Infectious Bursal Disease Virus Changes the Potassium Current Properties of Chicken Embryo Fibroblasts

Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University, Giessen, Germany.
Virology (Impact Factor: 3.32). 08/1998; 246(2):362-9. DOI: 10.1006/viro.1998.9187
Source: PubMed


Infectious bursal disease virus (IBDV) is the causative agent of an economically significant poultry disease. IBDV infection leads to apoptosis in chicken embryos and cell cultures. Since changes in cellular ion fluxes during apoptosis have been reported, we investigated the membrane ion currents of chicken embryo fibroblasts (CEFs) inoculated with the Cu-1 strain of IBDV using the patch-clamp recording technique. Incubation of CEFs with IBDV led to marked changes in their K+ outward current properties, with respect to both the kinetics of activation and inactivation and the Ca2+ dependence of the activation. The changes occurred in a time-dependent manner and were complete after 8 h. UV-treated noninfectious virions induced the same K+ current changes as live IBDV. When CEFs were inoculated with IBDV after pretreatment with a neutralizing antibody, about 30% of the cells showed a normal K+ current, whereas the rest exhibited K+ current properties identical to or closely resembling those of IBDV-infected cells. Incubation of CEFs with culture supernatant from IBDV-infected cells from which the virus particles were removed had no influence on the K+ current. Our data strongly suggest that the K+ current changes induced by IBDV are not due to virus replication, but are the result of attachment and/or membrane penetration. Possibly, the altered K+ current may delay the apoptotic process in CEFs after IBDV infection.

Download full-text


Available from: Henning J Draheim,
22 Reads
  • Source
    • "Results of other investigations may indicate that the IBDV attachment molecule is composed of an N-glycosylated protein (Ogawa et al., 1998). As known for several other viruses, IBDV infection also changes the potassium current properties of chicken embryo fibroblasts (Repp et al., 1998). These might cause alterations of membrane permeability, thus affecting intracellular ion homeostasis and contributing to cytolysis and the death of the infected cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Infectious bursal disease (IBD) virus (IBDV) is the etiological agent of "Gumboro disease". Although first observed about 40 years ago, this disease continues to pose an important threat to the commercial poultry industry. The emergence of antigenic variant as well as very virulent strains in vaccinated flocks considerably stimulated research efforts on both, IBD and IBDV. In this review, some of the recent advances in the understanding of the structure, morphogenesis and molecular biology of the virus as well as in development of new diagnostic approaches and new strategies for vaccination against IBD are briefly summarized.
    Veterinary Microbiology 12/2003; 97(1-2):153-65. DOI:10.1016/j.vetmic.2003.08.005 · 2.51 Impact Factor
  • Source
    • "Infectious bursal disease virus (IBDV), a member of the family Birnaviridae, induced apoptosis in chicken peripheral lymphocytes and embryo fibroblasts. IBDV incubation of several hours eliminated the inactivation of an outward delayed rectifier K + current and accelerated the opening phase of the current (Repp et al., 1998). The changes lasted for many hours, allowing a significant K + efflux. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Programmed cell death or apoptosis is broadly responsible for the normal homeostatic removal of cells and has been increasingly implicated in mediating pathological cell loss in many disease states. As the molecular mechanisms of apoptosis have been extensively investigated a critical role for ionic homeostasis in apoptosis has been recently endorsed. In contrast to the ionic mechanism of necrosis that involves Ca(2+) influx and intracellular Ca(2+) accumulation, compelling evidence now indicates that excessive K(+) efflux and intracellular K(+) depletion are key early steps in apoptosis. Physiological concentration of intracellular K(+) acts as a repressor of apoptotic effectors. A huge loss of cellular K(+), likely a common event in apoptosis of many cell types, may serve as a disaster signal allowing the execution of the suicide program by activating key events in the apoptotic cascade including caspase cleavage, cytochrome c release, and endonuclease activation. The pro-apoptotic disruption of K(+) homeostasis can be mediated by over-activated K(+) channels or ionotropic glutamate receptor channels, and most likely, accompanied by reduced K(+) uptake due to dysfunction of Na(+), K(+)-ATPase. Recent studies indicate that, in addition to the K(+) channels in the plasma membrane, mitochondrial K(+) channels and K(+) homeostasis also play important roles in apoptosis. Investigations on the K(+) regulation of apoptosis have provided a more comprehensive understanding of the apoptotic mechanism and may afford novel therapeutic strategies for apoptosis-related diseases.
    Progress in Neurobiology 08/2003; 70(4):363-86. DOI:10.1016/S0301-0082(03)00090-X · 9.99 Impact Factor
  • Source
    • "The lurcher gene-induced apoptosis in cerebellar Purkinje cells follows expression of Kv3.3 channels , implying a role for these K ϩ channels (Norman et al., 1995). Infection of chicken embryo fibroblasts with infectious bursal disease virus blocks inactivation of outward K ϩ currents, i.e., more K ϩ efflux, and is followed several hours later by apoptotic death (Repp et al., 1998). On the other hand, the apoptotic proteins Reaper and Grim induce inactivation of K ϩ currents; the authors suggested that Reaper and Grim may initiate apoptosis by blocking K ϩ channels (Avdonin et al., 1998). "
    [Show abstract] [Hide abstract]
    ABSTRACT: We studied the novel hypothesis that an up-modulation of channels for outward delayed rectifier K+ current (I(K)) plays a key role in ceramide-induced neuronal apoptosis. Exposure for 6-10 h to the membrane-permeable C2-ceramide (25 microM) or to sphingomyelinase (0.2 unit/ml), but not to the inactive ceramide analogue C2-dihydroceramide (25 microM), enhanced the whole-cell I(K) current without affecting the transient A-type K+ current and increased caspase activity, followed by neuronal apoptosis 24 h after exposure onset. Tetraethylammonium (TEA) or 4-chloro-N,N-diethyl-N-heptylbenzenebutanaminium tosylate (clofilium), at concentrations inhibiting I(K), attenuated the C2-ceramide-induced caspase-3-like activation as well as neuronal apoptosis. Raising extracellular K+ to 25 mM similarly blocked the C2-ceramide-induced cell death; the neuroprotection by 25 mM K+ or TEA was not eliminated by blocking voltage-gated Ca2+ channels. An inhibitor of tyrosine kinases, herbimycin A (10 nM) or lavendustin A (0.1-1 microM), suppressed I(K) enhancement and/or apoptosis induced by C2-ceramide. It is suggested that ceramide-induced I(K) current enhancement is mediated by tyrosine phosphorylation and plays a critical role in neuronal apoptosis.
    Journal of Neurochemistry 10/1999; 73(3):933-41. · 4.28 Impact Factor
Show more