Viruses have evolved multiple mechanisms to evade the innate immune response, particularly the actions of interferons (IFNs). We have previously reported that exposure of dendritic cells (DCs) to foot-and-mouth disease virus (FMDV) in vitro yields no infection and induces a strong type I IFN (IFN-alpha and IFN-beta) response, indicating that DCs may play a critical role in the innate response to the virus. In vivo, FMDV induces lymphopenia and reduced T-cell proliferative responses to mitogen, viral effects that may contribute to evasion of early immune responses. In this study we analyzed the in vivo effects of FMDV infection on the IFN-alpha response of two populations of dendritic cells. During the acute phase of infection of swine, production of IFN-alpha from monocyte-derived DCs (MoDCs) and skin-derived DCs (skin DCs) is inhibited. This effect occurs concurrently with rising viral titers in the blood; however, these cells are not productively infected. Interestingly, there are no changes in the capability of these DCs to take up particles and process antigens, indicating that antigen-presenting cell function is normal. These data indicate that inhibition of the IFN-alpha response of dendritic cell populations from blood and skin by FMDV enhances viral pathogenesis in infected animals.
-Inoculation of vesicular stomatitis New Jersey virus (VSNJV) by skin scarification of the coronary-band in cattle, a natural host of VSNJV, resulted in vesicular lesions and 6−8 log 10 TCID 50 increase in skin virus titers over a 72 h period. Virus infection was restricted to the lesion sites and lymph nodes draining those areas but no virus or viral RNA was found in the blood or in 20 other organs and tissues sampled at necropsy. Scarification of flank skin did not result in lesions or a significant increase in viral titer indicating that viral clinical infection is restricted to skin inoculation at sites where lesions naturally occur. Viral antigens co-localized primarily with keratinocytes in the coronary band, suggesting these cells are the primary site of viral replication. Viral antigen also co-localized with few MHC-II positive cells, but no co-localization was observed in cells positive for macrophage markers. Although granulocyte infiltration was observed in lesions, little viral antigen co-localized with these cells. This is the first detailed description of VSNJV tissue distribution and infected cell characterization in a natural host. The pathogenesis model shown herein could be useful for in-vivo tracking of virus infection and local immune responses. vesicular stomatitis / bovine / pathogenesis / confocal microscopy / keratinocytes
Abstract. The role of interdigitating dendritic cells (IDCs) in the early pathogenesis of African swine fever (ASF) was investigated using mandibular lymphoid tissue from normal pigs and pigs inoculated oronasally with highly virulent Lisbon 60 (L-60) and moderately virulent Dominican Republic 1979 (DR-2) ASF virus (ASFV) isolates. Paraffin-embedded tissue sections were immunostained for ASFV antigen and S-100 protein, a marker of IDCs, using an avidin-biotin alkaline phosphatase procedure. Swine IDCs were identified morphologically by light microscopy, electron microscopy, and S-100 immunostaining. Infection with ASFV caused a marked reduction in S-100 staining by 3 days postinfection (DPI) that persisted through 14 DPI. Early ASFV infection of IDCs was demonstrated at 3 DPI by double immunohistochemical staining of cryosections and by transmission electron microscopy. These results support the hypothesis that the failure of a humoral immune response to virulent ASFV may be due to a primary infection of IDCs and the inability of IDCs to initiate an immune response. Infection of IDCs has also been demonstrated with human immunodeficiency virus (HIV-1), and these infections have some aspects in common.
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