The genetic diversity and frequent emergence of novel genetic variants of porcine reproductive and respiratory syndrome virus type-2 (PRRSV) hinders control efforts, yet drivers of macro-evolutionary patterns of PRRSV remain poorly documented. Utilizing a comprehensive database of >20,000 orf5 sequences, our objective was to classify variants according to the phylogenetic structure of PRRSV co-circulating in the U.S., quantify evolutionary dynamics of sub-lineage emergence, and describe potential antigenic differences among sub-lineages. We subdivided the most prevalent lineage (Lineage 1, accounting for approximately 60% of available sequences) into eight sub-lineages. Bayesian coalescent SkyGrid models were used to estimate each sub-lineage’s effective population size over time. We show that a new sub-lineage emerged every 1 to 4 years and that the time between emergence and peak population size was 4.5 years on average (range: 2–8 years). A pattern of sequential dominance of different sub-lineages was identified, with a new dominant sub-lineage replacing its predecessor approximately every 3 years. Consensus amino acid sequences for each sub-lineage differed in key GP5 sites related to host immunity, suggesting that sub-lineage turnover may be linked to immune-mediated competition. This has important implications for understanding drivers of genetic diversity and emergence of new PRRSV variants in the U.S.

The repeated emergence of new genetic variants of PRRSV-2, the virus that causes porcine reproductive and respiratory syndrome (PRRS), reflects its rapid evolution and the failure of previous control efforts. Understanding spatiotemporal heterogeneity in variant emergence and spread is critical for future outbreak prevention. Here, we investigate how the pace of evolution varies across time and space, identify the origins of sub-lineage emergence, and map the patterns of the inter-regional spread of PRRSV-2 Lineage 1 (L1)—the current dominant lineage in the U.S. We performed comparative phylogeographic analyses on subsets of 19,395 viral ORF5 sequences collected across the U.S. and Canada between 1991 and 2021. The discrete trait analysis of multiple spatiotemporally stratified sampled sets (n = 500 each) was used to infer the ancestral geographic region and dispersion of each sub-lineage. The robustness of the results was compared to that of other modeling methods and subsampling strategies. Generally, the spatial spread and population dynamics varied across sub-lineages, time, and space. The Upper Midwest was a main spreading hotspot for multiple sub-lineages, e.g., L1C and L1F, though one of the most recent emergence events (L1A(2)) spread outwards from the east. An understanding of historical patterns of emergence and spread can be used to strategize disease control and the containment of emerging variants.

In this study, we compiled 84-year worth (1934–2017) of genomic and epidemiological data of foot-and-mouth disease virus (FMDV), and performed comprehensive analyses to determine its early origin and transmission route. We found that recombination is a key feature of FMDV, and that the genomic regions coding for structural and non-structural proteins have markedly different evolutionary histories, and evolve at different rates. Despite all of these differences, analyses of both structural and non-structural protein coding regions consistently suggested that the most recent common ancestor of FMDV could be dated back to the Middle Age, ~ 200 to 300 years earlier than previously thought. The ancestors of the Euro-Asiatic and SAT strains could be dated back to the mid-seventeenth century, and to the mid-fifteenth to mid-sixteenth century, respectively. Our results implicated Mediterranean counties as an early geographical origin of FMDV before spreading to Europe and subsequently to Asia and South America.

Glycosylation of proteins is a post-translational process where oligosaccharides are attached to proteins, potentially altering their folding, epitope availability, and immune recognition. In Porcine reproductive and respiratory syndrome virus-type 2 (PRRSV-2), positive selection pressure acts on amino acid sites potentially associated with immune escape through glycan shielding. Here, we describe the patterns of potential N-glycosylation sites over time and across different phylogenetic lineages of PRRSV-2 to better understand how these may contribute to patterns of coexistence and emergence of different lineages. We screened 19,179 PRRSV GP5 sequences (2004–2021) in silico for potential N-glycosylated sites. The emergence of novel combinations of N-glycosylated sites coincided with past PRRSV epidemics in the U.S. For lineage L1A, glycosylation at residues 32, 33, 44, 51, and 57 first appeared in 2012, but represented >62% of all L1A sequences by 2015, coinciding with the emergence of the L1A 1-7-4 strain that increased in prevalence from 8 to 86% of all L1A sequences from 2012 to 2015. The L1C 1-4-4 strain that emerged in 2020 also had a distinct N-glycosylation pattern (residues 32, 33, 44, and 51). From 2020 to 2021, this pattern was responsible for 44–47% of the L1C sequences, contrasting to <5% in years prior. Our findings support the hypothesis that antigenic evolution contributes to the sequential dominance of different PRRSV strains and that N-glycosylation patterns may partially account for antigenic differences amongst strains. Further studies on glycosylation and its effect on PRRSV GP5 folding are needed to further understand how glycosylation patterns shape PRRSV occurrence.

