Swine influenza virus : evolution, epidemiology and risk assessment

Abstract

Zoonotic influenza infections continue to be a threat to human health and have caused multiple epidemics in the past few decades. Pig is in particular important as an intermediate host of influenza viruses since they are susceptible to influenza viruses from various species and contribute to viral genetic evolution that facilitates cross-species transmission as demonstrated in the emergence of 2009 H1N1 pandemic. Robust swine influenza surveillance and risk assessment are essential to understand the viral epidemiology in domestic pigs and help assess the potential risk of spillover to humans for developing better pandemic preparedness and risk-reduction.

China and Vietnam are the two main pig consuming countries in Asia. We carried out slaughterhouse surveillance in pigs in Hong Kong and Hanoi, Vietnam. Since that abattoir in Hong Kong receives pigs from over 10 providences in mainland China, it provides a window on virus diversity in China. I analyzed serological and virological data from surveillance in the Hong Kong swine abattoir carried out from 2012-2016, to provide evidence that the transportation system of imported live pigs provides a greater force of infection compared to that at farm environment. Molecular epidemiology highlighted the occurrence of cross transmission between swine influenza viruses during the transportation to Hong Kong.

Whole genome sequence analysis for the 115 swine influenza viruses (SwIVs) isolated in Hanoi in 2016-2019 was carried out and showed the viral genetic diversity in Vietnamese swine. I found expansion of genotypic diversity in Vietnamese SwIV with 11 novel genotypes being identified. Phylogenetic analyses of the 2009 H1N1 pandemic like (H1N1pdm09) SwIVs identified four separate reverse-zoonotic transmissions of H1N1pdm09 virus from human to swine and showed the onward transmission of H1N1pdm09 virus in Vietnamese pig herds which resulted in emergence of two new reassortant viruses. The phylogenetic analysis also demonstrated the first evidence of the H1-!1a viruses detected in Asia. I investigated the time of introduction of H1-!1a SwIVs from North America to Vietnam and discussed a possible routes of introduction via importation of breeding hogs. I further summarized the spread of North American-like triple reassortant (TR) SwIVs in Asia that led to establishment of multiple TR lineages circulating in Vietnam.

I developed a systematic approach to utilize age-stratified seroprevalence to assess population immunity to inform pandemic risk assessment of prevailing SwIVs. Two serological surveys were done in Hong Kong and Shenzhen against multiple lineages of Chinese SwIVs and the results were modelled with inference on putative reproduction number (Rt) in the event of these viruses acquiring efficient transmissibility in humans. The results suggested that the preexisitng human population immunity is insufficient to prevent the spread of Eurasian H1N1 SwIVs and TR H1N2 SwIVs if they acquired efficient transmissibility in humans.

Many RT-PCR-based tests used in human influenza surveillance could not distinguish the Binh Duong-like (BD-like) H3 SwIVs from common human seasonal H3 infections and thus current surveillance would likely miss events zoonotic transmission with these viruses which are now common in China and Vietnam.