Variability in Susceptibility to Type I Interferon Response and Subgenomic RNA Accumulation Between Clinical Isolates of Dengue and Zika Virus From Oaxaca Mexico Correlate With Replication Efficiency in Human Cells and Disease Severity

Castro-Jiménez, Tannya; Gómez-Legorreta, Laura Cristina; López-Campa, Laura Alejandra; Martínez-Torres, Valeria; Alvarado-Silva, Marcos; Posadas-Mondragón, Araceli; Díaz-Lima, Nallely; Angulo-Mendez, Hilda Arcelia; Mejía‐Domínguez, Nancy R.; Vaca-Paniagua, Felipe; Ávila‐Moreno, Federico; García‐Cordero, Julio; Cedillo‐Barrón, Leticia; Aguilar-Ruíz, Sergio Roberto; Bustos-Arriaga, José

doi:10.3389/fcimb.2022.890750

Cited by 4 publications

(4 citation statements)

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“…In addition, inhibition of CHIKV replication was evaluated in human BJ skin fibroblasts (normal cells), since fibroblasts are susceptible to CHIKV infection following mosquito bite. Dermal fibroblasts induce the activation of innate immune responses such as IFNβ secretion, this has been described in HFF-1, HDF cell lines infected with dengue and Zika arboviruses [28][29][30] and in HT-1080 and HS 633T infected with CHIKV [31]. When treated with 100 μM NCAO, a decrease in viral replication was observed at 48 hpi (Figure 7), like what was observed in Vero and C6/36 cells.…”

Section: Discussionsupporting

confidence: 66%

Inhibition of chikungunya virus replication by N-ω-Chloroacetyl-L-Ornithine in C6/36, Vero cells and human fibroblast BJ

et al. 2023

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Background Polyamines are involved in several cellular processes and inhibiting their synthesis affects chikungunya virus (CHIKV) replication and translation, and, therefore, reduces the quantity of infectious viral particles produced. In this study, we evaluated the inhibition of CHIKV replication by N-ω-chloroacetyl-L-ornithine (NCAO), a competitive inhibitor of ornithine decarboxylase, an enzyme which is key in the biosynthesis of polyamines (PAs). Methods The cytotoxicity of NCAO was evaluated by MTT in cell culture. The inhibitory effect of CHIKV replication by NCAO was evaluated in Vero and C6/36 cells. The intracellular polyamines were quantified by HPLC in CHIKV-infected cells. We evaluated the yield of CHIKV in titres via the addition of PAs in Vero, C6/36 cells and human fibroblast BJ treated with NCAO. Results We found that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms ( p < 0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though it is predominantly spermidines and spermines which are present in infected cells. Inhibition of CHIKV replication was observed in human fibroblast BJ treated with 100 μM NCAO 24 h before and 48 h after the infection at a MOI 1. Conclusions NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero, C6/36 cells and human fibroblast BJ, suggesting that this compound is a possible antiviral agent for CHIKV.

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Section: Discussionsupporting

confidence: 66%

Inhibition of chikungunya virus replication by N-ω-Chloroacetyl-L-Ornithine in C6/36, Vero cells and human fibroblast BJ

et al. 2023

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“…Use of a full-length live attenuated DENV3 vaccine that induces B and T cell immune responses similar to those from natural infection facilitates the safe modeling of enhancement and protection [ 34 , 51 ]. Recent work suggests that the mechanism of attenuation of the TV003 monovalent vaccine components is increased sensitivity of the virus strain to type I interferon signaling, and this form of attenuation is also observed in clinical isolates [ 52 , 53 ]. Thus, markers associated with risk and protection will likely reflect those in natural infection.…”

Section: Discussionmentioning

confidence: 99%

Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine

Odio,

Lowman,

Law

et al. 2023

BMC Infect Dis

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Background The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes. Methods/Design This is a phase 1 trial wherein healthy adults with neutralizing antibodies to zero (seronegative), one non-DENV3 (heterotypic), or more than one (polytypic) DENV serotype will be vaccinated with the live attenuated DENV3 monovalent vaccine rDEN3Δ30/31-7164. We will examine how pre-vaccine host immunity influences the safety and immunogenicity of DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have a significant increase in the DENV1-4 neutralizing antibody geometric mean titer between days 0 and 28. Compared to the seronegative group, the polytypic group will have lower mean peak vaccine viremia, due to protection conferred by prior DENV exposure, while the heterotypic group will have higher mean peak viremia, due to mild enhancement. Secondary and exploratory endpoints include characterizing serological, innate, and adaptive cell responses; evaluating proviral or antiviral contributions of DENV-infected cells; and immunologically profiling the transcriptome, surface proteins, and B and T cell receptor sequences and affinities of single cells in both peripheral blood and draining lymph nodes sampled via serial image-guided fine needle aspiration. Discussion This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations. Trial Registration NCT05691530 registered on January 20, 2023.

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“…A large number of studies have also shown that the ability to efficiently antagonize the IFN response confers an important selective advantage to flaviviruses. There is therefore a correlation between the IFN resistance of a given virus and its replication efficiency, pathogenicity and/or epidemiological fitness (Keller et al, 2006;Manokaran et al, 2015;Xia et al, 2018;Castro-Jiménez et al, 2022).…”

Section: Ifn and Flaviviruses: From In Vitro Data To In Vivo Outcomesmentioning

confidence: 99%

Transmission and Infection of Arboviruses

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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Variability in Susceptibility to Type I Interferon Response and Subgenomic RNA Accumulation Between Clinical Isolates of Dengue and Zika Virus From Oaxaca Mexico Correlate With Replication Efficiency in Human Cells and Disease Severity

Cited by 4 publications

References 84 publications

Inhibition of chikungunya virus replication by N-ω-Chloroacetyl-L-Ornithine in C6/36, Vero cells and human fibroblast BJ

Inhibition of chikungunya virus replication by N-ω-Chloroacetyl-L-Ornithine in C6/36, Vero cells and human fibroblast BJ

Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine

Transmission and Infection of Arboviruses

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