Transmission experiments support clade-level differences in the transmission and pathogenicity of Cambodian influenza A/H5N1 viruses

Abstract

Influenza A/H5N1 has circulated in Asia since 2003 and is now enzootic in many countries in that region. In Cambodia, the virus has circulated since 2004 and has intermittently infected humans. During this period, we have noted differences in the rate of infections in humans, potentially associated with the circulation of different viral clades. In particular, a reassortant clade 1.1.2 virus emerged in early 2013 and was associated with a dramatic increase in infections of humans (34 cases) until it was replaced by a clade 2.3.2.1c virus in early 2014. In contrast, only one infection of a human has been reported in the 6 years since the clade 2.3.2.1c virus became the dominant circulating virus. We selected three viruses to represent the main viral clades that have circulated in Cambodia (clade 1.1.2, clade 1.1.2 reassortant, and clade 2.3.2.1c), and we conducted experiments to assess the virulence and transmissibility of these viruses in avian (chicken, duck) and mammalian (ferret) models. Our results suggest that the clade 2.3.2.1c virus is more "avian-like," with high virulence in both ducks and chickens, but there is no evidence of aerosol transmission of the virus from ducks to ferrets. In contrast, the two clade 1 viruses were less virulent in experimentally infected and contact ducks. However, evidence of chicken-to-ferret aerosol transmission was observed for both clade 1 viruses. The transmission experiments provide insights into clade-level differences that might explain the variation in A/H5N1 infections of humans observed in Cambodia and other settings.

Differences in Highly Pathogenic H5N6 Avian Influenza Viral Pathogenicity and Inflammatory Response in Chickens and Ducks

“…Infection with HPAIVs, such as H5N1, H5N6, and H5N8, in waterfowls is often asymptomatic, but in chickens and in humans, it can induce severe disease symptoms and death (Bean et al, 2013;Burggraaf et al, 2014;Kwon et al, 2018b;Uchida et al, 2019). However, some recent H5Nx subtype viruses caused unusually high mortality in ducks (Sturm-Ramirez et al, 2004;Li et al, 2017a;Kwon et al, 2018a;Leyson et al, 2019;Horwood et al, 2020). Comparative analyses between natural hosts (e.g., ducks) and spillover hosts (e.g., chickens) and understanding the mechanisms by which some H5Nx viruses cause death in ducks will help to identify the key processes in influenza susceptibility and pathogenesis.…”

Emerging of H5N6 Subtype Influenza Virus with 129-Glycosylation Site on Hemagglutinin in Poultry in China Acquires Immune Pressure Adaption

“…Four hours postinoculation, five uninfected SPF chickens were placed together with the infected chickens. Mortality was monitored for 2 weeks, cloaca and oropharyngeal swabs of the directly exposed group were collected to determine virus shedding, and all swabs were inoculated with chicken embryos ( 40 ). Three additional infected chickens from each group were housed in other isolators and euthanized 3 days postinfection (dpi).…”

Avian influenza H5N1: still a pandemic threat?

“…Over the ~25 years since A/H5N1 first emerged, the virus has diversified into multiple HA clades and subclades. Some of these strains have displayed greater fitness for spreading amongst poultry and others have been associated with a higher risk of human infection and disease 24,25 .…”

“…Viral surveillance in LBMs has established that H5N1 circulation is occurring at levels similar to those detected during the peak period of human infections [8][9][10][11][12] . The current lack of human H5N1 cases may be linked to the dominant strain currently circulating (clade 2.3.2.1) being more 'avian-like' and not as readily able to jump the species gap to infect humans 25 . However, in some countries, H5N6 reassortant viruses have replaced H5N1 as the dominant virus in circulation, thus highlighting the threat for the emergence of novel AIV viruses 33 .…”