Cross-Species Interferon Signaling Boosts Microbicidal Activity within the Tick Vector

Smith, Alexis A.; Navasa, Nicolás; Yang, Xiuli; Wilder, Cara N.; Büyüktanir, Özlem; Marques, Adriana; Anguíta, Juan; Pal, Utpal

doi:10.1016/j.chom.2016.06.001

Cited by 54 publications

(91 citation statements)

References 28 publications

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“…burgdorferi , as detailed 28 . The infected ticks were fed on naïve mice (5 ticks per mouse, 3 mice per group) and fully engorged ticks were subjected to qRT-PCR analyses.…”

Section: Methodsmentioning

confidence: 99%

A protein-protein interaction dictates Borrelial infectivity

Thakur

Sharma

Chao

et al. 2017

Sci Rep

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Two Borrelia burgdorferi interacting proteins, BB0238 and BB0323, play distinct roles in pathogen biology and infectivity although a significance of their interaction remained enigmatic. Here we identified the polypeptide segment essential for BB0238-BB0323 interaction and examined how it supports spirochete infectivity. We show that the interaction region in BB0323 requires amino acid residues 22–200, suggesting that the binding encompasses discontinuous protein segments. In contrast, the interaction region in BB0238 spans only 11 amino acids, residues 120–130. A deletion of these 11 amino acids neither alters the overall secondary structure of the protein, nor affects its stability or oligomerization property, however, it reduces the post-translational stability of the binding partner, BB0323. Mutant B. burgdorferi isolates producing BB0238 lacking the 11-amino acid interaction region were able to persist in ticks but failed to transmit to mice or to establish infection. These results suggest that BB0238-BB0323 interaction is critical for post-translational stability of BB0323, and that this interaction is important for mammalian infectivity and transmission of B. burgdorferi. We show that saturation or inhibition of BB0238-BB0323 interaction could be studied in a luciferase assay, which could be amenable for future identification of small molecule inhibitors to combat B. burgdorferi infection.

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“…burgdorferi , as detailed 28 . The infected ticks were fed on naïve mice (5 ticks per mouse, 3 mice per group) and fully engorged ticks were subjected to qRT-PCR analyses.…”

Section: Methodsmentioning

confidence: 99%

A protein-protein interaction dictates Borrelial infectivity

Thakur

Sharma

Chao

et al. 2017

Sci Rep

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“…Tick salivary lectin pathway inhibitor (TSLPI) inhibits the human lectin complement pathway by interfering with the mannose binding lectin activity and enables transmission of Borrelia by protecting it from complement-mediated killing (Schuijt et al, 2011b; Wagemakers et al, 2016). Recently, Smith et al (2016) showed that I. scapularis respond to interferon gamma acquired in the blood meal when parasitizing on B. burgdorferi -infected mice, leading to the up-regulation of the Rho-like GTPase and induction of antimicrobial peptides to inhibit pathogen infection.…”

Section: Biological Processes Involved In Tick-pathogen Interactionsmentioning

confidence: 99%

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

Fuente

Antunes

Bonnet

et al. 2017

Front. Cell. Infect. Microbiol.

354

272

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Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases.

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“…However, the tick JAK-STAT pathway can respond to mammalian IFN-␥ imbibed with a blood meal when a pathogen is acquired from an infected mammal. This results in upregulation of antimicrobial peptides that reduce the pathogen burden in the tick (shown in the context of Borrelia burgdorferi infection of mice) (93). Vertebrate cytokines can also stimulate the mosquito midgut (94).…”

Section: Flavivirus Suppression Of Jak-stat In the Arthropod Vectormentioning

confidence: 99%

The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling

Best

2017

J Virol

205

159

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The vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. Their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with Zika virus (ZIKV) or West Nile virus in the Americas. Every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to ZIKV, antagonizes the host type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting that suppression of this pathway is an important determinant of infection. The most direct and potent viral inhibitor of this pathway is the nonstructural protein NS5. However, the mechanisms utilized by NS5 from different flaviviruses are often quite different, sometimes despite close evolutionary relationships between viruses. The varied mechanisms of NS5 as an IFN-I antagonist are also surprising given that the evolution of NS5 is restrained by the requirement to maintain function of two enzymatic activities critical for virus replication, the methyltransferase and RNA-dependent RNA polymerase. This review discusses the different strategies used by flavivirus NS5 to evade the antiviral effects of IFN-I and how this information can be used to better model disease and develop antiviral countermeasures.

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Cross-Species Interferon Signaling Boosts Microbicidal Activity within the Tick Vector

Cited by 54 publications

References 28 publications

A protein-protein interaction dictates Borrelial infectivity

A protein-protein interaction dictates Borrelial infectivity

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling

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