Comparison of the pathogenic potential of highly pathogenic avian influenza (HPAI) H5N6, and H5N8 viruses isolated in South Korea during the 2016–2017 winter season

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N6) and A(H5N8) virus infections resulted in the culling of more than 37 million poultry in the Republic of Korea during the 2016/17 winter season. Here we characterize two representative viruses, A/Environment/Korea/W541/2016 [Em/W541(H5N6)] and A/Common Teal/Korea/W555/2017 [CT/W555(H5N8)], and evaluate their zoonotic potential in various animal models. Both Em/W541(H5N6) and CT /W555(H5N8) are novel reassortants derived from various gene pools of wild bird viruses present in migratory waterfowl arising from eastern China. Despite strong preferential binding to avian virus–type receptors, the viruses were able to grow in human respiratory tract tissues. Em/W541(H5N6) was found to be highly pathogenic in both chickens and ducks, while CT/W555(H5N8) caused lethal infections in chickens but did not induce remarkable clinical illness in ducks. In mice, both viruses appeared to be moderately pathogenic and displayed limited tissue tropism relative to HPAI H5N1 viruses. Em/W541(H5N6) replicated to moderate levels in the upper respiratory tract of ferrets and was detected in the lungs, brain, spleen, liver, and colon. Unexpectedly, two of three ferrets in direct contact with Em/W541(H5N6)-infected animals shed virus and seroconverted at 14 dpi. CT/W555(H5N8) was less pathogenic than the H5N6 virus in ferrets and no transmission was detected. Given the co-circulation of different, phenotypically distinct, subtypes of HPAI H5Nx viruses for the first time in South Korea, detailed virologic investigations are imperative given the capacity of these viruses to evolve and cause human infections.

A novel European H5N8 influenza A virus has increased virulence in ducks but low zoonotic potential

“…A low infectious dose of 10 2 TCID 50 /animal resulted in a mortality of 60%, while animals receiving higher dosages had to be euthanized before 10 dpi. The final calculated mean lethal dose 50 for the Balb/c mouse experiments was 2.4 × 10 2 /animal, demonstrating clearly a more virulent phenotype than reported previously for H5N8A viruses by others 18 , 54 . Whether this variability reflects different experimental designs e.g., age of the mice, endpoint criteria or represents different molecular determinants of influenza virus pathogenesis in mice will be part of future studies.…”

The Pandemic Threat of Emerging H5 and H7 Avian Influenza Viruses

“…Building upon earlier work on H5 viruses that caused outbreaks in Korea in 2013–2014, two isolates from the 2016–2017 winter season were evaluated for their zoonotic potential [ 103 ]. Specifically, A/environment/Korea/W541/2016 (H5N6) and A/common teal/Korea/W555/2017 (H5N8) were studied as representative H5N6 and H5N8 strains.…”

“…Neither virus transmitted to respiratory contacts, and none of the direct contact animals became infected with A/common teal/Korea/W555/2017 (H5N8); however, three of three direct contact animals shed the A/environment/Korea/W541/2016 (H5N6) virus. Given the propensity for limited transmission, receptor-binding studies were performed and revealed that both viruses had a strong α2,3-SA acid preference, although low-level binding to α2,6-SAs was also observed [ 103 ]. In response to case reports of human infections with H5N6 viruses in China, an additional Korean isolate A/mandarin duck/Korea/K16-187-3/2016 (H5N6) was also evaluated in the ferrets.…”

Avian influenza overview August – November 2018

“…As mentioned in the EFSA report for November 2017 -February 2018 (EFSA et al, 2018c), two novel HPAI A(H5N6) reassortants are cocirculating in Asia:(1) the zoonotic reassortant belonging to clade 2.3.4.4c that was detected in domestic and wild birds in China, Japan, Myanmar, the Philippines, South Korea, Taiwan and Viet Nam, and (2) a reassortant associated with clade 2.3.4.4b that is mainly circulating in Eurasia(Kwon HI et al, 2018;Lee et al, 2018a).New cases of the zoonotic reassortant of HPAI A(H5N6) (2.3.4.4c) were reported from China and Viet Nam between 16 August and 15 November 2018(Figure 11). HPAI A(H5N6) 4.4.2.1.…”

“…an updated nomenclature of clade 2.3.4.4 viruses is pending, the four genetic groups (a, b, c, d) of clade 2.3.4.4 introduced by Lee et al (2018a) are used in this section to give a better insight onto the characteristics of the HPAI A(H5N6) viruses detected in domestic and wild birds.As mentioned in the EFSA report for November 2017 -February 2018(EFSA et al, 2018c), two novel HPAI A(H5N6) reassortants are cocirculating in Asia: (1) the zoonotic reassortant belonging to clade 2.3.4.4c that was detected in domestic and wild birds in China, Japan, Myanmar, the Philippines, South Korea, Taiwan and Viet Nam, and (2) a reassortant associated with clade 2.3.4.4b that is mainly circulating in Eurasia(Kwon HI et al, 2018;Lee et al, 2018a).New cases of the zoonotic reassortant of HPAI A(H5N6) (2.3.4.4c) were reported from China and Viet Nam between 16 August and 15 November 2018 (…”