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    Spatial and temporal transmission dynamics of respiratory syncytial virus in New Zealand before and after the COVID-19 pandemic.
    (Cold Spring Harbor Laboratory, 2024-07-17) Jelley L; Douglas J; O'Neill M; Berquist K; Claasen A; Wang J; Utekar S; Johnston H; Bocacao J; Allais M; de Ligt J; Ee Tan C; Seeds R; Wood T; Aminisani N; Jennings T; Welch D; Turner N; McIntyre P; Dowell T; Trenholme A; Byrnes C; SHIVERS investigation team; Webby R; French N; Winter D; Huang QS; Geoghegan JL
    Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was effectively eliminated from the community in New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of COVID-19. However, in April 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five times higher, and hospitalisations more than three times higher, than the typical seasonal pattern. In this study, we generated 1,471 viral genomes of both RSV-A and RSV-B sampled between 2015 and 2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV in New Zealand that affected a broader age group range compared to the usual pattern of RSV infections. This epidemic was due to an increase in RSV importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes in New Zealand. However, while a number of importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic seasonal outbreaks. These genomic clusters were temporally associated with the increase of migration in 2021 due to quarantine-free travel from Australia at the time. The closest genetic relatives to the New Zealand RSV genomes, when sampled, were viral genomes sampled in Australia during a large, off-season summer outbreak several months prior, rather than cryptic lineages that were sustained but not detected in New Zealand. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes.
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    Modeling RNA evolution : in-silico and in-vivo : a thesis presented for the degree of Master of Science in BioMathematics at Massey University, Palmerston North, New Zealand
    (Massey University, 2004) Matheson, James William
    We look at two aspects of the evolution of RNA. First we look at RNA replication dynamics in an early RNA world context. Experimental evidence (Spiegelman et al. 1965, Biebricher et al. 1981) shows that under some conditions RNA evolves towards small quickly replicating molecules. We investigate what conditions are sufficient for a population of RNA molecules to evolve towards a balanced population of molecules. This is a population not completely dominated by a single length of molecule. We consider two models: A linear model in which indel rate is inversely proportional to length and a game theory model in which reproductive efficiency depends on the distribution of molecule lengths within a population (this is linked to catalytic efficiency). Models are investigated using analytic, numerical and simulation methods. The linear model is not sufficient to support a population with balanced length distribution. Simulation methods show that the game theory model may support such a population. We next look at RNA evolution in the context of RNA virus evolution. Using virus samples taken over a thirty year period we investigate the evolution of Respiratory Syncytial Virus (RSV) in New Zealand. RSV most strongly affects infants and the elderly, causing cold like symptoms in mild cases and bronchiolitis or occasionally death in severe cases. New Zealand has a higher incidence of RSV bronchiolitis per head of population than many other developed countries. We compare New Zealand strains of the virus to those isolated overseas to investigate if New Zealand may have significantly different strains. We look at the evolution of the virus within New Zealand looking for evidence of antigenic drift, as well as analysing substitution rates and selection at individual codon sites. No evidence is found to suggest that New Zealand has significantly different strains of RSV from other countries. We conclude the higher rate of severe RSV in New Zealand must be caused by factors other than virus strain. The portion of the virus analysed shows strong evidence of being under positive selective pressure. This and other analyses suggest that RSV may be undergoing antigenic drift.