Biology subjects

Thomas, M. N.

Publications and source records attributed to Thomas, M. N..

4 recordsLinked to original sources

bioRxiv2024

Active surveillance for influenza A virus in swine reveals within-farm reassortment and cocirculation of distinct subtypes and genetic clades

Influenza A virus (IAV) is one of the three most frequently detected respiratory pathogens in swine. A passive IAV in swine surveillance system in the United States (U.S.) provides aggregated national metrics to quantify spatial and temporal changes in genetic diversity. However, swine production is not homogenous: production systems vary in size and management strategies that affect the transmission and evolution of IAV. To assess the impact of fine-scale variation in swine production on IAV transmission, we conducted active surveillance on sow farms and linked nurseries from 4 U.S. production systems for up to 14 monthly collections. From IAV-positive samples, we obtained 85 complete HA sequences, and of these, we successfully assembled 62 whole genomes with associated epidemiological information. To infer transmission and evolution, we conducted Bayesian phylodynamic analyses and detected six genetic clades from four HA lineages: the H1 1A classical swine, the H1 1B human-seasonal, and the H3 2010.1 and 1990.4 lineages. The 1B and H3 1990.4 strains showed evidence of transmission from sow farm to nursery. In contrast, 1A and H3 2010.1 viruses were detected in nurseries without detection in a linked sow farm. We also detected seven separate human-to- swine transmission events in the H1N1 pandemic clade (1A.3.3.2) in sow and nursery sites. Our data demonstrated that nursery sites were infected with IAV that was both linked and unlinked to the sow farm. These data suggest that control efforts may be impacted by subclinical IAV transmission in the breeding herd, the mixing of sow farm sources at the nursery, regional spread of new strains, and human-to-swine transmission. Regular surveillance activities within production systems provide the ability to match vaccine components to circulating diversity, thereby minimizing the opportunity for novel reassorted viruses to emerge and impact animal health.

bioinformatics↗

bioRxiv2024

Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle

Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird-to-cattle transmission episode. The movement of asymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers in virus populations were detected at low frequency that may lead to changes in transmission efficiency and phenotype after evolution in dairy cattle. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations.

microbiology↗

bioRxiv2024

2018-2019 human seasonal H3N2 influenza A virus spillovers into swine with demonstrated virus transmission in pigs were not sustained in the pig population

Human seasonal H3 3C3a clade influenza A viruses (IAV) were detected in four U.S. pigs from commercial swine farms in Michigan, Illinois, and Virginia in 2019. To evaluate the relative risk of this spillover to the pig population, whole genome sequencing and phylogenetic characterization was conducted and revealed all eight viral gene segments were closely related to 2018-2019 H3N2 human seasonal IAV. Next, a series of in vitro viral kinetics, receptor binding, and antigenic characterization studies were performed using a representative A/swine/Virginia/A02478738/2018(H3N2) (SW/VA/19) isolate. Viral replication kinetic studies of SW/VA/19 demonstrated less efficient replication curves than all ten swine H3N2 viruses tested, but higher than three human H3N2 strains. Serial passaging experiments of SW/VA/19 in swine cells did not increase virus replication, but changes at HA amino acid positions 9 and 159 occurred. In swine transmission studies, wild type SW/VA/19 was shed in nasal secretions and transmitted to all indirect contact pigs, whereas the human seasonal strain A/Switzerland/9715293/2013(H3N2) from the same 3C3a clade failed to transmit. SW/VA/19 induced minimal macroscopic and microscopic lung lesions. Collectively these findings demonstrate that these human seasonal H3N2 3C3a-like viruses did not require reassortment with endemic swine IAV gene segments, impacting virus shedding and transmission in pigs. Limited detections in the U.S. pig population in the subsequent period of time suggests a yet unknown restriction factor likely limiting the spread of these viruses in the U.S. pig population. IMPORTANCEInterspecies human-to-swine IAV transmission occurs globally and contributes to increased IAV diversity in pig populations. We present data that a swine isolate from a 2018-2019 human-to-swine transmission event was shed for multiple days in challenged and contact pigs. By characterizing this introduction through bioinformatic, molecular, and animal experimental approaches, these findings better inform animal health practices and in vaccine decision-making. Since wholly human seasonal H3N2 viruses in the U.S. were not previously identified as being transmissible in pigs (i.e. reverse zoonosis), these findings reveal the interspecies barriers for transmission to pigs may not require significant changes to all human seasonal H3N2.

microbiology↗

bioRxiv2023

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

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.

microbiology↗