Dutch H5N8 Highly Pathogenic Avian Influenza virus does not cause severe disease in ferrets, nor is it easily transmissible between ferrets

NIAID CEIRS | Research Publication Commentary

Richard, M et al. Low Virulence and Lack of Airborne Transmission of the Dutch Highly Pathogenic Avian Influenza Virus H5N8 in Ferrets. PLoS One. 2015 June 19.

Highly pathogenic avian influenza (HPAI) viruses are lethal to wild birds and poultry, causing large-scale outbreaks among poultry flocks in Europe, Asia, the United States, and Canada. Human infections of HPAI are rare, but cases are associated with severe disease and death. The HPAI H5N8 subtype was first detected in domestic poultry in China in 2010 and reemerged early in 2014 in poultry in South Korea and Japan. By late 2014, HPAI H5N8 viruses had spread to Europe and North America.

The hemagglutinin (HA) gene segment of the circulating HPAI H5N8 viruses originated from another HPAI strain, A/Goose/Guangdong/1/1996 (H5N1). H5N1 viruses related to A/goose/Guangdong infected humans in 1997 and has reappeared to cause human infections every year since 2003 with about 50% lethality, raising concerns that the new H5N8 strains may also pose a threat to humans. Previous studies have shown that the HPAI H5N8 virus isolated in South Korea exhibited low virulence and low transmissibility in ferrets, which are used as a model for the ability to infect humans. However, sequence comparison revealed that European HPAI H5N8 viruses differ from their Asian counterparts by several amino acids across multiple gene segments. Drs. Mathilde Richard and Sander Herfst set out to test the virulence and transmissibility of the European HPAI H5N8 virus in ferrets.

Ferrets inoculated with the HPAI H5N8 virus A/Chicken/Netherlands/EMC-3/2014 did not develop a severe infection and displayed only mild symptoms of disease. Following infection, virus levels from throat and nasal swabs decreased rapidly, indicating poor virus shedding. The research team also investigated the ability of the virus to spread through the air. Four ferrets inoculated with the virus were placed, in separate cages, opposite healthy uninfected ferrets for a seven day period to model aerosol transmission. Even after exposure to the infected ferrets, the healthy ferrets did not display symptoms of disease, had no replicating virus in their respiratory tissues, and did not develop antibodies against the virus, indicating they were not infected.

Richard, Herfst, and colleagues demonstrate that the HPAI H5N8 virus replicates poorly in ferrets with low virulence and is not capable of airborne transmission. This work indicates that the novel amino acid substitutions identified in the European HPAI H5N8 strains are not associated with increased pathogenesis or transmissibility. The lack of severe disease and transmission in a mammalian model suggests that the public health risk of a human outbreak caused by the European HPAI H5N8 strain is low. However, given the mutation and reassortment potential of influenza viruses, it is essential that H5N8 and other HPAI strains continue to be monitored and studied.