Antiviral Cytokine Response in Neuroinvasive and Non-Neuroinvasive West Nile Virus Infection

Židovec-Lepej, Snježana; Vilibić-Čavlek, Tatjana; Barbić, Ljubo; Ilić, Maja; Savić, Vladimir; Tabain, Irena; Ferenc, Thomas; Grgić, Ivo; Gorenec, Lana; Bogdanić, Maja; Stevanović, Vladimir; Sabadi, Dario; Perić, Ljiljana; Potočnik-Hunjadi, Tanja; Dvorski, Elizabeta; Butigan, Tamara; Capak, Krunoslav; Listeš, Eddy; Savini, Giovanni

doi:10.3390/v13020342

Cited by 16 publications

(26 citation statements)

References 45 publications

(61 reference statements)

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“…Furthermore, neurotropic/neuroinvasive WNV infection has been associated with altered blood-brain barrier (BBB) permeability with a subsequent release of IFN-γ and other proinflammatory cytokines ( 29 ). Accordingly, a recent observational clinical study demonstrated increased concentrations of the key anti-viral/proinflammatory cytokines interleukin-6 (IL-6) and IFN-γ in cerebrospinal fluid (CSF) samples of patients with neuroinvasive WNV infection ( 30 ). Finally, in a preclinical rodent model of recurrent neuroinvasive HSV-1 infection, expression of neuroinflammatory cytokines, such as IL-1β and IL-6, in the hippocampus of HSV-1 infected mice was correlated with an increased incidence of cognitive deficits ( 31 ).…”

Section: Infection Of the Brain: Chronicity Neuronal Activity And Cognitionmentioning

confidence: 99%

SARS-CoV-2, Trait Anxiety, and the Microbiome

et al. 2021

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During the COVID-19 pandemic, research on the relationships between the virus and its human host has become fundamental to understand this pathology and its effects. Attaining this profound understanding is critical for the effective containment and treatment of infections caused by the virus. In this review, we present some possible mechanisms by which psychopathological symptoms emerge following viral infections of the central nervous system (CNS). These proposed mechanisms are based on microbial communication and the induced priming of microglial antibody activation within the CNS through Toll-like receptor signaling. In this process, chronic microglial activation causes increased glutamate release in virally-altered, high-density neuronal structures, thereby modulating cognitive networks and information integration processes. This modulation, in turn, we suggest, affects the accuracy of sensory integration and connectivity of major control networks, such as the default mode network. The chronic activation of immunological responses and neurochemical shifts toward an elevated glutamate/gamma-aminobutyric acid ratio lead to negative reinforcement learning and suboptimal organismic functioning, for example, maintaining the body in an anxious state, which can later become internalized as trait anxiety. Therefore, we hypothesize that the homeostatic relationship between host, microbiome, and virome, would be decisive in determining the efficiency of subsequent immunological responses, disease susceptibility, and long-term psychopathological effects of diseases that impact the CNS, such as the COVID-19.

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Section: Infection Of the Brain: Chronicity Neuronal Activity And Cognitionmentioning

confidence: 99%

SARS-CoV-2, Trait Anxiety, and the Microbiome

et al. 2021

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“…Recently, we described the expression patterns of cytokines in paired CSF and serum samples collected from 37 WNV NID patients after a median of 5 days since the onset of symptoms, and in the serum of patients with WNV fever. A well-defined pattern of cytokine expression that included a high intrathecal synthesis of IL-6; lack of significant differences in the serum vs. CSF concentrations of IL-13, IL-9, IL-10, IFN-γ, and IL-22; as well as by the absence of IL-2, IL-4, TNF-α, and Th17 cytokines in the CSF was observed [36]. The present study results, focusing specifically on severe WNV NID, have shown a consistent expression of IL-6 in the CSF and serum.…”

Section: Discussionmentioning

confidence: 88%

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes

Santini

Haberle²,

Lepej

et al. 2022

Pathogens

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West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.

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“…In the CSF, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appeared to be concentrated mainly in the periphery [42].…”

Section: Wnv Infections In Humansmentioning

confidence: 84%

Emerging Trends in the West Nile Virus Epidemiology in Croatia in the ‘One Health’ Context, 2011–2020

et al. 2021

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West Nile virus (WNV) is one of the most widely distributed (re-)emerging arboviruses. In Croatia, acute WNV infections as well as seropositivity were detected in humans, horses, birds and poultry. Although serologic evidence of WNV human infections dates back to the 1970s, no clinical cases were reported until 2012. WNV outbreaks, as well as sporadic infections, were continuously recorded in continental Croatian counties from 2012 to 2018. In addition, acute asymptomatic infections (IgM antibodies) in horses have been regularly notified in continental regions since 2012, while seropositive horses (seroprevalence rates 3.7–21.4%) were detected in both continental and coastal regions. Moreover, WNV seropositivity in poultry (1.8–22.9%) was reported from 2013 to 2020. During the largest WNV outbreak in 2018, WNV RNA was detected for the first time in two dead goshawks (Accipiter gentilis) from the same aviary in North-West Croatia, while WNV antibodies were found in one buzzard (Butteo butteo) from the same region. In addition, WNV RNA was detected in a dead blackbird (Turdus merula) at the Croatian littoral. The phylogenetic analysis of 11 strains detected in urine samples of patients with neuroinvasive disease and 1 strain detected in a goshawk showed circulation of WNV lineage 2. Thus far, WNV has not been detected in mosquitoes in Croatia.

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Antiviral Cytokine Response in Neuroinvasive and Non-Neuroinvasive West Nile Virus Infection

Cited by 16 publications

References 45 publications

SARS-CoV-2, Trait Anxiety, and the Microbiome

SARS-CoV-2, Trait Anxiety, and the Microbiome

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes

Emerging Trends in the West Nile Virus Epidemiology in Croatia in the ‘One Health’ Context, 2011–2020

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