Influence of pan-caspase inhibitors on coxsackievirus B3-infected CD19+ B lymphocytes

Abstract

Coxsackievirus B3 (CVB3), together with other enteroviruses of the picornavirus family, is associated with a wide variety of acute and chronic forms of human diseases. Using the murine model of CVB3-caused myocarditis, this pathogen can be detected not only in solid organs but also in different types of immune cells, preferentially in B lymphocytes. Therefore, these cells could represent a non-cardiac virus reservoir and may play an important role with regard to viral dissemination in the infected host. In addition, the infection of specific immune cells might modulate the severity of tissue injury and the pattern of virus-caused pathology in susceptible or resistant individuals. In the present study it could be demonstrated that CVB3 was capable to infect productively a certain percentage of murine CD19(+) B cells. In vivo studies revealed that CVB3 invaded murine CD19(+) B cells during an acute infection. Three days p. i. approximately 0.5-1.0% of these cells were productively infected. This proportion could be decreased up to 45%, if 3 days p. i. mice were intravenously treated with the pan-caspase inhibitors Z-VAD-FMK or Q-VD-OPH. These data were compared with results obtained from CVB3-infected human Raji cells.

Coxsackievirus B3 Infects the Bone Marrow and Diminishes the Restorative Capacity of Erythroid and Lymphoid Progenitors

“…Therefore, day 1 after infection may represent an eclipse state of the virus infection of BM cells, which transitions to productive infection only when the BM cells receive the appropriate external stimuli. In agreement with previous studies (54,62,63), we also identified productively infected PBMC, the frequency of which peaked on day 3 p.i., 24 h later than in the BM (Fig. 1C).…”

“…The BM is the primary repository, and source, of stem cells in the adult animal, so we considered it interesting to determine the effects of the virus on these cells and their immediate progeny. Second, CVB3 is known to infect a small proportion of B and T lymphocytes in the peripheral blood and spleen (51)(52)(53)(54). In adults, essentially all lymphocytic progenitors come from the BM, which is an important primary immune organ that also harbors CD8 ϩ effector and memory T cells (55); thus, we sought to characterize the impact of CVB3 infection on BM lymphocytes and their progenitors.…”

Primary neurons become less susceptible to coxsackievirus B5 following maturation: The correlation with the decreased level of CAR expression on cell surface

“…Although some has been reported that the pan-caspase inhibitor Z-VAD. fmk inhibits viral titers in vivo, we previously provided evidence that it does not induce antiviral effects against CVB in immature neurons [Ahn et al, 2004;DeBiasi et al, 2004;Jarasch et al, 2007]. Thus, a caspasedependent apoptosis does not seem to be a major determinant for viral permissiveness of neurons.…”

Characterization of Infections of Human Leukocytes by Non-Polio Enteroviruses

“…Previously, Vuorinen et al [1,6] and others [2][3][4] suggested that CVB3 in particular replicates well in the B-and T-cell line than in the monocyte cell line and PBMCs. Additionally, several studies provided evidence that B cells play a role in viral dissemination as a reservoir in CVB3 infection [5,[7][8][9] . However, which type(s) of leukocytes of B, T and monocyte cells are responsible for the spread of various non-polio EVs still needs to be further clarified.…”