Targeted mutational analysis to unravel the complexity of African horse sickness virus NS3 function in mammalian cells

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Authors

Ferreira-Venter, Linda
Venter, Eudri
Theron, Jacques
Van Staden, Vida

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Publisher

Elsevier

Abstract

The African horse sickness virus non-structural protein 3 (NS3) is involved in the final stages of infection. To gain insight into the function of different NS3 domains, we generated reverse genetics-derived mutants, each expressing a modified version of the protein. A functional comparison of these mutants to the wild-type virus in mammalian cells indicated the variable contribution of the different domains to the cytopathic effect and in ensuring effective virus trafficking and release. The transmembrane domains were determined as essential mediators of NS3 localisation, as the abnormal processing of these mutant proteins resulted in their nuclear localisation and interaction with NS1. NS3 cytoplasmic domain disruptions resulted in increased cytosolic virus particle accumulation and abnormal virion tethering to plasma membranes. Other aspects of infection were also affected, such as VIB formation and distribution of the outer capsid proteins. Overall, these results illustrate the intricate role of NS3 in the infection cycle.

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Keywords

Rous sarcoma virus (RSV), Pathway, Release, Gag, Trafficking, Lipid rafts, Insect cell, African horsesickness virus (AHSV), Bluetongue virus (BTV), Non-structural protein 3 (NS3), Reverse genetics, Virus trafficking, Virus release, Non-structural protein 1 (NS1), Protein functional domains

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Citation

Ferreira-Venter, L., Venter, E., Theron, J. et al. 2019, 'Targeted mutational analysis to unravel the complexity of African horse sickness virus NS3 function in mammalian cells', Virology, vol. 531, pp. 149-161.