African swine fever virus evasion of host defences

Dixon, Linda K.; Islam, Muneeb; Nash, Rachel; Reis, Ana Luísa

doi:10.1016/j.virusres.2019.04.002

Cited by 144 publications

(157 citation statements)

References 107 publications

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“…The MGF groups were predicted to have large structural and functional diversity in our study. This may be related to the diverse functions of MGF proteins reported in previous studies (L. Dixon, Islam, Nash, & Reis, 2019; Netherton et al, 2019).…”

Section: Discussionsupporting

confidence: 58%

Classification of multigene families of African swine fever viruses

Zhu

Chen

Cao

et al. 2020

Preprint

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16 African swine fever virus (ASFV) is a large and complex double-stranded DNA virus 17 that poses serious threats to the pig industry. It is well-accepted that the multigene 18 family (MGF) proteins are extensively distributed in ASFVs and are generally 19 classified into five families, including MGF-100, MGF-110, MGF-300, MGF-360 and 20 MGF-505. Most MGF proteins, however, have not been well characterized and 21 classified within each family. To bridge this gap, this study first classified the MGF 22

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Section: Discussionsupporting

confidence: 58%

Classification of multigene families of African swine fever viruses

Zhu

Chen

Cao

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…At early time post infection (2 h pi), neither virulent nor attenuated ASFV strains affected moMΦ cytokine responses to classical activation (IFN-γ and LPS) (data not shown), suggesting that the synthesis of ASFV viral proteins is required to inhibit macrophage response to external stimuli. ASFV encodes several proteins involved in evasion of host defenses [24], including A238L that inhibits inflammatory responses through NF-kB regulation [24], and this might result in reduced ability to respond to external stimuli. In addition, NH/P68 presented a more pronounced inhibitory effect compared to 22653/14, and this might be linked to its higher replication efficacy early time pi.…”

Section: Discussionmentioning

confidence: 99%

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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“…We ascertain the genetic properties of the genes with positive diversifying selection or selective sweep by calculating population prevalence frequencies and pair-wise amino acid divergence of the genes and doing comparison with three gene categories cataloged from other studies: (i) the non-antigenic conserved structural proteins without positive selection (32), (ii) the antigen proteins eliciting immunological responses in immunoassay experiments (40)(41)(42), (iii) the proteins previously shown to be involved in host cell interactions (10,43) ( Figure 4 and Table S6). A non-uniform population prevalence and higher level of sequence variability are observed in the candidate genes under putative positive diversifying selection in comparison with the category of (i) conserved structural proteins and (ii) antigenic proteins, but not with the gene category (iii) involved in host cell interactions (two-sided Mann-Whitney U-test, Figure 4a…”

Section: Sequence Variability Of the Candidate Genes With Diversifyinmentioning

confidence: 99%

The genetic variation landscape of African swine fever virus reveals frequent positive selection and adaptive flexibility

Bao

Qiu

Luo

et al. 2020

Preprint

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African swine fever virus (ASFV) is a lethal disease agent that causes high mortality in swine population and devastating loss in swine industries. The development of efficacious vaccines has been hindered by the knowledge gap in genetic properties of ASFV and the interface of virus-host interactions. In this study, we performed a genetic study of ASFV aiming to profile the variation landscape and identify genetic factors with signatures of positive selection and relevance to virus-host interactions. To achieve this goal, we developed a new tool "SweepCluster" for systematic identification of selective sweep. Our data reveals a high level of genetic variability of ASFV shaped by both diversifying selection and selective sweep. The selection signatures are widely distributed across the genome with the diversifying selection falling within 29 genes and selection sweep within 25 genes. Further examination of the structure properties reveals the link of the selection signatures with virus-host interactions. Specifically, we discovered a site at 157th of the antigen protein EP402R under diversifying selection located in the cytotoxic T-cell epitope involved in the serotype-specific T-cell response. Moreover, we reported 24 novel candidate genes with relevance to virus-host interactions. By integrating the candidate genes with selection signatures into a unified framework of interactions between ASFV and hosts, we showed that those genes are involved in multiple processes of host immune evasion and virus life cycles, and may play crucial roles in circumventing host defense systems and enhancing adaptive fitness.

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African swine fever virus evasion of host defences

Cited by 144 publications

References 107 publications

Classification of multigene families of African swine fever viruses

Classification of multigene families of African swine fever viruses

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

The genetic variation landscape of African swine fever virus reveals frequent positive selection and adaptive flexibility

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