Journal Articles

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    An accumulated mutation gained in mosquito cells enhances Zika virus virulence and fitness in mice.
    (American Society for Microbiology, 2024-10-16) Fan X-X; Li R-T; Zhu Y-B; Chen Q; Li X-F; Cao T-S; Zhao H; Cheng G; Qin C-F; Heise MT
    Zika virus (ZIKV) remains a significant public health threat worldwide. A number of adaptive mutations have accumulated within the genome of ZIKV during global transmission, some of which have been linked to specific phenotypes. ZIKV maintains an alternating cycle of replication between mosquitoes and vertebrate hosts, but the role of mosquito-specific adaptive mutations in ZIKV has not been well investigated. In this study, we demonstrated that serial passaging of ZIKV in mosquito Aag2 cells led to the emergence of critical amino acid substitutions, including A94V in the prM protein and V153D and H401Y in the E protein. Further characterization via reverse genetics revealed that the H401Y substitution in the E protein did not augment viral replication in mosquitoes but significantly enhanced neurovirulence and lethality compared with those of the wild-type (WT) virus in mice. More importantly, the H401Y mutant maintained its virulence phenotype in mice after propagation in mosquitoes in mosquito-mouse cycle model. In particular, recombinant ZIKV harboring the H401Y substitution showed enhanced competitive fitness over WT ZIKV in various mammalian cells and mouse brains, but not in mosquito cells. Notably, the H401Y substitution in the ZIKV E protein has been detected in recent isolates derived from both mosquitoes and humans in Asia and the Americas. In summary, our findings not only identify a novel virulence determinant of ZIKV but also highlight the complexity of the relationship between the evolution of vector-borne viruses and their clinical outcome in nature.
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    The external workload of thoroughbred horse racing jockeys
    (MDPI (Basel, Switzerland), 2020-09-14) Legg K; Cochrane D; Gee E; Rogers C
    The objectives of this study were to quantify the external workload of thoroughbred racing jockeys in relation to their experience and racing performance. The number of rides of 786 jockeys and apprentices who rode in 407,948 flat and 13,648 jumps racing starts over 14 seasons were examined. Jockey work (ride numbers, seasons riding) and performance characteristics (race falls or wins) between cohorts with low (1-10), middle (10-200) and high (>200) numbers of rides per season were compared. Flat racing apprentices had more rides per season (25, interquartile range [IQR] 7-97 vs. 14, IQR 3-222, p < 0.001) but fewer rides per race day (2, IQR 1-4 vs. 4, IQR 2-6, p < 0.001) than flat racing jockeys. Flat racing jockeys in the high workload cohort (23%) were responsible for 83% of the race-day rides, riding in a median of 375 (IQR 283-520) races per season. These jockeys had half the fall rate (Incidence rate [IR] 1.0, 95% CI 0.9-1.1) and 1.4 times the success rates per 1000 rides (IR 98, 95% CI 97-99) than jockeys in the low and middle workload cohorts (p < 0.05). Most jockeys had light workloads, greater risk of injury and lower winning rates than the smaller cohort of jockeys with heavier workloads. This disparity in opportunity and success between cohorts indicates inefficiencies within the industry in recruitment and retention of jockeys. These data provide a foundation to further studies investigating jockey competition-specific fitness and its effect on both riding success and reducing injury risk.