Classical swine fever (CSF) is a devastating disease, which is responsible for substantial economic losses due to the death of valuable livestock. For this reason, classical swine fever virus (CSFV), the causative agent of CSF, is a listed disease by the World Organisation for Animal Health [1, 2]. Since the implementation of strict immunization measures, changes have been reported in the epidemiological form and clinical signs of CSF. Large-scale outbreaks are now rare, but sporadic epizootics still occur frequently with chronic, atypical forms of the disease. Abortions, stillbirths, mummifications, malformations, and the birth of weak piglets have also been observed . Although some countries, such as Australia and Japan, have succeeded in eradicating the disease, CSF is still epidemic or endemic in many countries in Europe and Asia, including China .
CSFV is a single positive strand RNA virus of the genus Pestivirus in the family Flaviviridae, approximately 12.3 kilobases (kb) in length [5–8]. The virus has been detected in semen, gonads, tonsils, and lymph nodes, even in vaccinated pigs [9, 10]. It has been shown to evade the host immune system and to establish chronic infection under both natural and experimental conditions . Specifically for CSFV infection, host anti-viral Type I IFN, such as alpha-interferon (IFN-α), was suppressed in infected dendritic cells, and some other host cytokines including interleukin (IL)-6, IL-10, IL-12, and TNF-α were also not induced . There was an initial, short-lived increase in the transcription level of genes encoding for pro-inflammatory cytokines IL-1, IL-6, and IL-8 at 3 h, followed by a second, more sustained, increase at 24 h post CSFV infection . Transcription levels for genes encoding for coagulation factors, tissue factors, and vascular endothelial cell growth factor (VEGF), all of which are involved in endothelial cell permeability, were also increased . Sánchez-Cordón also reported that CSFV strain Alfort/187 from a Swiss isolate induced a change in cytokine expression (IL-2, IL-4, and IFN-γ) by the T-lymphocyte population (CD3+, CD4+, and CD8+) in serum, thymus and spleen.
In 2001, two independent studies confirmed that non-cytopathic bovine viral diarrhea virus (BVDV) can establish persistent infection by inhibiting the induction of type I interferon in vitro and in vivo[14, 15]. However, in addition to evading the immune response by altering cell surface markers and cytokine induction, many viruses have developed the ability to infect immune cells -- a strategy which plays a key role in orchestrating the inhibition of antiviral immune responses. For example, the HIV-1 virus infects CD4+ T cells, and the depletion of these cells is a hallmark of HIV-induced AIDS. Previous studies have demonstrated that CSFV has a particular affinity for cells of the immune system, and can compromise the host immune response. During CSF, both B- and T-lymphocytes are depleted [16–18]. CD4+ and CD8high+ T- lymphocyte levels drop dramatically before the onset of viremia [19, 20]. In addition, CSFV infection can suppress the function of T-lymphocytes isolated from CSFV-infected pigs [21, 22]. CSFV exhibits an especially high affinity for phagocytes of the macrophage and monocyte lineage (reticulo-endothelial cells), mostly in the vascular endothelium [23, 24]. Infection of these cells in the endothelium leads to an increase in vascular permeability, lymphopenia, thrombocytopenia, coagulation disorders, and atrophy of the thymus and bone marrow [25–27]. During the later stages of CSFV infection, peripheral monocytes, lymphocytes, and granulocytes can also carry viral antigens [28, 29]. Further studies have revealed that CSFV induces apoptosis in lymphocytes and in neutrophil-lineage cells of the bone marrow [30–33].
Studies of the interactions between hosts and specific viruses are critical for understanding pathogenic mechanisms and the immune response to infection. CSFV shows a predilection for cells of the immune system and may alter transcription of immune response genes. The global transcriptional profiles of peripheral blood mononuclear cells during CSFV infection have shown that cellular genes present a low level of up- and down-regulation in vivo. In order to gain more insight into the mechanisms of how CSFV affects host genes associated with immune response, we have investigated in vitro the activity of cellular genes in response to CSFV infection using the real-time RT-PCR.