Ross River virus envelope glycans contribute to type I interferon production in myeloid dendritic cells.

Alphaviruses are mosquito-transmitted viruses that cause significant human disease, and understanding how these pathogens successfully transition from the mosquito vector to the vertebrate host is an important area of research. Previous studies demonstrated that mosquito and mammalian-cell-derived alphaviruses differentially induce type I interferons (alpha/beta interferon [IFN-alpha/beta]) in myeloid dendritic cells (mDCs), where the mosquito cell-derived virus is a poor inducer of IFN-alpha/beta compared to the mammalian-cell-derived virus. Furthermore, the reduced IFN-alpha/beta induction by the mosquito cell-derived virus is attributed to differential N-linked glycosylation. To further evaluate the role of viral envelope glycans in regulating the IFN-alpha/beta response, studies were performed to assess whether the mosquito cell-derived virus actively inhibits IFN-alpha/beta induction or is simply a poor inducer of IFN-alpha/beta. Coinfection studies using mammalian- and mosquito cell-derived Ross River virus (mam-RRV and mos-RRV, respectively) indicated that mos-RRV was unable to suppress IFN-alpha/beta induction by mam-RRV in mDC cultures. Additionally, a panel of mutant viruses lacking either individual or multiple N-linked glycosylation sites was used to demonstrate that N-linked glycans were essential for high-level IFN-alpha/beta induction by the mammalian-cell-derived virus. These results suggest that the failure of the mosquito cell-derived virus to induce IFN-alpha/beta is due to a lack of complex carbohydrates on the virion rather than the active suppression of the DC antiviral response.