Abstract Title
Pathobiology and replication of zoonotic H7N7 avian influenza virus in poultry, mammals and ex-vivo models
Abstract
In 2003, a HPAIV H7N7 outbreak in the Netherlands, Germany and Belgium resulted in the death of ~30 million birds and 89 confirmed human infections. A polybasic cleavage site (pCS) in the hemagglutinin (HA) protein is one of the main virulence determinants in HPAIV in chickens but less is known about the role of the viral polymerase segments in the transition of LP to HPAIV in chickens. Likewise, little is known about the role of pCS for adaptation of AIV in mammals.
Here, recombinant LP H7N7 viruses carrying a pCS (LP_pCS) with or without the polymerase segments from German HPAIV H7N7 were constructed and characterized. Chickens and mice were infected with recombinant viruses to assess virus virulence, and replication. In addition, ex-vivo infected precision cut lung slices (PCLS) from mice were established as an alternate infection model and compared to DISCO cleared in vivo infected mice lungs.
In chickens, we found that the pCS increased the virulence of LP H7N7, close to the level of HP H7N7, whereas the introduction of the HP H7N7 polymerase segments reduced the virulence of recombinant viruses compared to LP_pCS. Interestingly neither the pCS nor the polymerase segments affected virulence of this H7N7 in mice or the viral distribution in ex-vivo PCLS.
These results indicate that virulence determinants of HPAIV H7N7 in mammals differ from those in poultry and highlight the feasibility of PCLS and Light Sheet Microscopy-Assisted 3D Analysis for studying the adaptation of HPAIV in mammals.
Here, recombinant LP H7N7 viruses carrying a pCS (LP_pCS) with or without the polymerase segments from German HPAIV H7N7 were constructed and characterized. Chickens and mice were infected with recombinant viruses to assess virus virulence, and replication. In addition, ex-vivo infected precision cut lung slices (PCLS) from mice were established as an alternate infection model and compared to DISCO cleared in vivo infected mice lungs.
In chickens, we found that the pCS increased the virulence of LP H7N7, close to the level of HP H7N7, whereas the introduction of the HP H7N7 polymerase segments reduced the virulence of recombinant viruses compared to LP_pCS. Interestingly neither the pCS nor the polymerase segments affected virulence of this H7N7 in mice or the viral distribution in ex-vivo PCLS.
These results indicate that virulence determinants of HPAIV H7N7 in mammals differ from those in poultry and highlight the feasibility of PCLS and Light Sheet Microscopy-Assisted 3D Analysis for studying the adaptation of HPAIV in mammals.
Co-Author(s)
Diana I. Palme1, Henriette Schwotzer1, David Scheibner1,2, Maryna Kuryshko1, Christine Luttermann3, Thomas C. Mettenleiter4, Dmitry Ushakov1, Stefan Finke1 and Elsayed M. Abdelwhab1
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health