Human Immunity and Susceptibility to Influenza A(H3) Viruses of Avian, Equine, and Swine Origin

Abstract

I nfluenza A viruses (IAVs) of the H3 subtype are endemic to humans, swine, and wild birds; they also cause outbreaks in horses and are often detected in domestic birds. An H3 IAV that crosses the species barrier from animals to humans can result in a pandemic if the virus carries a hemagglutinin (HA) against which humans lack protective antibodies and the virus readily replicates in and spreads among humans. For example, in 1968, transmission of an IAV with an avian-origin H3 HA to humans caused the influenza A(H3N2) pandemic (1).The natural IAV reservoir is considered to be wild waterfowl, but transmission to domestic poultry is frequent. Avian H3 IAVs are classified as Eurasian and North American lineages, although the HA of these viruses is antigenically closely related (2,3). In contrast, after being introduced to humans in 1968, the HA of human H3 IAVs quickly drifted away from that of the avian precursor IAV. Consequently, contemporary human H3 IAVs are antigenically divergent from those in birds (2). Similarly, avian H3 IAVs were introduced into horses in the 1960s, after which their HA antigenically drifted. That evolution was, however, different and slower than for human H3 IAVs (4). Equine H3 IAVs of Florida clade 1 (FC1) are currently predominant (5). All swine H3 IAVs derived their HA from human IAVs.H3 IAVs from swine in Europe originated from a human IAV that circulated in the late 1970s. Of the 2 major lineages cocirculating in North America, cluster IV-A was derived from human IAVs from the late 1990s and novel human-like swine H3 IAVs from human IAVs from the early 2010s (6). H3 IAVs undergo slower antigenic drift in swine than in humans. Consequently, persons born after the swine viruses' human ancestor IAV had circulated are unlikely to have cross-reactive antibodies against the swine H3 IAVs. Therefore, with time, human population immunity against swine H3 IAVs decreases, increasing the pandemic risk (7-10).The infectious potential of swine H3 IAVs for humans is evident from >400 recorded zoonotic infections in the United States caused by North American cluster IV-A or novel human-like H3 swine IAVs. Four zoonotic infections with H3 IAVs from swine in Europe have also been reported (6,(11)(12)(13). H3 IAVs from equids can infect humans under experimental conditions, but there are no confirmed cases of natural transmission (14). Animal H3 IAVs might, however, become more adapted to humans by accumulating mutations in their viral proteins, reassortment of gene segments with IAVs of different species, or both (6,15). Avian H3 IAVs can infect humans directly or via an intermediate host, such as poultry or swine (2,15). In 2019, an H3N1 IAV that

Long-term co-circulation of multiple influenza A viruses in pigs, Guangxi, China

“…In addition, the pdm/09-like internal gene cassette was successfully incorporated into the swine H3N2 virus, and it has carried the surface genes from the recent human-like H3N2 (HL H3N2) lineage since 2010 [ 10 , 13 , 14 ]. Importantly, the swine H3 IAVs were found to have been derived from human-like viruses, which had a higher potential to infect humans because they could preferentially bind to the human-type α−2,6 sialic acid receptors [ 15 ]. Of note, the pdm/09 internal gene cassette gradually evolved and may act as the TR internal gene (TRIG) cassette to accommodate the surface genes from different origins.…”