We need to keep an eye on avian influenza

H5N1 avian influenza viruses of the A/goose/Guangdong/1/96 lineage have been circulating in wild birds for many years, have inflicted significant economic losses on the poultry industry and have caused zoonotic infections since 1997. However, the recent spread of avian H5N1 virus to the Americas and its detection in mammals have raised concerns about its pandemic potential.

Avian influenza viruses are typically relatively harmless for humans. Even in birds, infections are often mild or asymptomatic. However, these viruses can become of greater concern under certain circumstances. One problematic scenario is when avian influenza viruses become highly pathogenic for poultry. This typically happens when the haemagglutinin (HA), one of the two proteins on the surface of the virus (with neuraminidase (NA) being the second protein), acquires a polybasic cleavage site. This allows the HA to be activated not just by select proteases, which restricts the virus to certain tissues, but by furin-like proteases found in most tissues, allowing wider dissemination of the virus throughout the host. This polybasic cleavage site is the same element that is found in some coronaviruses, including SARS-CoV-2 and some human seasonal coronaviruses. Acquisition of a polybasic cleavage site can happen spontaneously, often when an avian influenza virus enters a poultry farm and replicates extensively in large concentrations of susceptible animals. Extensive replication increases the chance of insertions occurring in the viral genome, which can lead to the emergence of a polybasic cleavage site. In some cases, the source material of the insertion seems to be fragments of chicken ribosomal RNA1. This acquisition of a polybasic cleavage site by avian influenza viruses has been well documented in poultry farms across the United States; for example, it has occurred twice in the past few years, with an H7N8 virus in Indiana in 2016 (ref. 2) and with an H7N9 virus in Tennessee in 2017 (ref. 3). It has also been documented for H5 subtype HA. Avian H5 and H7 subtype influenza viruses with polybasic cleavage sites cause severe disease in poultry, result in economic losses including increased poultry and egg prices, and endanger wild birds. These viruses can also cause severe disease in humans if large amounts are inhaled deep into the lungs. When that occurs, the fatality rates can be high. However, these avian influenza viruses are not efficient in infecting humans or other mammals, do not replicate well in the human upper respiratory tract and, therefore, usually do not spread from human to human. Typically, they are problematic for individuals in direct contact with infected birds but they are unlikely to cause larger human outbreaks.