Type I interferons (IFNs) (alpha/beta interferon [IFN-␣/␤]) are expressed as a first line of defense against viruses and are known to play a critical role in the antiviral response (38). Type I IFNs combat viruses both directly by inhibiting virus replication in the cells and indirectly by stimulating the innate and adaptive immune responses (38). The direct antiviral activity of type I IFNs is exerted by a number of different mechanisms, e.g., blockage of viral entry into the cell, control of viral transcription, cleavage of RNA, and preventing translation (16,31,37). In addition to the direct effects, type I IFNs play immunoregulatory roles and thereby shape the innate and adaptive immune responses. For instance, IFN-␣/␤ induce natural killer cell cytotoxicity and up-regulate expression of major histocompatibility complex class I on most cells and costimulatory molecules on antigen-presenting cells (9, 37). Furthermore, type I IFNs enhance cross-presentation of exogenous antigen in major histocompatibility complex class I and promote T-cell expansion (14,19,36 (11,15,20,23,32), although they exert their action through a receptor complex distinct from the type I IFNs (20,32). Most of the reports demonstrating antiviral activity of IFN-have addressed the issue in an in vitro experimental setup, but one report has shown that a recombinant IFN--expressing vaccinia virus is attenuated in vivo (4), whereas recombinant IFN-had no antiviral effect in vivo in the transgenic hepatitis B virus mouse model (30). Thus, we still do not have a clear picture of the antiviral potential of IFN-in vivo or of the mechanisms of action.The IFN-s have been demonstrated to be induced after stimulation with several single-stranded RNA (ssRNA) viruses, whereas the information on viruses with other genomes (DNA and double-stranded RNA [dsRNA]) is sparse (11). Virtually all cell types are capable of producing type I IFNs in response to viral infections, with the amount of IFN being virus and cell type dependent (7) and with plasmacytoid dendritic cells (pDCs) being the most potent producers of type I IFNs (3). IFN-s can be produced by a number of cell types, although the pattern of expression has not been elucidated. One report has demonstrated that IFN-s are produced by pDCs to a greater extent than by monocyte-derived DCs after influenza A virus (IAV) infection, suggesting that pDCs are the primary IFN--producing cells (13). However, this needs to be confirmed for other virus infections.Here, we have investigated the expression of type I and III IFNs after infection with DNA and RNA viruses in lymphoid, myeloid, and epithelial cell lines, and we have also examined the ability of type I and III IFNs to cross-induce one another. Subsequently, we investigated the antiviral activity of IFN-in

The first line of defense against viral infections is mediated by interferons (IFN)s, which are produced rapidly by the infected host. Type I IFNs (IFN-alpha/beta) are known to combat viruses both directly by inhibiting viral replication in the cells and indirectly by stimulating the innate and adaptive immune responses. Recently, a novel class of cytokines was discovered and named IFN-lambda (alternatively type III IFN or interleukin-28/29 [IL- 28/29]), based on IFN-like antiviral activity and induction of typical IFN-inducible genes. Here, we review the literature on IFN-lambda and discuss the current knowledge of the functions and mechanisms of action of IFN-lambda.

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