The African swine fever virus dynein‐binding protein p54 induces infected cell apoptosis

Abstract

A specific interaction of ASFV p54 protein with 8 kDa light chain cytoplasmic dynein (DLC8) has been previously characterized and this interaction is critical during virus internalization and transport to factory sites. During early phases of infection, the virus induces the initiation of apoptosis triggering activation of caspase-9 and -3. To analyze the role of the structural protein p54 in apoptosis, transient expression experiments of p54 in Vero cells were carried out which resulted in effector caspase-3 activation and apoptosis. Interestingly, p54 mutants, lacking the 13 aa dynein-binding motif lose caspase activation ability and pro-death function of p54. This is the first reported ASFV protein which induces apoptosis.

African Swine Fever Virus

“…Caspase activation did not require viral DNA replication and protein synthesis, suggesting that induction of apoptosis in these cells is a very early event, perhaps involving ASFV uncoating Hernaez et al 2004). Interestingly, p54, the essential attachment, dynein-binding, and morphogenesis protein induced caspase-3 activation and apoptosis when transfected into cells ).…”

“…Apoptosis and activation of caspase-9 and -3, cysteine proteinases central to the apoptotic regulatory cascade, were observed in Vero cells early after inoculation with infectious but not UV-inactivated ASFV Hernaez et al 2004). Caspase activation did not require viral DNA replication and protein synthesis, suggesting that induction of apoptosis in these cells is a very early event, perhaps involving ASFV uncoating Hernaez et al 2004).…”

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

“…Cell death regulation by ASFV (Fig. 7) is a complex equilibrium between induction and inhibition signals (Reviewed in Hernaez et al, 2004). Although the execution of apoptosis in the target cell is a relatively late event, the signal triggering this process has been reported to occur early after virus interaction with the host cell.…”

Phenotype-Based Identification of Host Genes Required for Replication of African Swine Fever Virus

“…The observed effects of BAT3, which produces 25 different transcripts and putatively a large number of protein isoforms as a result of alternative splicing (39), on ASFV infection are of special interest, as there is considerable evidence that host cell apoptotic processes are perturbed during such infection (42; for review, see reference 69). However, this perturbation appears to be complex: proapoptotic proteins of host cells are increased during ASFV infection (26) and a virus-encoded protein(s) has been reported to induce host cell apoptosis soon after viral entry (13,28,29). Conversely, ASFV proteins also have been reported to interfere with apoptosis and specifically to limit synthesis of the stress-induced proapoptotic transcription factor CHOP/Gadd153 (40).…”