African Swine Fever Virus MGF110-7L Induces Host Cell Translation Suppression and Stress Granule Formation by Activating the PERK/PKR-eIF2α Pathway

Han, Zhongchao; Fan, Shuai; Du, Yongkun; Zhang, Yuhang; Zhang, Angke; Jiang, Dawei; Han, Shichong; Wan, Bo; Zhang, Gaiping

doi:10.1128/spectrum.03282-22

Cited by 9 publications

(5 citation statements)

References 60 publications

(86 reference statements)

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“…The MGF110-7L is implicated in subverting the host protein synthesis machinery, inducing phosphorylation of eIF2α through protein kinase R (PKR) and PKR-like endoplasmic reticulum (ER) kinase (PERK). This process was found to be essential for host translation repression and stress granule (SG) formation [57]. Certain members of the MGF360 family have been identified as essential for replication in pigs, ticks, and macrophages [58][59][60][61][62][63][64].…”

Section: Discussionmentioning

confidence: 99%

A Deep Sequencing Strategy for Investigation of Virus Variants within African Swine Fever Virus-Infected Pigs

Johnston,

Olesen,

Lohse

et al. 2024

Pathogens

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African swine fever virus (ASFV) is the causative agent of African swine fever, an economically important disease of pigs, often with a high case fatality rate. ASFV has demonstrated low genetic diversity among isolates collected within Eurasia. To explore the influence of viral variants on clinical outcomes and infection dynamics in pigs experimentally infected with ASFV, we have designed a deep sequencing strategy. The variant analysis revealed unique SNPs at <10% frequency in several infected pigs as well as some SNPs that were found in more than one pig. In addition, a deletion of 10,487 bp (resulting in the complete loss of 21 genes) was present at a nearly 100% frequency in the ASFV DNA from one pig at position 6362-16849. This deletion was also found to be present at low levels in the virus inoculum and in two other infected pigs. The current methodology can be used for the currently circulating Eurasian ASFVs and also adapted to other ASFV strains and genotypes. Comprehensive deep sequencing is critical for following ASFV molecular evolution, especially for the identification of modifications that affect virus virulence.

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Section: Discussionmentioning

confidence: 99%

A Deep Sequencing Strategy for Investigation of Virus Variants within African Swine Fever Virus-Infected Pigs

Johnston,

Olesen,

Lohse

et al. 2024

Pathogens

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“…As shown in Table 3, 3 out of the 8 genes have been previously identifed as involving immune modulation of host responses. MGF 110-7L induces host cell translation suppression and stress granule formation by activating the PERK/PKR-eIF2 alpha pathway [57]. MGF360-10L has been implicated in the modulation of the type I interferon (IFN) response and associated with the virulence of the virus [58].…”

Section: Discussionmentioning

confidence: 99%

Tracing the Origin of Genotype II African Swine Fever Virus in China by Genomic Epidemiology Analysis

Zhang

Wang

Zhu

et al. 2023

Transboundary and Emerging Diseases

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The pandemic spread of African swine fever (ASF) has caused serious effects on the global pig industry. Virus genome sequencing and genomic epidemiology analysis play an important role in tracking the outbreaks of the disease and tracing the transmission of the virus. Here we obtained the full-length genome sequence of African swine fever virus (ASFV) in the first outbreak of ASF in China on August 3rd, 2018 and compared it with other published genotype II ASFV genomes including 9 genomes collected in China from September 2018 to October 2020. Phylogenetic analysis on genomic sequences revealed that genotype II ASFV has evolved into different genetic clusters with temporal and spatial correlation since being introduced into Europe and then Asia. There was a strong support for the monophyletic grouping of all the ASFV genome sequences from China and other Asian countries, which shared a common ancestor with those from the Central or Eastern Europe. An evolutionary rate of 1.312 × 10−5 nucleotide substitutions per site per year was estimated for genotype II ASFV genomes. Eight single nucleotide variations which located in MGF110-1L, MGF110-7L, MGF360-10L, MGF505-5R, MGF505-9R, K145R, NP419L, and I267L were identified as anchor mutations that defined genetic clusters of genotype II ASFV in Europe and Asia. This study expanded our knowledge of the molecular epidemiology of ASFV and provided valuable information for effective control of the disease.

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“…Interestingly, we found that the ASFV gene MGF110-7L was downregulated significantly in the transcriptome of ASFV-GS-Δ18R/NL/UK but not in that of ASFV-GS. ASFV MGF110-7L has been reported to trigger stress granule (SG) formation and inhibit host cell translation by inducing phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) ( 29 ). This process may play an important role in the virulence of ASFV in pigs.…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between the downregulation of MGF110-7L and three deleted genes remains unclear. Given that MGF110-7L and DP71L are found to be functionally linked to eIF2α ( 29 , 30 ), it is reasonable to speculate that altering one gene may have an impact on the other. In addition, these genes might have other, as-yet-unidentified, functions.…”

Section: Discussionmentioning

confidence: 99%

Deletion of DP148R , DP71L , and DP96R Attenuates African Swine Fever Virus, and the Mutant Strain Confers Complete Protection against Homologous Challenges in Pigs

Tian

et al. 2023

J Virol

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African Swine Fever Virus MGF110-7L Induces Host Cell Translation Suppression and Stress Granule Formation by Activating the PERK/PKR-eIF2α Pathway

Cited by 9 publications

References 60 publications

A Deep Sequencing Strategy for Investigation of Virus Variants within African Swine Fever Virus-Infected Pigs

A Deep Sequencing Strategy for Investigation of Virus Variants within African Swine Fever Virus-Infected Pigs

Tracing the Origin of Genotype II African Swine Fever Virus in China by Genomic Epidemiology Analysis

Deletion of DP148R , DP71L , and DP96R Attenuates African Swine Fever Virus, and the Mutant Strain Confers Complete Protection against Homologous Challenges in Pigs

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