Influenza A(H5N1) Virus in Foxes

In 2008, a report was published that mentioned that red foxes (Vulpes vulpes) were potentially at high risk for infection with Influenza A(H5N1) Virus, a highly pathogenic avian influenza[1].

To determine whether these red foxes were susceptible to infection with Influenza A(H5N1) Virus, researchers infected three foxes intratracheally. They excreted virus pharyngeally for 3 to 7 days and had severe pneumonia, myocarditis, and encephalitis.

To see whether foxes can become infected by the presumed natural route, they fed infected bird carcasses to three other red foxes. These foxes excreted virus pharyngeally for 3 to 5 days, but only mild or no pneumonia developed.

This study demonstrated that if red foxes fed on bird carcasses, infected with Influenza A(H5N1) Virus, they can excrete virus while remaining free of severe disease, thereby potentially playing a role in virus dispersal.

Well, that was in 2008 and in a laboratory. What about infections in nature?

During the 2020-2022 epizootic of Influenza A(H5N1) Virus several infections of mammalian species were reported in Europe. In the Netherlands, Influenza A(H5N1) Virus infections were detected in three wild red foxes that were submitted with neurological symptoms between December 2021 and February 2022[2].

Analysis demonstrated the virus was mainly present in the brain, with limited or no detection in the respiratory tract and other organs. Further analysis showed the three fox viruses were not closely related. In addition, limited virus shedding was detected suggesting the virus was not transmitted between the foxes.

Genetic analysis demonstrated the presence of mammalian adaptation E627K in the polymerase basic two (PB2) protein of the two fox viruses. In both foxes the avian (PB2-627E) and the mammalian (PB2-627K) variant were present as a mixture in the virus population, which suggests the mutation emerged in these specific animals.

[Actress Kate Beckinsale with a wild fox: Not a good idea]

Experiments showed mutation PB2-627K increases replication of the virus in mammalian cell lines compared to a chicken cell line, and at the lower temperatures of the mammalian upper respiratory tract. This study showed the Influenza A(H5N1) Virus is capable of adaptation to mammals, however more adaptive mutations are required to allow efficient transmission between mammals.

[1] Reperant et al: Highly Pathogenic Avian Influenza Virus (H5N1) Infection in Red Foxes Fed Infected Bird Carcasses in Emerging Infectious Diseases – 2008. See here.
[2] Bordes et al: Highly pathogenic avian influenza H5N1 virus infections in wild red foxes (Vulpes vulpes) show neurotropism and adaptive virus mutations in BioRxiv – 2022. See here.