| Popis: |
Kunjin virus (KUNV) is an Australian Flavivirus that very rarely causes disease in humans. West Nile virus (WNV) infects the central nervous system and causes severe disease primarily in humans. KUNV shares a high degree of homology and pathogenesis with WNV. Dendritic cells (DCs) are the professional antigen-presenting cells that play a fundamental role in both innate and adaptive immune responses against virus infection. By using different techniques, including flow cytometry analysis, viral plaque assay, and interferon (IFN) antiviral bioassay, this study demonstrates that KUNV can infect human immature monocyte-derived dendritic cells (MDDCs). KUNV RNA transiently replicated in human MDDCs and produced low titers of infectious virus particles. Exposure to live KUNV induced maturation and activation of both infected, and uninfected neighboring MDDCs. KUNV infection stimulated upregulation of the expression of DC maturation markers such as CD83, CD80, CD86 and HLA-DR. In contrast, both UV- inactivated and replication-defective KUNV failed to induce MDDC maturation. In addition, infection of human MDDCs with KUNV induces production of large amounts of type I IFN while the UV-inactivated and replication-defective viruses did not. The infection efficiency of immature MDDCs by different KUNV isolates indicated that there were no significant differences between KUNVs isolated directly from humans or from mosquitoes. The results suggest that limited viral RNA replication resulted in the production of type I interferons (IFNs) in the early stage of virus infection, which inhibited virus replication and spread in MDDC cultures. These results will lead to greater understanding of KUNV infection, and may be applicable to further development of a KUNV-based WNV vaccine and of KUN-replicon-based vaccine vectors. |
