Abstract
Several papers focus on the early innate immune response to viral infections. Dimitry Chistiakov opens the issue with a review of the relationship between an interferon-induced, viral RNA-sensing, helicase- and enterovirus- or picornovirus-induced autoimmunity. Interestingly, there appears to be an association between the level of helicase expression and type 1 diabetes in susceptible individuals. One of the earliest events in an immune response to infection is the activation of dendritic cells and the subsequent orchestration of the immune response by these cells. The role of plasmacytoid dendritic cells in the control of foot-and-mouth disease virus (FMDV) has been investigated by Golde and colleagues. FMDV, a virus that causes a highly contagious disease of livestock, is very sensitive to type I interferons (IFNs). However, the virus is able to suppress IFN production by skin and myeloid dendritic cells. The authors now extend these observations to show that there is also suppression of IFN production by plasmacytoid dendritic cells, resulting in an abrogation of the innate immune response. Another factor in the control of the innate response to infection is the production of prostaglandins. Cyclooxygenase (COX-1 and COX-2)-derived prostaglandins are involved in a variety of physiological processes, including the regulation of vascular tone and lung function, tissue remodeling, and the regulation of alveolar macrophages. Ackermann and colleagues have investigated the pulmonary cellular localization and distribution of COX-1 and COX-2 in a neonatal lamb model following respiratory syncytial virus (RSV) and parainfluenza virus 3 (PI3) infections. The authors show that RSV and PI3 infections differentially affect the cellular expression of COX-1 and COX-2. Interestingly, COX-2 expression is upregulated in airway bronchiolar and bronchial epithelial cells and macrophages, suggesting that it may be a potential target for RSV and PI3 therapy. Angel and colleagues have investigated the regulation of interleukin-12 (IL-12) expression in the context of human immunodeficiency virus (HIV) infection. The authors show that different signaling pathways are involved in the induction of IL-12p40 expression in primary monocytes versus a leukemic cell line, THP-1. Furthermore, HIV infection differentially affects these different signaling pathways. Recent experience with influenza indicates that cross-species infections and cross-subtype mutations are not as difficult as previously thought. Yan and Wu have analyzed the matrix protein 1 family of influenza A virus. Their data show that the inter-species/subtype variations are generally much smaller than the intra-species/subtype ones, supporting the idea that the barriers between species and between subtypes are not strong for influenza A viruses.
T cells are a major component of the adaptive immune response to viral infections. The effective regulation of these responses is critical for control of viral infections, yet the underlying regulatory mechanisms are poorly understood. Asthana and colleagues investigated the lymphoproliferative responses and T-cell subsets in HIV-1-infected patients showing strong or poor restoration of CD4 T cells following highly-active antiretroviral therapy (HAART). Their data show that CD8 T-cell function in these patients corresponds to CD4 T-cell numbers, suggesting that CD4 T cells are required for maintenance of protective CD8 T-cell responses to HIV-1. T-cell responses are also controlled by regulatory T cells (Tregs). The role of Tregs in the control of immunity to hepatitis B virus (HBV) was investigated by Bai and colleagues. The authors show that increased frequencies of CD4+CD25high Tregs and the expression of regulatory molecules on CD4+ T lymphocytes may inhibit the cellular immune response against HBV and affect viral clearance, leading to the persistence of chronic HBV infection. The utilization of HAART in long-term HIV-infected hemophilia patients can result in the loss of autoantibodies against CD4+ PBLs, suggesting that the treatment can block autoimmunity development or maintenance. Daniel and colleagues demonstrate increased numbers of CD4+ T cells with a suppressive phenotype, and downregulated IL-7R expression on CD8+ T cells in the blood of long-term HIV-infected hemophilia patients. The authors suggest that these factors could explain the decrease in autoimmunity.
The development of an immune response to a viral infection inevitably results in the development of some level of immunopathogenesis. Several papers address this issue in the context of different viral infections. Gou and colleagues have investigated the serum levels of connective tissue growth factor (CTGF) in patients with virus hepatitis B. They show a strong correlation between CTGF concentration and the stage of hepatic fibrosis. The role of tumor necrosis factor-α (TNF-α) in coxsackievirus B3 (CVB3)-induced cardiac inflammation (myocarditis) has been investigated by Sally Huber. Interestingly, myocarditis occurs in male but not female C57BL/6 mice, and the protection seen in females correlates with reduced expression of TNF-α and IL-1β in the heart. Treatment of females with recombinant TNF-α restores myocarditis susceptibility in wild-type, but not CD1d knockout mice. These data indicate an important role for CD1d expression in the control of disease susceptibility. Several studies have shown that enteroviral RNA can be detected in blood at the onset of type 1 diabetes, suggesting its role in the initiation of disease. To address this issue, Schulte and colleagues have analyzed the relationship between enterovirus infection and other genetic factors in the triggering of type 1 diabetes. The authors found that type 1 diabetes patients may have delayed enterovirus clearance, with virus detected predominantly in peripheral blood mononuclear cells. However, no obvious linkage was found with polymorphisms in two potential susceptibility genes, melanoma differentiation-associated gene 5 and 2′-5′ oligoadenylate synthetase 1. Finally, Poovorawan and colleagues have assessed the immune response to the newly resurging Chikungunya virus. They show that the levels of IL-18 and IL-18-binding protein were elevated in the serum of patients with Chikungunya infection. These data suggest that Chikungunya virus infection promotes T-helper 1 cell response by inducing IL-18 production, and that manipulation of IL-18 and IL-18-binding protein levels could be a promising new therapeutic approach.
The exciting science presented in this first issue of 2010 is a testament to the efforts of a great many individuals who have worked tirelessly in the background to enhance the quality of the journal. They include my colleagues at Mary Ann Liebert and the large number of reviewers who donate considerable time and energy to reviewing the papers submitted to the journal. I am especially grateful to the reviewers who have to endure numerous requests and telephone calls from me to ensure a smooth review process. A list of the reviewers who assisted with the journal in 2009 is included in this issue.