Cytokines and Viral Hemorrhagic Fever: Potential for Therapeutic Intervention

Findlay, James S.; Ulaeto, David O.; D’Elia, Riccardo V.

doi:10.2217/fvl.15.5

Cited by 5 publications

(5 citation statements)

References 89 publications

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“…While we provide evidence that co-infection with a helper virus does not mobilize eTIP1 to other tissues, a more extensive trial is needed to establish the safety of this approach in the context of co-circulating enteroviruses. A particularly important question is if eTIP1 treatment can enhance disease through the induction of a ''cytokine storm'' (Fajgenbaum and June, 2020;Findlay et al, 2015;Yuan et al, 2021). The mechanisms and dynamics of the induction of protective responses are limited by the number of time points and type of samples analyzed.…”

Section: Limitations Of the Studymentioning

confidence: 99%

A defective viral genome strategy elicits broad protective immunity against respiratory viruses

Xiao

Lidsky

Shirogane

et al. 2021

Cell

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RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wildtype virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short-and long-term protection against SARS-CoV-2 and other respiratory infections in animal models. ll

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Section: Limitations Of the Studymentioning

confidence: 99%

A defective viral genome strategy elicits broad protective immunity against respiratory viruses

Xiao

Lidsky

Shirogane

et al. 2021

Cell

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“…Cytokines including TNF- α, IFN- γ, IL-1β, IL-2, IL-6 and IL-10 have been linked to the pathogenesis of other viral hemorrhagic diseases, such as dengue [ 73 – 77 ], and Ebola [ 78 , 79 ]. However, data have so far been lacking as to whether cytokines facilitate the immune response in fighting infection, suppression of the immune response is part of EEHV pathogenesis, or whether over activation contributes to disease progression through a ‘cytokine storm’ that often occurs in the terminal stages of Ebola and other viral diseases [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cytokines including TNFα, IFNγ, IL-1β, IL-2, IL-6 and IL-10 have been linked to the pathogenesis of other viral hemorrhagic diseases, such as dengue [73][74][75][76][77], and Ebola [78,79].…”

Section: Plos Onementioning

confidence: 99%

Patterns of serum immune biomarkers during elephant endotheliotropic herpesvirus viremia in Asian and African elephants

et al. 2021

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Hemorrhagic disease (HD) caused by a group of elephant endotheliotropic herpesviruses (EEHV) is one of the leading causes of death for young elephants in human care. These viruses are widespread and typically persist latently in adult elephants with no negative effects; however, in juvenile Asian and more recently young African elephants, the onset of disease can be rapid and the mortality rate high. Measuring biomarkers associated with the immune response could be beneficial to understanding underlying disease processes, as well as the management of infection and HD. The goal of this study was to measure acute phase proteins and cytokines in serum collected from elephants infected with EEHV (13 Asian and 1 African) and compare concentrations according to presence, severity and outcome of disease. Serum amyloid A (SAA) and haptoglobin (HP) were higher in elephants with EEHV viremia than those without; concentrations increased with increasing viral load, and were higher in fatal cases compared to those that survived. In Asian elephants, SAA was also higher during EEHV1 viremia compared to EEHV5. Cytokine concentrations were typically low, and no statistical differences existed between groups. However, in individuals with detectable levels, longitudinal profiles indicated changes in tumor necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) that may reflect an immune response to EEHV infection. However, the overall low concentrations detected using previously validated assays do not support the presence of a ‘cytokine storm’ and suggest more work is needed to understand if sub-optimal immune responses could be involved in disease progression. These results highlight the potential benefit of measuring circulating biomarker concentrations, such as APPs and cytokines, to improve our understanding of EEHV viremia and HD, assist with monitoring the progression of disease and determining the impact of interventions.

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“…A common underlying mechanism in VHF is a massive production of proinflammatory cytokines. High levels of cytokines such as CXCL2, CXCL8, IL-6, TNF-α are usually found in the blood of severe yellow fever and dengue fever patients [ 84 , 85 ]. The role of neutrophils in severe YFV infection is unclear.…”

Section: Participation Of Neutrophils and Neutrophil-associated Molecules In Flaviviral Diseasesmentioning

confidence: 99%

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

Fontoura

Rocha

Marques

2021

Life

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Neutrophils are first-line responders to infections and are recruited to target tissues through the action of chemoattractant molecules, such as chemokines. Neutrophils are crucial for the control of bacterial and fungal infections, but their role in the context of viral infections has been understudied. Flaviviruses are important human viral pathogens transmitted by arthropods. Infection with a flavivirus may result in a variety of complex disease manifestations, including hemorrhagic fever, encephalitis or congenital malformations. Our understanding of flaviviral diseases is incomplete, and so is the role of neutrophils in such diseases. Here we present a comprehensive overview on the participation of neutrophils in severe disease forms evolving from flavivirus infection, focusing on the role of chemokines and their receptors as main drivers of neutrophil function. Neutrophil activation during viral infection was shown to interfere in viral replication through effector functions, but the resulting inflammation is significant and may be detrimental to the host. For congenital infections in humans, neutrophil recruitment mediated by CXCL8 would be catastrophic. Evidence suggests that control of neutrophil recruitment to flavivirus-infected tissues may reduce immunopathology in experimental models and patients, with minimal loss to viral clearance. Further investigation on the roles of neutrophils in flaviviral infections may reveal unappreciated functions of this leukocyte population while increasing our understanding of flaviviral disease pathogenesis in its multiple forms.

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Cytokines and Viral Hemorrhagic Fever: Potential for Therapeutic Intervention

Cited by 5 publications

References 89 publications

A defective viral genome strategy elicits broad protective immunity against respiratory viruses

A defective viral genome strategy elicits broad protective immunity against respiratory viruses

Patterns of serum immune biomarkers during elephant endotheliotropic herpesvirus viremia in Asian and African elephants

Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection

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