Herpes Simplex Virus Infection of Dendritic Cells: Balance among Activation, Inhibition, and Immunity

Abstract

Several lines of evidence suggest that dendritic cells (DCs),Herpes simplex virus (HSV) belongs to the Herpesviridiae family, which have the characteristic ability to establish latency after primary infection, and thus to persist in the human host for life. For a virus to do so, it must be able to avoid immune eradication both after primary infection and after subsequent reactivation.Although the importance of innate immunity in HSV infection has been well characterized [1], it is the degree of adaptive immunity that best correlates with the severity of consequent clinical disease. Cellular immune

Frontline: Induction of apoptosis and modulation of c‐FLIPL and p53 in immature dendritic cells infected with herpes simplex virus

“…This is in accordance with a recent report showing that roughly 80% of immature DC stain positive for HSV antigens after infection with HSV [15]. Thus, HSV efficiently infects immature DC as also shown by previous studies [10,11,[13][14][15]. Using annexin V staining and TUNEL assay, we observed that a significant percentage of immature DC undergo apoptosis after HSV infection.…”

“…Similarly, it has been shown that CD95 ligation can activate DC [21]. Thus c-FLIP L might be involved in maturation of DC and its down-regulation could contribute to the activation block observed after HSV infection [11,[13][14][15]. In accordance with this idea we observed that LPS, a strong stimulus of DC activation, did not abrogate HSVinduced down-regulation of c-FLIP L in immature DC.…”

“…Using annexin V staining and TUNEL assay, we observed that a significant percentage of immature DC undergo apoptosis after HSV infection. Recently, reduced viability of immature DC after HSV infection in assays using Trypan blue exclusion or overall metabolic activity has been reported [13,14] and enhanced DNA degradation after HSV infection was detected by PI staining of ethanol-fixed DC [14].…”

“…[10][11][12][13][14][15]. Intriguingly, production of infectious virus was associated with progressive loss of infected DC [13,14]. However, the underlying mechanisms of HSV-induced apoptosis in DC remain to be defined.…”

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

“…Most studies demonstrated that HSV-1 infects immature DCs efficiently, resulting in effects such as incomplete maturation, inadequate induction of T-cell responses or delayed apoptosis (Björck, 2004;Galvan & Roizman, 1998;Mikloska et al, 2001;Müller et al, 2004;Pollara et al, 2003). In addition, when immature DCs were infected efficiently with HSV-1 (>90 % EGFP-positive cells), we saw a dramatic effect on maturation, in the form of reduced CCR7 and CXCR4 expression, and reduced chemokine-mediated migration was observed.…”