Induction of immature dendritic cell apoptosis by foot and mouth disease virus is an integrin receptor mediated event before viral infection

Abstract

Foot and mouth disease virus (FMDV) has been demonstrated to infect dendritic cells (DC) and reduced its ability to stimulate host immune responses. This study aimed to determine whether non-replicating FMDV could induce apoptosis of the host immune cells. In this study, we have demonstrated that bone morrow derived dendritic cells (BMDCs) were induced to undergo apoptosis in a dose-dependent manner, which was determined by the annexin-V staining, DNA fragmentation, and TUNEL staining methods, after they were treated with the chemically inactivated FMDV in vitro. The initiation of apoptosis was apparently via an interaction of the integrin receptor on BMDCs and the RGD motif within the VP1 capsid protein of FMDV. The initiation activated a cascade of apoptotic pathway including reduced expression of Bcl-2, activation of caspases, and release of cytochrome c from mitochondria. Pretreatment with BMDCs with LPS prevented the inactivated FMDV induced apoptosis, suggesting immature BMDCs are susceptible to such apoptosis. Taken together, the data demonstrate that the inactivated FMDV induces the apoptosis in BMDCs via the integrin receptor and subsequently triggers the apoptosis signal, suggesting that such induction of apoptosis is likely to impair immune responses against FMDV infection.

Dendritic Cell Apoptosis: Regulation of Tolerance versus Immunity

“…MV-pulsed human mDC-T cell cultures show enhanced rates of DC apoptosis along with an impairment of remaining viable DCs to induce T cell proliferation and undergo maturation (30). Other viruses, such as foot and mouth disease virus, have also been shown to induce apoptosis of murine immature mDCs (31). Brugia malayi, a nematode and causative agent of lymphatic filariasis (elephantiasis), promotes T cell hyporesponsiveness and induces human mDC apoptosis through TRAIL pathway, raising the possibility that T cell hyporesponsiveness may be a consequence of DC apoptosis (32).…”

Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral “Security” Protein

“…Collectively, these alterations pointed to the involvement of a mitochondrion-dependent, cytochrome c-dependent, and caspase-dependent apoptotic pathway(s). Picornaviruses are known to activate apoptotic pathways through interaction with plasma membrane receptors or intracellular sensors (8,15,53,102). Viral capsid proteins were implicated in triggering apoptosis both from without (9,53,76) and from within the cell (47,62).…”

“…Picornaviruses are known to activate apoptotic pathways through interaction with plasma membrane receptors or intracellular sensors (8,15,53,102). Viral capsid proteins were implicated in triggering apoptosis both from without (9,53,76) and from within the cell (47,62). Other possible players are viral proteases 3C and 2A (18,26,42,60,105) and viral nonstructural proteins 2B, 3A (64), and 2C (63).…”

“…Since then, a wealth of data has been accumulated that shows that the activation of apoptotic pathways is a widespread, though not universal, response to picornavirus infection. Thus, apoptosis-inducing capacity was reported for coxsackieviruses B3, B4, and B5 (22,54,82), enteroviruses 70 and 71 (25,27,60,88), human rhinoviruses 1B, 9, 14, and 16 (32,92,100), foot-and-mouth disease virus (53,76), avian encephalomyelitis virus (62,63), and hepatitis A virus (16,43) and was the subject of several recent reviews (15,102). The antiapoptotic activity of picornaviruses was studied predominantly by using poliovirus (3,8,13,72) and coxsackievirus B3 (21,36,85).…”

Interactions between Viral and Prokaryotic Pathogens in a Mixed Infection with Cardiovirus and Mycoplasma

“…A variety of mechanisms operating during distinct steps of viral reproduction have been implicated, but the relevant differences between various picornavirus representatives attracted relatively little attention. Now that we know how diverse are the mechanisms used by various picornaviruses to affect the translation of host mRNA (34,35,48,59,78,95), impair nucleocytoplasmic transport (6,9,10,25,36,37,50,64,65), suppress innate immunity (7,26,32,38,62,68,83,91), or affect the apoptotic machinery of the target cells (5,11,15,40,44,54,69,73,75,86), we should not be surprised by the possible variability of the viral effects on plasma membrane integrity. The relevant data are, however, rather scarce.…”