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Theses

Interactions hôte-pathogène lors de l'infection par un alphavirus de la truite arc-en-ciel

Abstract : Salmonid alphavirus (SAV) has a significant impact on salmon and trout farms. Recurrent outbreaks of SAV cause important economic losses with serious environmental consequences on wild stocks. Although the clinical and pathological signs of the infection are fairly well known, the molecular mechanisms involved are poorly described. During this thesis, we have demonstrated that the viral non-structural protein 2 (nsP2) efficiently blocks the induction of type I interferon, the first line of defense of the immune system during an infection. This inhibition depends on the localization of nsP2 in the nucleus of the host cell thanks to the two nuclear localization sequences (NLS) located in its C-terminal part. These results demonstrate a major role for nsP2 in the control of the host cell innate immune response by SAV. We also studied the effect of mutations in the E2 envelope protein on viral pathogenicity, using a recombinant virus available in the laboratory. This virus is highly attenuated and does not induce mortality during infection in rainbow trout. However, it is found at high titer in the blood of fishes at the peak of viremia. We have shown that, much like the wild-type virus, it causes a delay in the growth of infected fish. Although the tropism of both viruses was identical, the absence of mortality induced by the attenuated virus is linked to an earlier immune response of the infected fish following massive viral replication at day 12 post-infection. The results highlight the importance of the escape mechanisms to counter the interferon response for SAV and the need for an early antiviral response for the host to clear the infection.
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Submitted on : Thursday, January 27, 2022 - 12:56:11 PM
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  • HAL Id : tel-03545617, version 1

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Raphaël Jami. Interactions hôte-pathogène lors de l'infection par un alphavirus de la truite arc-en-ciel. Microbiologie et Parasitologie. Université Paris-Saclay, 2021. Français. ⟨NNT : 2021UPASB051⟩. ⟨tel-03545617⟩

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