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bioRxiv · 10.1101/2023.10.30.564250

Nucleoprotein reassortment enhanced transmissibility of H3 1990.4.a clade influenza A virus in swine

Thomas, M. N.·Ciacci Zanella, G.·Cowan, B.·Caceres, C. J.·Rajao, D.·Perez, D. R.·Gauger, P. C.·Baker, A. L.·Anderson, T. K.
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Abstract

The increased detection of H3 C-IVA (1990.4.a) clade influenza A viruses (IAV) in U.S. swine in 2019 was associated with a reassortment event to acquire an H1N1pdm09 lineage nucleoprotein (pdmNP) gene, replacing a TRIG lineage NP (trigNP). We hypothesized that acquiring the pdmNP conferred a selective advantage over prior circulating H3 viruses with a trigNP. To investigate the role of the NP reassortment in transmission, we identified two contemporary 1990.4.a representative strains (NC/19 and MN/18) with different evolutionary origins of the NP gene. A reverse genetics system was used to generate wild-type (wt) strains and to swap the pdm and TRIG lineage NP genes, generating four viruses: wtNC/19-pdmNP, NC/19-trigNP, wtMN/18-trigNP, MN/18-pdmNP. Pathogenicity and transmission of the four viruses were compared in pigs. All four viruses infected 10 primary pigs and transmitted to 5 indirect contact pigs per group. Pigs infected via contact with MN/18-pdmNP shed virus two days earlier than pigs infected with wtMN/18-trigNP. The inverse did not occur for wtNC/19-pdmNP and NC/19-trigNP. These data suggest that reassortment to acquire a pdmNP gene improved transmission efficiency in the 1990.4.a, but this is likely a multigenic trait. Replacing a trigNP gene alone may not diminish the transmission of a wild-type virus sampled from the swine population. This study demonstrates how reassortment and subsequent evolutionary change of internal genes can result in more transmissible viruses that impact the detection frequency of specific HA clades. Thus, rapidly identifying novel reassortants paired with dominant HA/NA may improve prediction of strains to include in vaccines. ImportanceInfluenza A viruses (IAV) are composed of eight non-continuous gene segments that can reassort during coinfection of a host, creating new combinations. Some gene combinations may convey a selective advantage and be paired together preferentially. A reassortment event was detected in swine in the United States that involved the exchange of two lineages of nucleoprotein (NP) genes (trigNP to pdmNP) that became a predominant genotype detected in surveillance. Using a transmission study, we demonstrated that exchanging the trigNP for a pdmNP caused the virus to shed from the nose at higher levels and transmit to other pigs more rapidly. Replacing a pdmNP with a trigNP did not hinder transmission, suggesting that transmission efficiency depends on interactions between multiple genes. This demonstrates how reassortment alters IAV transmission and that reassortment events can provide an explanation for why genetically related viruses with different internal gene combinations experience rapid fluxes in detection frequency.

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Thomas, M. N., Ciacci Zanella, G., Cowan, B., Caceres, C. J., Rajao, D., Perez, D. R., Gauger, P. C., Baker, A. L., Anderson, T. K.. 2023-10-30. Nucleoprotein reassortment enhanced transmissibility of H3 1990.4.a clade influenza A virus in swine. https://doi.org/10.1101/2023.10.30.564250

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