Genetic Determinants for Adaptation and Virulence of Avian Influenza Viruses in Birds and Mammals

von Dr. El-Sayed M. Abdel-Whab

448 Seiten, Hardcover

Kurzbeschreibung des Verlags

Avian influenza viruses (AIV) infect a wide range of birds and mammals causing asymptomatic to fatal infections. They cause severe economic losses in the poultry industry, and threaten public health. One of the most powerful tools for the evolution of AIV is its segmented RNA genome, which is composed of eight gene segments. These gene segments can be changed or exchanged due to errors (i.e. mutations) of the viral polymerase during replication or upon coinfection of cells with different AIV strains (i.e. reassortment), respectively. Mutations of AIV evolve rapidly under selective pressure exerted by the application of antivirals (e.g. amantadine) and vaccines or jumping from species to species. The development of genetic manipulation tools, such as reverse genetics, made it possible to insert specific mutations or to rearrange gene segments of two different AIV strains and characterize the resulting phenotypes. We used reverse genetics to study the genetic determinants for efficient replication of AIV in amantadine¬treated or vaccinated poultry, the transition of low pathogenicity (LP) AIV to high pathogenicity (HP) AIV in different bird species, and mutations linked to the transmission of AIV from poultry to seals and humans. Under antiviral or vaccination pressure, AIV acquired 1 and 4 mutations in the matrix-2 (M2) and hemagglutinin (HA) proteins, respectively which increased virus fitness in poultry. Similarly, we showed that the genetic determinants for the transition of some LPAIV to HPAIV are virus- and host-specific. While some AIV required a few mutations in the HA to exhibit high virulence in chickens, other AIV required mutations in almost all gene segments. Interestingly, virulence determinants and host responses in turkeys and ducks were completely different compared to chickens. After bird-to-seal transmission, AIV acquired mutations in the HA receptor binding domain, which conferred high affinity to mammal-type receptors. Increased replication of different AIV in human cells and mammal models was associated with mutations in the neuraminidase (NA), which is responsible for virus release from infected cells, and non-structural protein 1 (NS1), which is the main AIV protein to antagonize the host innate immune response. Our results reflect the high plasticity of the influenza virus genome and the ability to adapt to different birds and mammals by different mechanisms. These studies are helpful to control AIV in poultry and to predict viruses with considerable potential to infect mammals including humans.

• Reihe: Edition Scientifique
• ISBN: 9783835972513
• Sprache: Englisch
• Erscheinungsdatum: 29.07.2025
• Genre: Medizin/Veterinärmedizin
• Verlag: VVB Laufersweiler Verlag