Interaction of severe acute respiratory syndrome-associated coronavirus with dendritic cells

Abstract

Severe acute respiratory syndrome (SARS) of humans is caused by a novel coronavirus of zoonotic origin termed SARS-associated coronavirus (SARS-CoV). The virus induces severe injury of lung tissue, as well as lymphopenia and destruction of the architecture of lymphatic tissue by as-yet-unknown mechanisms. In this study, the interaction of SARS-CoV with dendritic cells (DCs), the key regulators of immune responses, was analysed. Monocyte-derived DCs were infected with SARS-CoV and analysed for viability, surface-marker expression and alpha interferon (IFN-a) induction. SARS-CoV infection was monitored by quantitative RT-PCR, immunofluorescence analysis and recovery experiments. SARS-CoV infected both immature and mature DCs, although replication efficiency was low. Immature DCs were activated by SARS-CoV infection and by UV-inactivated SARS-CoV. Infected DCs were still viable on day 6 post-infection, but major histocompatibility complex class I upregulation was missing, indicating that DC function was impaired. Additionally, SARS-CoV infection induced a delayed activation of IFN-a expression. Therefore, it is concluded that SARS-CoV has the ability to circumvent both the innate and the adaptive immune systems.

Role of Interferon Regulatory Factor 3 in Type I Interferon Responses in Rotavirus-Infected Dendritic Cells and Fibroblasts

“…It is also consistent with a role of virally encoded proteins in suppressing the type I IFN response, as UV treatment abolishes the ability of the viral RNA to replicate and to act as a template for protein production. We, and others, have previously shown that productive viral infection is not required for DC activation and type I IFN induction, since these can occur even in response to entrycompetent UV-inactivated virus but not in response to entrydeficient virus (29,70). The results obtained with the DLP-, TLP-, and UV-treated RRV preparations in this study are consistent with these results.…”

“…However, type I IFN also play a role in driving the generation of adaptive immune responses (45-49, 61, 65), a process during which dendritic cells (DCs) play a central role. Studies have shown that virus exposure stimulates DCs to upregulate the surface expression of costimulatory molecules (11,29,52,70) and that type I IFN are important for mediating this effect (30,31). Viruses that encode type I IFN antagonists may therefore induce suboptimal immune responses not only in the early phase of the infection but also in terms of longterm adaptive responses, as recently discussed for influenza virus and its type I IFN antagonist, nonstructural protein 1 (NS1) (19).…”

Reverse Genetics of SARS-Related Coronavirus Using Vaccinia Virus-Based Recombination

“…This suggests that the abortive infection is terminated prior to the expression of detectable levels of viral gene products. This result confirms and extends the previous work of Law et al and Spiegel et al [13], [14], [22]. The implication is that direct infection of hDCs by SARS-CoV may only marginally contribute to the induction of any cellular immune response, in contrast to HCoV-229E, which has been shown to efficiently stimulate CD8 + T cells following infection of hDCs [24].…”

“…Infection of hDCs with SARS-CoV has been shown to be abortive and replication is only barely detectable [13], [14], [22]. However, it is not known to what extent SARS-CoV gene expression can occur in hDCs.…”

“…At the same time, there was no evidence of virus production, nor did the cells exhibit cytopathic changes or signs of maturation [13]. Similarly, Spiegel et al reported that SARS-CoV can infect mdDC cells, however virus titres declined until six days post infection suggesting that SARS-CoV replication efficiency was very low [14].…”