Abstract
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Recent studies have demonstrated that both Notch signaling and Th22 cells are involved in the pathogenesis of chronic hepatitis C virus (HCV) infection. However, the underlying mechanisms are not understood. Jiang and colleagues have examined the role of Notch signaling in regulating Th22 cell responses in HCV-infected patients. The frequency of Th22 cells was elevated in chronically infected patients (compared with uninfected controls) and inhibition of Notch signaling downregulated HCV-specific Th22 cells and IL-22 production. The authors conclude that Notch signaling is a critical pathway that regulates the IL-22 response in chronic HCV infection and should be considered a therapeutic target. Merani and colleagues have also addressed the host response to HCV. They note that understanding this host–viral interplay has been difficult, given the asymptomatic nature of many acute HCV infections. They have approached this problem by studying a recent transmission case to determine whether adapted viral strains can be transmitted and influence the recipient's anti-HCV T cell response. Interestingly, HCV-specific T cell responses in the recipient were directed against peptides that matched low frequency viral variants in the donor. These data illustrate viral variation in the source strain and suggest that transmission of adapted viral species can direct the recipient's HCV-specific immune response during acute infection. Other viruses that mediate persistent infection include hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Omatola et al. point out that an increasing incidence of liver disease caused by HBV is linked to high morbidity and mortality among HIV-infected individuals. To determine the prevalence of HBV–HIV coinfection in Nigeria, the authors screened HIV-positive patients for HBV antigens. The high rates of coinfection observed in the study support the introduction of HBV vaccination as part of the national immunization program in Nigeria.
Cytomegaloviruses (CMVs) also establish persistent infections and are particularly prevalent, infecting >50% of the U.S. population. In immunocompromised patients, CMV infection can be associated with severe disease and intravenous immunoglobulin can be used to treat these cases. Aiba and colleagues have analyzed the interaction of intravenous immunoglobulin with CMV-infected cells and show that retardation of the infection depended on the CMV neutralizing antibody titer.
Two articles in this issue of Viral Immunology focus on the innate immune response to viral infection. Li and Karlsson have investigated the antiviral effect of 2,3-dioxygenase (IDO) on influenza virus infection. The authors show that infection mouse fibroblast cells with influenza virus elevated the number of transcripts for IDO. Experimental inhibition of IDO transcripts increased the levels of viral RNA, suggesting that IDO is involved in limiting the replication of influenza A viruses. He et al. point out that another key molecule of the innate immune system, toll-like receptor 3 (TLR3), recognizes double stranded RNA. To determine the impact of TLR3 on infectious bursal disease virus (IBDV), the authors analyzed the level of chTLR3 expression, and its downstream effectors, IFN-β and IL-8, were analyzed after IBDV infection of chicken peripheral blood mononuclear cells. Their data show that there is a correlation between the expression of TLR3, IFN-β, and IL-8 and the virulence of the IBDV strain tested. The authors conclude that TLR3 is involved in the pathogenesis of IBDV in commercial chickens, and its downstream effectors (IFN-β and IL-8) might play an important role in this process.
Finally, three articles focus on different aspects of vaccine development. Wang et al. have developed a multiepitope fusion antigen from Toxoplasma gondii that is expressed in a human HBV core antigen delivery vector. This prototype vaccine elicited strong humoral and cellular immune responses in a mouse model. Clifford et al. show that Th2 genes differentially impact the response to measles vaccine in individuals from different ethnic backgrounds from Mozambique. Another article reports a meta-analysis of CD4+ T cell epitope dominance in arbo-flavivirus envelope proteins. Data presented by Landry et al. suggest that differential processing may be partially responsible for variations in disease severity among arbo-flaviruses and point to structural features that modulate protection from disease.
I would like to thank the authors for their excellent contributions to the Journal and all of the reviewers who worked to ensure the quality of the published articles.