Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage

Alwis, Ruklanthi de; Zellweger, Raphaël M.; Chua, Edmond; Wang, Lin‐Fa; Chawla, Tanu; Sessions, October M.; Marlier, Damien; Connolly, John E.; Messling, Véronika von; Anderson, Danielle E.

doi:10.1080/22221751.2021.1943536

Cited by 4 publications

(4 citation statements)

References 59 publications

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“…Inflammation has been shown with epithelial cell lines [37,38], but not in immunocompetent mice following intravenous inoculation [39]. Furthermore, viral kinetics and immune responses have been shown to be isolate-dependent [40,41]. Interestingly, the responses induced within the first 24 h following ex vivo challenge of vaginal tissue explants were parallel to those measured during the late infection stage in vaginal explants obtained from animals challenged vaginally.…”

Section: Discussionmentioning

confidence: 99%

Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques

et al. 2022

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Zika virus (ZIKV) cases continue to be reported, and no vaccine or specific antiviral agent has been approved for the prevention or treatment of infection. Though ZIKV is primarily transmitted by mosquitos, cases of sexual transmission and prolonged viral RNA presence in semen have been reported. In this observational study, we report the mucosal responses to sub-cutaneous and mucosal ZIKV exposure in cynomolgus macaques during acute and late chronic infection. Subcutaneous challenge induced a decrease in the growth factor VEGF in colorectal and cervicovaginal tissues 100 days post-challenge, in contrast to the observed increase in these tissues following vaginal infection. This different pattern was not observed in the uterus, where VEGF was upregulated independently of the challenge route. Vaginal challenge induced a pro-inflammatory profile in all mucosal tissues during late chronic infection. Similar responses were already observed during acute infection in a vaginal tissue explant model of ex vivo challenge. Non-productive and productive infection 100 days post-in vivo vaginal challenge induced distinct proteomic profiles which were characterized by further VEGF increase and IL-10 decrease in non-infected animals. Ex vivo challenge of mucosal explants revealed tissue-specific modulation of cytokine levels during the acute phase of infection. Mucosal cytokine profiles could represent biosignatures of persistent ZIKV infection.

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Section: Discussionmentioning

confidence: 99%

Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques

et al. 2022

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“…Different strains of ZIKV derived from the African and Asian lineages (MR766 and PE243 strains, respectively) have been found to exhibit distinct differences in their sequences and cytopathic effects in various experimental models involving cell culture, mice and non-human primates [ 15 , 16 , 17 , 18 , 19 ]. Notably, infection with ZIKV MR766 has been associated with higher rates of animal death, increased virus replication, and elevated levels of TNF-α, IL-6, and IL-1β in the brain [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells

Oliveira

Freire

Coelho

et al. 2023

Viruses

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In recent years, the Zika Virus (ZIKV) has caused pandemic outbreaks associated with a high rate of congenital ZIKV syndrome (CZS). Although all strains associated with worldwide outbreaks derive from the Asian lineage, the reasons for their enhanced spread and severity are not fully understood. In this study, we conducted a comparative analysis of miRNAs (miRNA-155/146a/124) and their cellular targets (SOCS1/3, SHP1, TRAF6, IRAK1), as well as pro- and anti-inflammatory and anti-viral cytokines (IL-6, TNF-α, IFN-γ, IL-10, and IFN-β) and peroxisome proliferator-activated receptor γ (PPAR-γ) expression in BV2 microglia cells infected with ZIKV strains derived from African and Asian lineages (ZIKVMR766 and ZIKVPE243). BV2 cells were susceptible to both ZIKV strains, and showed discrete levels of viral replication, with delayed release of viral particles without inducing significant cytopathogenic effects. However, the ZIKVMR766 strain showed higher infectivity and replicative capacity, inducing a higher expression of microglial activation markers than the ZIKVPE243 strain. Moreover, infection with the ZIKVMR766 strain promoted both a higher inflammatory response and a lower expression of anti-viral factors compared to the ZIKVPE243 strain. Remarkably, the ZIKKPE243 strain induced significantly higher levels of the anti-inflammatory nuclear receptor—PPAR-γ. These findings improve our understanding of ZIKV-mediated modulation of inflammatory and anti-viral innate immune responses and open a new avenue to explore underlining mechanisms involved in the pathogenesis of ZIKV-associated diseases.

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“…This may lead to chronic up-regulation of the T H 2 response and a low-grade inflammatory state which could give way to more severe arbovirus symptoms [15]. Akin to allergic reactions, arboviral infections are associated with increased systemic inflammation and upregulation of T H 2 cytokines [13, 16, 17]. During acute DENV infection, mast cells are strongly activated and may cause a dysfunctional immune response that can paradoxically lead to severe organ involvement and a higher viral load [17].…”

Section: Introductionmentioning

confidence: 99%

Allergies, body mass, and hospitalization due to arbovirus infection: A prospective surveillance study in Machala, Ecuador

Hargrave,

Sippy,

Cueva

et al. 2023

Epidemiol. Infect.

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Dengue, chikungunya, and Zika are arboviruses that cause 390 million infections annually. Risk factors for hospitalization are poorly understood. Communities affected by these diseases have an escalating prevalence of allergies and obesity, which are linked to immune dysfunction. We assessed the association of allergies or body mass with hospitalization for an arbovirus infection. From 2014 to 2017, we recruited participants with a clinical diagnosis of arbovirus infection. Arbovirus infections were laboratory-confirmed and allergies were self-reported. Mid-upper arm circumference (MUAC), weight, and height were measured. We used two logistic regression models to assess the relationships between hospitalization and allergies and between hospitalization and body mass (MUAC for participants <20 years old and body mass index (BMI) for adults ≥20 years old). Models were stratified by age group and adjusted for confounders. For allergies, 41 of 265 were hospitalized. There was no association between allergies and hospitalization. For body mass, 34 of 251 were hospitalized. There was a 43% decrease in hospitalization odds for each additional centimetre MUAC among children (aOR 0.566, 95% CI 0.252-1.019) and a 12% decrease in hospitalization odds for each additional BMI unit among adults (aOR 0.877, 95% CI 0.752-0.998). Our work encourages the exploration of the underlying mechanisms.

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Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage

Abstract: 2021): Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in Cynomolgus Macaques are modulated by strain-specificity within the Asian lineage, Emerging Microbes & Infections,

Cited by 4 publications

References 59 publications

Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques

Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques

ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells

Allergies, body mass, and hospitalization due to arbovirus infection: A prospective surveillance study in Machala, Ecuador

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