T he superfamily of human Class II cytokines contains interleukin-10 (IL-10), the IL-10 -related interleukins , the interferons (IFN-␣, -␤ -, -, -, and -␥) and the interferon-like molecules IL-28A, IL-28B, and IL-29 (also referred to as lambda interferons). 1 Collectively, these molecules modulate innate and adaptive immune responses to environmental pathogens and protect the host against diseases such as cancer. The best-characterized class II cytokines are the type I interferons, whose expression is tightly regulated by viral infection. 2 After binding, these proteins induce a large set of interferonstimulated genes (ISGs) that inhibit viral replication and activate numerous downstream cellular responses involving dendritic cells, lymphocytes, and macrophages. 3 In addition to the type I interferons, viral infection also stimulates the rapid production of IL-28 and IL-29, a related, but distinct subset of the class II cytokine superfamily. 4,5 These proteins also possess potent antiviral activity; however, in contrast to the type I interferons, they bind a heterodimeric receptor consisting of the IL-28R␣ 4,5 subunit and the IL-10R␤ subunit, a receptor subunit that is also shared by IL-10, Chronic viral hepatitis is the leading cause of liver disease and may play a role in the pathogenesis of lesions characteristic of cirrhosis, hepatocellular carcinoma, and end-stage liver failure. The two major causes of chronic viral hepatitis are hepatitis B virus (HBV), a DNA-containing member of the Hepadnaviridae family that infects approximately 350 million people worldwide, 7 and hepatitis C virus (HCV), an RNA virus of the Flaviviridae family that infects approximately 170 million individuals worldwide. 8 IFN-␣ is an approved treatment for both types of chronic viral hepatitis and has demonstrated considerable clinical success. [9][10][11] However, this cytokine is ineffective for a substantial percentage of infected individ-

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Very little is known about the developmental stages of Aspergillus fumigatus during invasive aspergillosis. We performed real-time reverse transcription-PCR analysis on lung samples from mice with invasive pulmonary aspergillosis to determine the expression of A. fumigatus genes that are expressed at specific stages of development. In established infection, A. fumigatus exhibited mRNA expression of genes specific to developmentally competent hyphae, such as stuA. In contrast, mRNA of genes expressed by conidia and precompetent hyphae was not detected. Many genes required for mycotoxin synthesis, including aspHS, gliP, mitF, and metAP, are known to be expressed by developmentally competent hyphae in vitro. Interestingly, each of these genes was expressed at significantly higher levels during invasive infection than in vitro. The expression of gliP mRNA in vitro was found to be highly dependent on culture conditions. Furthermore, gliP expression was found to be dependent on the transcription factor StuA both in vitro and in vivo. Therefore, developmentally competent hyphae predominate during established invasive infection, and many mycotoxin genes are expressed at high levels in vivo. These results highlight the importance of the evaluation of putative virulence factors expressed by competent hyphae and analysis of gene expression levels during invasive infection rather than in vitro alone.