the other two viruses. Pigs infected with the KS07_WT had higher pulmonary levels of GM-CSF, IFN-γ, IL-6 and IL-8 at 3 and 5 days post-infection, as well as lower levels of IL-2, IL-4 and IL-12 at 1 day post-infection compared to those infected with the KS07_K/O. These results indicate that PB1-F2 modulates KS07 H1N1 virus replication, pathogenicity and innate immune responses in pigs, and the single substitution at position 66 (N/S) in the PB1-F2 plays a critical role in virulence in mice. Taken together, our results provide new insights into the effects of PB1-F2 on the virulence of influenza virus in swine, and support PB1-F2 as a virulence factor of influenza A virus in a strain- and host-dependent manner.
PMID: 28008819 DOI: 10.1099/jgv.0.000695
[PubMed - as supplied by publisher]
[h=1]Effects of PB1-F2 on the pathogenicity of H1N1 swine influenza virus in mice and pigs.[/h] Lee J[SUP]1[/SUP], Henningson J[SUP]2[/SUP], Ma J[SUP]3[/SUP], Duff M[SUP]4[/SUP], Lang Y[SUP]5[/SUP], Li Y[SUP]6[/SUP], Li Y[SUP]7[/SUP], Nagy A[SUP]8[/SUP], Sunwoo S[SUP]9[/SUP], Bawa B[SUP]10[/SUP], Yang J[SUP]11[/SUP], Bai D[SUP]12[/SUP], Richt JA[SUP]13[/SUP], Ma W[SUP]14[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Although several studies have exploited effects of PB1-F2 in swine influenza viruses, its contribution to the pathogenicity of swine influenza viruses remains unclear. Herein, we investigated effects of PB1-F2 on the pathogenicity of influenza virus using a virulent H1N1 A/swine/Kansas/77778/2007 (KS07) virus, which expresses a full-length PB1-F2, in mice and pigs. Using reverse genetics, we generated the wild type KS07 (KS07_WT), a PB1-F2 knockout mutant (KS07_K/O) and its N66S variant (KS07_N66S). KS07_K/O showed similar pathogenicity in mice as the KS07_WT, whereas KS07_N66S displayed enhanced virulence when compared to the other two viruses. KS07_WT exhibited more efficient replication in lungs and nasal shedding in infected pigs than the other two viruses. Pigs infected with the KS07_WT had higher pulmonary levels of GM-CSF, IFN-γ, IL-6 and IL-8 at 3 and 5 days post-infection, as well as lower levels of IL-2, IL-4 and IL-12 at 1 day post-infection compared to those infected with the KS07_K/O. These results indicate that PB1-F2 modulates KS07 H1N1 virus replication, pathogenicity and innate immune responses in pigs, and the single substitution at position 66 (N/S) in the PB1-F2 plays a critical role in virulence in mice. Taken together, our results provide new insights into the effects of PB1-F2 on the virulence of influenza virus in swine, and support PB1-F2 as a virulence factor of influenza A virus in a strain- and host-dependent manner.
PMID: 28008819 DOI: 10.1099/jgv.0.000695
[PubMed - as supplied by publisher]