Biomaterial Database

Host DNA damage response facilitates African swine fever virus infection. 2013

Margarida Simões, and Carlos Martins, and Fernando Ferreira

CIISA, Departamento de Sanidade Animal, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Alto da Ajuda, 1300-477 Lisboa, Portugal.

Studies with different viral infection models on virus interactions with the host cell nucleus have opened new perspectives on our understanding of the molecular basis of these interactions in African swine fever virus (ASFV) infection. The present study aims to characterize the host DNA damage response (DDR) occurring upon in vitro infection with the ASFV-Ba71V isolate. We evaluated protein levels during ASFV time-course infection, of several signalling cascade factors belonging to DDR pathways involved in double strand break repair - Ataxia Telangiectasia Mutated (ATM), ATM-Rad 3 related (ATR) and DNA dependent protein kinase catalytic subunit (DNA-PKcs). DDR inhibitory trials using caffeine and wortmannin and ATR inducible-expression cell lines were used to confirm specific pathway activation during viral infection. Our results show that ASFV specifically elicits ATR-mediated pathway activation from the early phase of infection with increased levels of H2AX, RPA32, p53, ATR and Chk1 phosphorylated forms. Viral p72 synthesis was abrogated by ATR kinase inhibitors and also in ATR-kd cells. Furthermore, a reduction of viral progeny was identified in these cells when compared to the outcome of infection in ATR-wt. Overall, our results strongly suggest that the ATR pathway plays an essential role for successful ASFV infection of host cells.

UI	MeSH Term	Description	Entries
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D002522	Chlorocebus aethiops	A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.	African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D000357	African Swine Fever	A sometimes fatal ASFIVIRUS infection of pigs, characterized by fever, cough, diarrhea, hemorrhagic lymph nodes, and edema of the gallbladder. It is transmitted between domestic swine by direct contact, ingestion of infected meat, or fomites, or mechanically by biting flies or soft ticks (genus Ornithodoros).	Swine Fever, African,African Swine Fever Virus Infection,Asfivirus Infection,Wart-Hog Disease,Asfivirus Infections,Infection, Asfivirus,Infections, Asfivirus,Wart Hog Disease,Wart-Hog Diseases
D000358	African Swine Fever Virus	The lone species of the genus Asfivirus. It infects domestic and wild pigs, warthogs, and bushpigs. Disease is endemic in domestic swine in many African countries and Sardinia. Soft ticks of the genus Ornithodoros are also infected and act as vectors.	Wart-Hog Disease Virus,Virus, Wart-Hog Disease,Wart Hog Disease Virus
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013552	Swine	Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).	Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D014709	Vero Cells	A CELL LINE derived from the kidney of the African green (vervet) monkey, (CHLOROCEBUS AETHIOPS) used primarily in virus replication studies and plaque assays.	Cell, Vero,Cells, Vero,Vero Cell
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051747	DNA-Activated Protein Kinase	A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.	DNA-Dependent Protein Kinase,DNA-Dependent Protein Serine-Threonine Kinase,DNA Activated Protein Kinase,DNA Dependent Protein Kinase,DNA Dependent Protein Serine Threonine Kinase,Kinase, DNA-Activated Protein,Kinase, DNA-Dependent Protein,Protein Kinase, DNA-Activated,Protein Kinase, DNA-Dependent