Phenotyping and susceptibility of established porcine cells lines to African Swine Fever Virus infection and viral production

Sánchez, Elena González; Riera, Elena; Nogal, Marisa; Gallardo, Carmina; Fernández, Paloma; Bello-Morales, Raquel; Löpez‐Guerrero, José Antonio; Chitko-McKown, Carol G.; Richt, Jürgen A.; Revilla, Yolanda

doi:10.1038/s41598-017-09948-x

Cited by 45 publications

(44 citation statements)

References 60 publications

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“…Both strains infected all subsets tested, but infection of macrophages with NH/P68 resulted in higher virus titers and higher viral genome copies in culture supernatants compared to the virulent 22653/14. A similar trend was observed in previous studies on monocytes, monocyte-derived dendritic cells (moDC) [17], monocyte-derived macrophages [3], porcine alveolar macrophages (PAM) and another porcine cell line (WSL) [18], suggesting that this attenuated strain possess mechanisms to more efficiently replicate in myeloid cells, at least in vitro. Differences between macrophage subsets were also observed.…”

Section: Discussionsupporting

confidence: 87%

Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages

et al. 2020

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African swine fever (ASF) poses a severe threat to the global pig industry for which currently there is no available vaccine. The aetiological ASF virus (ASFV) has a predilection for cells of the myeloid lineage, however little is known about its interaction with polarised macrophages. This study focused on the in vitro interactions of porcine monocyte-derived un-activated (moMΦ), classically (moM1), alternatively (moM2), and IFN-α-activated macrophages with two genotype I ASFV strains: virulent 22653/14 and attenuated NH/P68. At a high multiplicity of infection, NH/P68, but not 22653/14, presented a reduced ability to infect moM1 and IFN−α-activated moMΦ compared to moMΦ. IFN-α activation resulted in a dose-dependent reduction in the proportion of ASFV-infected cells. Both strains replicated efficiently in all the subsets. While higher levels of IL-1α, IL-1β, and IL-18 were secreted by NH/P68-infected moM1 compared to 22653/14, both strains negatively affected moMΦ ability to release IL-6, IL-12, TNF-α in response to classical activation or stimulation with a TLR2 agonist. Our results suggest that ASFV 22653/14 covertly replicates in macrophages, compromising the development of effective immune responses. Attenuated NH/P68 has partially lost these mechanisms, which may enhance immune surveillance. A better understating of these mechanisms should aid the rational design of live attenuated ASFV vaccines.

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Section: Discussionsupporting

confidence: 87%

Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages

et al. 2020

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“…However, the role of CD163 in ASFV infection remains controversial since it was recently published that in non-permissive cells, CD163 expression is not enough to increase susceptibility to ASFV [ 11 ], and that CD163-knockdown pigs are not resistant to infection with ASFV Georgia 2007/1 [ 12 ]. These observations are in line with a recent study where NHV/P68-ASFV was efficiently produced after the infection of WSL cells despite only about 6% of the cells being positive for CD163, indicating that this receptor is not essential for ASFV infection in several cases [ 13 ].…”

Section: Mechanisms Of Asfv Entrysupporting

confidence: 91%

Mechanisms of Entry and Endosomal Pathway of African Swine Fever Virus

Sánchez¹,

Pérez-Núñez

Revilla

2017

Vaccines

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African Swine Fever Virus (ASFV) causes a serious swine disease that is endemic in Africa and Sardinia and presently spreading in Russia and neighboring countries, including Poland and recently, the Czech Republic. This uncontrolled dissemination is a world-wide threat, as no specific protection or vaccine is available. ASFV is a very complex icosahedral, enveloped virus about 200 nm in diameter, which infects several members of pigs. The virus enters host cells by receptor-mediated endocytosis that depends on energy, vacuolar pH and temperature. The specific receptor(s) and attachment factor(s) involved in viral entry are still unknown, although macropinocytosis and clathrin-dependent mechanisms have been proposed. After internalization, ASFV traffics through the endolysosomal system. The capsid and inner envelope are found in early endosomes or macropinosomes early after infection, colocalizing with EEA1 and Rab5, while at later times they co-localize with markers of late endosomes and lysosomes, such as Rab7 or Lamp 1. A direct relationship has been established between the maturity of the endosomal pathway and the progression of infection in the cell. Finally, ASFV uncoating first involves the loss of the outer capsid layers, and later fusion of the inner membrane with endosomes, releasing the nude core into the cytosol.

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“…Development of standardized and permissive cell lines that support replication of gene‐deleted ASFVs in a genetically stable manner is equally important; however, it remains a major gap in the development of ASF vaccines. Currently, a limited number of cell lines have been reported, and their applications in large scale to produce genetically stable live attenuated ASF vaccine in the context of different strains should be further explored (Sánchez et al, ). To achieve and advance the future live attenuated ASF vaccines, the priority research areas are summarized in Table .…”

Section: Future Perspectives and Recommendations: The Next‐generationmentioning

confidence: 99%

Current status and evolving approaches to African swine fever vaccine development

Teklue

Sun

Abid

et al. 2019

Transbound Emerg Dis

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African swine fever (ASF) is a highly lethal haemorrhagic disease of swine caused by African swine fever virus (ASFV), a unique and genetically complex virus. The disease continues to be a huge burden to the pig industry in Africa, Europe and recently in Asia, especially China. The purpose of this review was to recapitulate the current scenarios and evolving trends in ASF vaccine development. The unavailability of an applicable ASF vaccine is partly due to the complex nature of the virus, which encodes various proteins associated with immune evasion. Moreover, the incomplete understanding of immune protection determinants of ASFV hampers the rational vaccine design. Developing an effective ASF vaccine continues to be a challenging task due to many undefined features of ASFV immunobiology. Recent attempts on DNA and live attenuated ASF vaccines have been reported with promising efficacy, and especially live attenuated vaccines have been proved to provide complete homologous protection. Single‐cycle viral vaccines have been developed for various diseases such as Rift Valley fever and bluetongue, and the rational extension of these strategies could be helpful for developing single‐cycle ASF vaccines. Therefore, live attenuated vaccines in short term and single‐cycle vaccines in long term would be the next generation of ASF vaccines.

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Phenotyping and susceptibility of established porcine cells lines to African Swine Fever Virus infection and viral production

Cited by 45 publications

References 60 publications

Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages

Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages

Mechanisms of Entry and Endosomal Pathway of African Swine Fever Virus

Current status and evolving approaches to African swine fever vaccine development

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