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Journal of Virology, January 2007, p. 237-247, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01590-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Differential Induction of Type I Interferon Responses in Myeloid Dendritic Cells by Mosquito and Mammalian-Cell-Derived Alphaviruses{triangledown}

Reed S. Shabman,1,2,3 Thomas E. Morrison,1,2,3 Christopher Moore,4 Laura White,2,3 Mehul S. Suthar,1,2,3 Linda Hueston,5 Nestor Rulli,5 Brett Lidbury,5 Jenny P.-Y. Ting,4 Suresh Mahalingam,5 and Mark T. Heise1,2,3*

Department of Genetics,1 Department of Microbiology and Immunology,2 The Carolina Vaccine Institute,3 The Lineberger Comprehensive Cancer Center, University of North Carolina—Chapel Hill, Chapel Hill, North Carolina 27599,4 University of Canberra, Canberra, Australia5

Received 25 July 2006/ Accepted 10 October 2006

Dendritic cells (DCs) are an important early target cell for many mosquito-borne viruses, and in many cases mosquito-cell-derived arboviruses more efficiently infect DCs than viruses derived from mammalian cells. However, whether mosquito-cell-derived viruses differ from mammalian-cell-derived viruses in their ability to induce antiviral responses in the infected dendritic cell has not been evaluated. In this report, alphaviruses, which are mosquito-borne viruses that cause diseases ranging from encephalitis to arthritis, were used to determine whether viruses grown in mosquito cells differed from mammalian-cell-derived viruses in their ability to induce type I interferon (IFN) responses in infected primary dendritic cells. Consistent with previous results, mosquito-cell-derived Ross River virus (mos-RRV) and Venezuelan equine encephalitis virus (mos-VEE) exhibited enhanced infection of primary myeloid dendritic cells (mDCs) compared to mammalian-cell-derived virus preparations. However, unlike the mammalian-cell-derived viruses, which induced high levels of type I IFN in the infected mDC cultures, mos-RRV and mos-VEE were poor IFN inducers. Furthermore, the poor IFN induction by mos-RRV contributed to the enhanced infection of mDCs by mos-RRV. These results suggest that the viruses initially delivered by the mosquito vector differ from those generated in subsequent rounds of replication in the host, not just with respect to their ability to infect dendritic cells but also in their ability to induce or inhibit antiviral type I IFN responses. This difference may have an important impact on the mosquito-borne virus's ability to successfully make the transition from the arthropod vector to the vertebrate host.

* Corresponding author. Mailing address: The Carolina Vaccine Institute, The University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 843-1492. Fax: (919) 843-6924. E-mail: heisem{at}med.unc.edu.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 237-247, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01590-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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