The Effect of Global Spread, Epidemiology, and Control Strategies on the Evolution of the GI-19 Lineage of Infectious Bronchitis Virus

Abstract

The GI-19 lineage of infectious bronchitis virus (IBV) has emerged as one of the most impactful, particularly in the "Old World". Originating in China several decades ago, it has consistently spread and evolved, often forming independent clades in various areas and countries, each with distinct production systems and control strategies. This study leverages this scenario to explore how different environments may influence virus evolution. Through the analysis of the complete S1 sequence, four datasets were identified, comprising strains of monophyletic clades circulating in different continents or countries (e.g., Asia vs. Europe and China vs. Thailand), indicative of single introduction events and independent evolution. The population dynamics and evolutionary rate variation over time, as well as the presence and intensity of selective pressures, were estimated and compared across these datasets. Since the lineage origin (approximately in the mid-20th century), a more persistent and stable viral population was estimated in Asia and China, while in Europe and Thailand, a sharp increase following the introduction (i.e., 2005 and 2007, respectively) of GI-19 was observed, succeeded by a rapid decline. Although a greater number of sites on the S1 subunit were under diversifying selection in the Asian and Chinese datasets, more focused and stronger pressures were evident in both the European (positions 2, 52, 54, 222, and 379 and Thai (i.e., positions 10, 12, 32, 56, 62, 64, 65, 78, 95, 96, 119, 128, 140, 182, 292, 304, 320, and 323) strains, likely reflecting a more intense and uniform application of vaccines in these regions. This evidence, along with the analysis of control strategies implemented in different areas, suggests a strong link between effective, systematic vaccine implementation and infection control. However, while the overall evolutionary rate was estimated at approximately 10^-3 to 10^-4, a significant inverse correlation was found between viral population size and the rate of viral evolution over time. Therefore, despite the stronger selective pressure imposed by vaccination, effectively constraining the former through adequate control strategies can efficiently prevent viral evolution and the emergence of vaccine-escaping variants.

Keywords: IBV; environments; evolution; immunity; natural selection; phylodynamic; vaccine.

Figure 1

Maximum likelihood phylogenetic tree based on the selected S1 sequences. The Asian, European, and Thai clades are highlighted in red, blue, and green, respectively.

Figure 2

Left figure: mean and upper and lower 95HPD values of relative genetic diversity (Ne × t) of the Asian (red) and European (blue) GI-19 populations are reported over time. Right figure: mean and upper and lower 95HPD values are reported for each run.

Figure 3

Depiction of relative genetic diversity over time of the GI-19 lineage was calculated based on the Chinese and Thailand datasets. Mean values are represented as a black line, while 95HPD intervals have been displayed as red (China) or blue (Thailand) shaded areas.

Figure 4

Results of the rolling correlation coefficient analysis among viral population size and evolutionary rate for the (a) Asian, (b) European, (c) Chinese, and (d) Thai datasets. For each dataset, the upper panel reports the trend (centered and scaled) of both variables while in the bottom one, the heatmap reports the rolling correlation coefficients calculated for different years and window sizes. Coefficients that are not statistically significant (95% confidence level) are blank. The strength of the correlation has been color-coded. Line contours indicate similar values of rolling correlation coefficients. To increase the resulting robustness, analyses were performed starting from the mean estimation of tMRCA.

Figure 5

Different views of the quaternary structure of the IBV spike protein. The S1 regions have been edited to highlight different selective pressure features. (a) The sites under episodic diversifying selection in the Asian (red) and European (blue) datasets have been reported in the white and grey-colored monomer. The ochre monomer has been reported to depict the overall spike structure. (b) The same color scheme has been used to compare China (red) and Thailand (blue). A more detailed representation of the overall protein structure is reported in Supplementary animations S1 and S3. Images have been generated with the SWISS-MODEL web server and edited with Chimera.

Figure 6

Different views of the quaternary structure of the IBV spike protein. The S1 regions have been edited to highlight different selective pressure features. The dN/dS difference between (a) Europe and Asia and (b) Thailand and China datasets, calculated using FUBAR, is reported using a continuous color scale ranging from positive (red) to negative (blue) values. A more detailed representation of the overall protein structure is reported in Supplementary animations S2 and S4. Images have been generated with the SWISS-MODEL web server and edited with Chimera.