Newly Isolated H16N3 Avian Influenza Viruses Show Future Zoonotic Potential

In the wake of SARS-CoV-2 likely transmitting from an animal source to humans prior to the onset of a global pandemic, the need for close monitoring of emerging viruses with the potential for future zoonosis has never been more necessary.

Avian influenza virus subtype H16N3 was first isolated in 1975, and can now be found around the world. The H16 subtype avian influenza virus was first identified in 2005, and the greatest prevalence is found in the Netherlands and Norway. The exact zoonotic potential of the avian viral strain, however, remains poorly understood.

The investigators of a new study published in Transboundary and Emerging Diseases conducted avian influenza surveillance in wild bird gatherings in western China between 2017 through 2019, isolating and exploring the biological characteristics of 2 different H16N3 subtype influenza viruses.

The study team conducted sample collections, viral identification, genome sequencing, phylogenetic analysis, and investigations of receptor-binding preferences.

In October 2018, 248 fecal samples were collected from wild birds in the Shahu Wetland in Ningxia Hui Autonomous Region. After laboratory transport, viral isolation was performed and 2 H16N3 viruses were identified. With detection in 2 of 248 samples, the avian influenza virus isolation rate was 0.8%.

These are the first H16N3 subtype influenza A viruses isolated in western China. Isolates were named A/great black‐headed gull/Ningxia/1/2018(H16N3) and A/great black‐headed gull/Ningxia/2/2018(H16N3).

Whole genomes were sequenced and uploaded to the Global Initiative on Sharing All Influenza Data EpiFlu database.

Homology analysis revealed the hemagglutination genes of the 2 H16N3 viruses had the most homology with A/black‐headed gull/Netherlands/37/2011(H16N3), indicating Eurasian rather than North American lineage.

Neuraminidase genes were likely derived from duck viruses.

“Interestingly, the PB1 gene of the great black‐headed gull/Ningxia/1/2018(H16N3) virus was from A/duck/Hubei/ZYSYG3/2015(H6N2) and is a ternary recombinant virus from gull‐, swan‐ and duck‐originated viruses,” the study authors observed.

The investigators were able to estimate that the reassortment events producing the 2 viral subtypes occurred between July 2010 and September 2016.

The viruses both bound to human and avian-type receptors, with great black‐headed gull/Ningxia/1/2018(H16N3) preferentially binding to a human-type receptor and great black‐headed gull/Ningxia/2/2018(H16N3) binding preferentially to an avian-type receptor.

“The change in receptor‐binding preference from α‐2,3‐linked sialic acids (avian‐type receptors) to α‐2,6‐linked sialic acids (human‐type receptors) is believed to be a prerequisite for an avian influenza virus to be transmitted between humans,” the study authors wrote.

Due to the preferential binding of great black‐headed gull/Ningxia/1/2018(H16N3) to human receptors, the type was considered the more likely to present a future health threat to humans.

While a lack of pathogenicity in mouse models and mammalian cell‐restricted growth seems to show these viruses are less harmful in mammals than many other viruses at present, phylogenetic analysis indicating inter‐species genetic reassortment suggests the potential for change.

Also concerning were the receptor preference findings, leading the authors to recommend increased surveillance of the emergence and spread of avian influenza virus subtype H16N3 in wild birds.