Mechanisms of Immune Evasion by Ebola Virus

Bhattacharyya, Suchita

doi:10.1007/978-3-030-67452-6_2

Cited by 9 publications

(5 citation statements)

References 78 publications

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“…The evasion of the immune system by viruses has been recognized for some time. 57 , 58 In general, viruses utilize three main immune evasion strategies 59 , 60 , 61 , 62 : (1) impairment of the humoral immune response; (2) Interruption of the cellular immune response; (3) impairment of immune effectors such as cytokines and apoptosis‐related proteins. The humoral immune response mediates the production of antibodies against the virus.…”

Section: Immune Evasion Of Sars‐cov‐2 Omicronmentioning

confidence: 99%

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

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New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) constantly emerge through unmitigated spread of the virus in the ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), the latest variant of concern (VOC), has so far shown exceptional spread and infectivity and has established itself as the dominant variant in recent months. The SARS‐CoV‐2 spike glycoprotein is a key component for the recognition and binding to host cell angiotensin‐converting enzyme 2 receptors. The Omicron variant harbors a cluster of substitutions/deletions/insertions, and more than 30 mutations are located in spike. Some noticeable mutations, including K417N, T478K, N501Y, and P681H, are shared with the previous VOCs Alpha, Beta, Gamma, or Delta variants and have been proven to be associated with higher transmissibility, viral infectivity, and immune evasion potential. Studies have revealed that the Omicron variant is partially resistant to the neutralizing activity of therapeutic antibodies and convalescent sera, which poses significant challenges for the clinical effectiveness of the current vaccines and therapeutic antibodies. We provide a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant. This review, therefore, aims to provide information for further research efforts to prevent and contain the impact of new VOCs during the ongoing pandemic.

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Section: Immune Evasion Of Sars‐cov‐2 Omicronmentioning

confidence: 99%

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

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“…A single immunization of replication-competent rVSV∆G-LASV-GPC conferred complete protection in NHPs against lethal LASV infection 21 . To be effective, rVSV∆G-LASV-GPC needs to be administered at a high dose (>10 7 plaque-forming units), which may raise concerns about VSV vector-associated side effects 54,55 19,21 . In some cases, virion surface protein-binding antibodies induced by viral infection or vaccine inoculation increase virion infectivity and lead to more severe disease 59,60 .…”

Section: Discussionmentioning

confidence: 99%

An mRNA-LNP-based Lassa virus vaccine induces protective immunity in mice

Hashizume

Takashima

Iwasaki

2023

Preprint

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The mammarenavirus Lassa virus (LASV) causes the life-threatening hemorrhagic fever disease, Lassa fever. The lack of licensed medical countermeasures against LASV underscores the urgent need for the development of novel LASV vaccines, which has been hampered by the requirement for a biosafety level 4 facility to handle live LASV. Here, we investigated the efficacy of mRNA-lipid nanoparticle (mRNA-LNP)-based vaccines expressing the LASV glycoprotein precursor (LASgpc) or the nucleoprotein (LCMnp) of the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), in mice using recombinant (r) LCMV expressing a modified LASgpc and wild-type rLCMV. Two doses of LASgpc- or LCMnp-mRNA-LNP administered intravenously or intramuscularly protected mice from a lethal challenge with rLCMVs. Negligible levels of LASgpc-specific antibodies were induced in mRNA-LNP-immunized mice, but robust LASgpc- and LCMnp-specific CD8+ T cell responses were detected. Our findings and surrogate mouse models of LASV infection provide a critical foundation for the rapid development of mRNA-LNP-based LASV vaccines.

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“…Accumulating evidence suggests that EBOV has established multiple ways to antagonize host innate immune responses to maintain viral replication. Several EBOV proteins (VP35, VP24, GP, VP30 and VP40) are known to participate in host immune evasion to facilitate viral replication and pathogenesis (Audet & Kobinger, 2015; Bhattacharyya, 2021; Cantoni & Rossman, 2018). VP35 was demonstrated to suppress IFN-I production by inhibiting IRF3/7 phosphorylation, disrupting DC maturation, and facilitating the escape of immune sensation by dsRNA (Basler, 2015; Cardenas et al, 2006; Messaoudi, Amarasinghe, & Basler, 2015; Prins et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…VP30 and VP40 suppress RNA silencing by interacting with Dicer and modulating RNA interference components via exosomes, respectively(Fabozzi, Nabel, Dolan, & Sullivan, 2011;Pleet, DeMarino, Lepene, Aman, & Kashanchi, 2017). VP24 and GP are also known to block IFN-I signaling by hiding MHC-1 on the cell surface and counteracting tetherin or interfering with established immune responses by adsorbing antibodies against GP, respectively(Audet & Kobinger, 2015;Bhattacharyya, 2021).Viral IBs are a characteristic of cellular EBOV infection and are important sites for viral RNA replication, and NP and VP35 are extremely critical proteins for the formation of IBs structures(Hoenen et al, 2012). However, whether viral IBs are involved in antagonizing IFN-I production during EBOV trVLPs infection has not yet been reported.…”

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confidence: 99%

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Ebola Virus Sequesters IRF3 in Viral Inclusion Bodies to Evade Host Antiviral Immunity

Zhu

Jin

Wang

et al. 2023

Preprint

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Viral inclusion bodies (IBs) are commonly formed during the replication of Ebola virus (EBOV) in infected cells, but their role in viral immune evasion has rarely been explored. Here, we found that interferon regulatory factor 3 (IRF3), but not TANK-binding kinase 1 (TBK-1) or IκB kinase epsilon (IKKϵ), was recruited and sequestered in viral IBs when the cells were infected by EBOV transcription- and replication-competent virus-like particles (trVLPs). NP/VP35-induced IBs formation was critical for IRF3 recruitment and sequestration, probably through STING interaction. Consequently, the association of TBK1 and IRF3, which plays a vital role in type I interferon (IFN-I) induction, was blocked by EBOV trVLPs infection. Additionally, IRF3 phosphorylation and nuclear translocation induced by Sendai virus (SeV) or poly(I:C) stimulation were also suppressed by EBOV trVLPs. Furthermore, downregulation of STING significantly attenuated VP35-promoted IRF3 accumulation in IBs. Viral proteins by which IBs-like structures could be formed were demonstrated to be much more potent in IFN-I antagonism than the expression of the IFN-I antagonist VP35 only. These results suggested a novel immune evasion mechanism by which EBOV evades host innate immunity.

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Mechanisms of Immune Evasion by Ebola Virus

Cited by 9 publications

References 78 publications

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

An mRNA-LNP-based Lassa virus vaccine induces protective immunity in mice

Ebola Virus Sequesters IRF3 in Viral Inclusion Bodies to Evade Host Antiviral Immunity

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