Head Start Immunity: Characterizing the Early Protection of C Strain Vaccine Against Subsequent Classical Swine Fever Virus Infection

McCarthy, Ronan R.; Everett, Helen; Graham, Simon P.; Steinbach, Falko; Crooke, Helen

doi:10.3389/fimmu.2019.01584

Cited by 14 publications

(15 citation statements)

References 57 publications

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“…Therefore, we speculated that ISG15 might be induced by CSFV in an IFN-independent manner in PAMs, which will be further verified in future studies. Similar results were obtained in research of Vaccine-Cstrain; the ISG15 pathway was activated in response to Vaccine C-strain and ISG15 played a role in the rapid and early protection conferred by Vaccine C-strain [27]. In further research, we will test ISG15 effects on more CSFV genotypes to perfect the mechanisms of ISG15.…”

Section: Discussionsupporting

confidence: 76%

Antiviral activity of ISG15 against classical swine fever virus replication in porcine alveolar macrophages via inhibition of autophagy by ISGylating BECN1

Wang

Zheng

et al. 2020

Vet Res

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Interferons (IFNs) induce the expression of interferon-stimulated genes (ISGs) for defense against numerous viral infections, including classical swine fever virus (CSFV). However, the mechanisms underlying the effect of ISGs on CSFV infection are rarely reported. In this study, we demonstrate that IFN-α treatment induces upregulation of ISG15 and thus attenuates CSFV replication. To determine whether ISG15 is critical for controlling CSFV replication, we established porcine alveolar macrophages (PAMs) with stable overexpression or knockdown of ISG15. Overexpression of Flag-ISG15 significantly prevented CSFV replication, whereas loss of ISG15 led to abnormal proliferation of CSFV. Furthermore, upregulated ISG15 promoted beclin-1 (BECN1) ISGylation and dysfunction and subsequently inhibited autophagy, which is indispensable for CSFV replication. In addition, HECT and RLD domain containing E3 ubiquitin protein ligase 5 (HERC5), which functions to catalyze conjugation of ISG15 protein, was confirmed to interact with BECN1. Collectively, these results indicate that IFN-α restricts CSFV replication through ISG15-mediated BECN1 ISGylation and autophagy inhibition, providing insight into the mechanism of CSFV replication control by type I IFN. This mechanism may not be the only antiviral mechanism of ISG15; nonetheless, this study may contribute to the development of CSFV treatment and prevention strategies.

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Section: Discussionsupporting

confidence: 76%

Antiviral activity of ISG15 against classical swine fever virus replication in porcine alveolar macrophages via inhibition of autophagy by ISGylating BECN1

Wang

Zheng

et al. 2020

Vet Res

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“…[36][37][38][39] Preliminary in vitro data suggest potential in the application of both rhIFNα and Zelnate in the treatment of clinical EEHV infections and give a plausible mode of action to justify their use. 40 41 Although EEHVs are likely to possess IFN-evasion strategies as described in other herpesviruses, [42][43][44] the concept of head-start immunity has been proposed, 45 whereby these viral defences can be pre-empted and, with sufficient and timely activation of the IFN system, can overcome infection, as highlighted by IFN-based treatment strategies for chronic hepatitis B virus. 46 EEHV-HD is thought to be the result of primary infection in immunologically naive animals, following the decline of maternally derived antibodies.…”

Section: Discussionmentioning

confidence: 99%

Use of immunostimulants in the successful treatment of a clinical EEHV1A infection in an Asian elephant (Elephas maximus)

Drake

Haycock

Dastjerdi

et al. 2020

Vet Record Case Reports

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Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) poses a significant threat to the captive population of juvenile Asian elephants (Elephas maximus) and also affects elephants in the wild. In human and veterinary medicine, increasing attention is returning to the interferon system, a crucial mediator in the immune response for control of infection. We describe the first reported use of the Zelnate DNA immunostimulant and recombinant human interferon alpha (rhIFNα) as additional medications in the successful treatment of a case of EEHV1A-HD in a juvenile Asian elephant at a UK zoo. Despite an exponential rise in viraemia to a peak of 2.82×106 viral genomic equivalents/ml, only mild clinical signs developed and the calf survived with no adverse effects attributed to the novel treatments. This case is compared with a previous fatal case within the same herd where Zelnate and rhIFNα were not given.

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“…The emergence of a local CD8 + T cell response in the tonsil following C-strain vaccination is supported by a recent transcriptional analysis of tonsil tissue. Here, tissue from C-strain vaccinated pigs demonstrated an upregulation of eomes, a transcription factor, known to play a key role in the differentiation of effector CD8 T cells [48].…”

Section: Discussionmentioning

confidence: 84%

Activation of Dendritic Cells in Tonsils Is Associated with CD8 T Cell Responses following Vaccination with Live Attenuated Classical Swine Fever Virus

Soldevila

Edwards

Graham

et al. 2021

IJMS

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Classical swine fever (CSF) is a highly contagious disease caused by the classical swine fever virus (CSFV). The live attenuated C-strain vaccine is highly efficacious, initiating protection within several days of delivery. The vaccine strain is detected in the tonsil early after inoculation, yet little is known of the role that tonsillar immune cells might play in initiating protection. Comparing the C-strain vaccine with the pathogenic CSFV Alfort-187 strain, changes in the myeloid cell compartment of the tonsil were observed. CSFV infection led to the emergence of an additional CD163+CD14+ cell population, which showed the highest levels of Alfort-187 and C-strain infection. There was also an increase in both the frequency and activation status (as shown by increased MHC-II expression) of the tonsillar conventional dendritic cells 1 (cDC1) in pigs inoculated with the C-strain. Notably, the activation of cDC1 cells coincided in time with the induction of a local CSFV-specific IFN-γ+ CD8 T cell response in C-strain vaccinated pigs, but not in pigs that received Alfort-187. Moreover, the frequency of CSFV-specific IFN-γ+ CD8 T cells was inversely correlated to the viral load in the tonsils of individual animals. Accordingly, we hypothesise that the activation of cDC1 is key in initiating local CSFV-specific CD8 T cell responses which curtail early virus replication and dissemination.

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Head Start Immunity: Characterizing the Early Protection of C Strain Vaccine Against Subsequent Classical Swine Fever Virus Infection

Cited by 14 publications

References 57 publications

Antiviral activity of ISG15 against classical swine fever virus replication in porcine alveolar macrophages via inhibition of autophagy by ISGylating BECN1

Antiviral activity of ISG15 against classical swine fever virus replication in porcine alveolar macrophages via inhibition of autophagy by ISGylating BECN1

Use of immunostimulants in the successful treatment of a clinical EEHV1A infection in an Asian elephant (Elephas maximus)

Activation of Dendritic Cells in Tonsils Is Associated with CD8 T Cell Responses following Vaccination with Live Attenuated Classical Swine Fever Virus

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