African swine fever virus-cell interactions: From virus entry to cell survival

Alonso, Covadonga; Galindo, Inmaculada; Cuesta-Geijo, Miguel Ángel; Hernáez, Bruno; Muñoz-Moreno, Raquel

doi:10.1016/j.virusres.2012.12.006

Cited by 53 publications

(44 citation statements)

References 139 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ASFV vBCL2 strongly inhibits both autophagy (reviewed in ref. 898) and apoptosis. 899 HIV-1 utilizes the initial, nondegradative stages of autophagy to promote its replication in macrophages.…”

Section: O Vacuole Import and Degradation Pathwaymentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky¹,

Abdelmohsen²,

Abe³

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

Section: O Vacuole Import and Degradation Pathwaymentioning

confidence: 99%

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky¹,

Abdelmohsen²,

Abe³

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…and in swine. Indeed, ASFV replicates in the midgut epithelial cells of ticks at low pH values (24) and enters swine macrophages by a low-pH-dependent endocytic pathway (25). pA104R also binds DNA in an ATP-independent manner, suggesting that viral DNA packaging is a highly dynamic process, and a prompt DNA compaction may be critical to generate a high number of ASFV particles and to maintain a successful infection.…”

Section: Discussionmentioning

confidence: 99%

DNA-Binding Properties of African Swine Fever Virus pA104R, a Histone-Like Protein Involved in Viral Replication and Transcription

Frouco

Freitas

Coelho

et al. 2017

J Virol

View full text Add to dashboard Cite

African swine fever virus (ASFV) codes for a putative histone-like protein (pA104R) with extensive sequence homology to bacterial proteins that are implicated in genome replication and packaging. Functional characterization of purified recombinant pA104R revealed that it binds to single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) over a wide range of temperatures, pH values, and salt concentrations and in an ATP-independent manner, with an estimated binding site size of about 14 to 16 nucleotides. Using site-directed mutagenesis, the arginine located in pA104R's DNA-binding domain, at position 69, was found to be relevant for efficient DNA-binding activity. Together, pA104R and ASFV topoisomerase II (pP1192R) display DNA-supercoiling activity, although none of the proteins by themselves do, indicating that the two cooperate in this process. In ASFV-infected cells, A104R transcripts were detected from 2 h postinfection (hpi) onward, reaching a maximum concentration around 16 hpi. pA104R was detected from 12 hpi onward, localizing with viral DNA replication sites and being found exclusively in the Tritoninsoluble fraction. Small interfering RNA (siRNA) knockdown experiments revealed that pA104R plays a critical role in viral DNA replication and gene expression, with transfected cells showing lower viral progeny numbers (up to a reduction of 82.0%), lower copy numbers of viral genomes (Ϫ78.3%), and reduced transcription of a late viral gene (Ϫ47.6%). Taken together, our results strongly suggest that pA104R participates in the modulation of viral DNA topology, probably being involved in viral DNA replication, transcription, and packaging, emphasizing that ASFV mutants lacking the A104R gene could be used as a strategy to develop a vaccine against ASFV.IMPORTANCE Recently reintroduced in Europe, African swine fever virus (ASFV) causes a fatal disease in domestic pigs, causing high economic losses in affected countries, as no vaccine or treatment is currently available. Remarkably, ASFV is the only known mammalian virus that putatively codes for a histone-like protein (pA104R) that shares extensive sequence homology with bacterial histone-like proteins. In this study, we characterized the DNA-binding properties of pA104R, analyzed the functional importance of two conserved residues, and showed that pA104R and ASFV topoisomerase II cooperate and display DNA-supercoiling activity. Moreover, pA104R is expressed during the late phase of infection and accumulates in viral DNA replication sites, and its downregulation revealed that pA104R is required for viral DNA replication and transcription. These results suggest that pA104R participates in the modulation of viral DNA topology and genome packaging, indicating that A104R deletion mutants may be a good strategy for vaccine development against ASFV.

show abstract

“…ASFV replication organelle or viral factory (VF) is a single structure lacking an outer limiting membrane in a cytoplasmic location near the nucleus at the MTOC [7]. Fully-formed ASFV VF is surrounded by mitochondria [33,34] and a vimentin cage [35].…”

Section: Discussionmentioning

confidence: 99%

Redistribution of Endosomal Membranes to the African Swine Fever Virus Replication Site

Cuesta-Geijo

Barrado-Gil

Galindo

et al. 2017

Viruses

Self Cite

View full text Add to dashboard Cite

African swine fever virus (ASFV) infection causes endosomal reorganization. Here, we show that the virus causes endosomal congregation close to the nucleus as the infection progresses, which is necessary to build a compact viral replication organelle. ASFV enters the cell by the endosomal pathway and reaches multivesicular late endosomes. Upon uncoating and fusion, the virus should exit to the cytosol to start replication. ASFV remodels endosomal traffic and redistributes endosomal membranes to the viral replication site. Virus replication also depends on endosomal membrane phosphoinositides (PtdIns) synthesized by PIKfyve. Endosomes could act as platforms providing membranes and PtdIns, necessary for ASFV replication. Our study has revealed that ASFV reorganizes endosome dynamics, in order to ensure a productive infection.

show abstract

African swine fever virus-cell interactions: From virus entry to cell survival

Cited by 53 publications

References 139 publications

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

DNA-Binding Properties of African Swine Fever Virus pA104R, a Histone-Like Protein Involved in Viral Replication and Transcription

Redistribution of Endosomal Membranes to the African Swine Fever Virus Replication Site

Contact Info

Product

Resources

About