Abstract
T
HBV causes chronic infections of the liver and is responsible for approximately one-third of all the cases of liver cirrhosis and more than three-quarters of hepatocellular carcinoma worldwide. Zhang and colleagues point out that there is a positive correlation between viral load, the level of viral splicing variants, and the high risk of hepatocellular carcinoma. In this regard, the authors have identified a new natural splice variant characterized by two stretches of deleted nucleotides. They go on to show that this variant significantly enhances HBV replication in vitro and suggest that it may have an important influence on HBV replication and viral persistence. In a separate study, He et al. have studied HBV infection in the context of vaccination. They show that immunity against HBV infection gradually decreased in children 15 and younger who received the HBV vaccine during infancy in China. They recommend that repeated vaccination or additional booster vaccinations for children at, or before, age three are necessary to induce more durable immunity to HBV. The mechanism by which HBV escapes immunity and establishes a persistent infection is incompletely understood. In this regard, Jiang et al. have investigated whether changes in peripheral blood mononuclear cells (PBMCs) occur in patients with HBV infection. They show that for patients in the immune tolerance phase, α-mannosidase I expression is linearly correlated with hepatitis B antigen titers and the level of HBV DNA. The authors suggest that increased expression of α-mannosidase I in PBMCs plays an important role in HBV immune escape and that the expression level is closely related to the viral replication activity.
Another virus that establishes a persistent infection is HIV-1. Gonzalez-Diaz et al. point out that the virus induces immune exhaustion characterized by a loss of effector functions of immune cells such as proliferation, production of cytokines, and cytotoxic potential. This has been attributed to an increased response of regulatory T cells (Tregs) and recently to the expression in different cell populations of inhibitory molecules, such as PD-1, CTLA-4, Tim-3, and LAG-3. The authors discuss the functional role of Treg cells and inhibitory molecules during the development of immune exhaustion as well as their therapeutic potential. Sealy and colleagues point out that although cocktail vaccines have been developed using antibody reactivity patterns against variant pathogens (e.g., polio virus and pneumococcus), a vaccine cocktail comprising diverse viral membrane antigens has not yet been advanced to a clinical efficacy study in the HIV-1 field. The authors go on to describe the preparation of mouse antibodies specific for HIV-1 gp140 or gp120 envelope molecules with precise discriminatory capacity against their respective immunogens. They argue that these antibody reagents will ultimately support high-throughput studies to develop successful HIV-1 envelope cocktail vaccines.
Two other articles in this issue of Viral Immunology address other aspects of the interactions between the virus and host. Farrag and Almajhdi review the role of innate immunity in the clearance and disease progression of human respiratory syncytial virus (HRSV). The authors focus on the role of pulmonary innate defenses in HRSV clearance and the extent to which they participate in disease progression. They additionally discuss immune responses associated with HRSV vaccines. Chinnaswamy and colleagues also discuss innate immunity in the context of the expression of the human IFNL4 gene. They specifically identify key roles for the virus-inducible transcription factors, NF-κB, IRF3, and IRF7, in driving IFNL4 gene expression. This is one of the first reports on the functional characterization of the human IFNL4 promoter.
I would like to thank all of the authors for their excellent submissions to Viral Immunology and all of the reviewers for their careful review of the submitted articles.