Porcine epidemic diarrhea virus (PEDV) emerged in the United States (U.S.) swine population in 2013, initiating an initial significant epidemic followed by a state of endemicity in the U.S. Despite continued monitoring, the epidemiology of PEDV during its endemic phase remains inadequately researched. Our study aimed to characterize the spatial–temporal distribution of postepidemic PEDV cases in the U.S. breeding herd and identify associated risk factors. Data from 1089 breeding farms in 27 states, reported to the Morrison Swine Health Monitoring Project from July 2014 to June 2021, were analyzed. We stratified the data into six U.S. regions and employed SaTScan for spatiotemporal permutation and cluster analysis. Survival analysis was used to assess risk factors. A notable seasonal clustering of PEDV cases was observed in winter (January–March; p = 0.001, relative risk = 2.2) with regional variation. Ten high‐rate spatial–temporal clusters (p < 0.05) were identified ranging from 2.5 to 833.7 km² and lasting 1–5 months, occurring in four regions between 2015 and 2021. For the study period, a total of 625 cases of PEDV were recorded on 372 farms. The total number of PEDV cases decreased from 95 breeding farms in 32 counties (2014–2015) to 53 farms in 28 counties (2020–2021), indicating an overall reduction in occurrence and spatial extent. Feed mitigants demonstrated a protective effect, significantly reducing the risk of PEDV occurrence (hazard ratio = 0.3, p = 0.003), while air filtration systems exhibited marginal benefits (hazard ratio = 0.3, p = 0.06). Other important risk factors included county farm density with farms in high‐density regions (>31 farms/100 km²) being 1.3 times more likely to experience outbreaks than in medium‐density regions (13–31 farms/1000 km²; p < 0.001). Additionally, farms in region E had higher odds of outbreaks compared to region B. The overall decline in PEDV cases and reduced spatial extent reflect industry efforts in postepidemic control and elimination. The protective effects of feed mitigants warrant further investigation. Our findings underscore the opportunity for coordinated efforts to eliminate PEDV in the U.S. and emphasize the need for comprehensive risk profiling associated with industry practices.

The United States (U.S.) swine industry has struggled to control porcine reproductive and respiratory syndrome (PRRS) for decades, yet the causative virus, PRRSV‐2, continues to circulate and rapidly diverges into new variants. In the swine industry, the farm is typically the epidemiological unit for monitoring, prevention, and control; breaking transmission among farms is a critical step in containing disease spread. Despite this, our understanding of farm transmission still is inadequate, precluding the development of tailored control strategies. Therefore, our objective was to infer farm‐to‐farm transmission links, estimate farm‐level transmissibility as defined by reproduction numbers (R), and identify associated risk factors for transmission using PRRSV‐2 open reading frame 5 (ORF5) gene sequences, animal movement records, and other data from farms in a swine‐dense region of the U.S. from 2014 to 2017. Timed phylogenetic and transmission tree analyses were performed on three sets of sequences (n = 206) from 144 farms that represented the three largest genetic variants of the virus in the study area. The length of inferred pig‐to‐pig infection chains that corresponded to pairs of farms connected via direct animal movement was used as a threshold value for identifying other feasible transmission links between farms; these links were then transformed into farm‐to‐farm transmission networks and calculated farm‐levelR‐values. The median farm‐level R was one (IQR = 1–2), whereas theRvalue of 28% of farms was more than one. Exponential random graph models were then used to evaluate the influence of farm attributes and/or farm relationships on the occurrence of farm‐to‐farm transmission links. These models showed that, even though most transmission events cannot be directly explained by animal movement, movement was strongly associated with transmission. This study demonstrates how integrative techniques may improve disease traceability in a data‐rich era by providing a clearer picture of regional disease transmission.