Two Reviews on Immune Dysfunction

The current issue of Viral Immunology features two reviews that address different aspects of immune dysfunction. The first investigates the possible role of Staphylococcal enterotoxin B (SEB) in the pathogenesis of autoimmune diseases. SEB is a “superantigen” that is characterized by its ability to hyperactivate the immune system by directly crosslinking T cells with antigen-presenting cells. Superantigen-mediated activation of the immune system is largely independent of the T-cell specificity, and consequently, superantigens have been linked with the induction and relapse of various autoimmune diseases. In this context, Li et al. discuss the potential effects of SEB in the pathogenesis of autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). The authors point out that SEB stimulates the activation, expansion, anergy, and deletion of T cells and can trigger the excessive release of inflammatory cytokines. However, they also note that other studies have indicated SEB plays a protective role in the disease process, perhaps by acting as bidirectional regulating factors. The review also explores therapeutic approaches to neutralize SEB.

The second review analyzes the activation and exhaustion of adaptive immune cells in the context of hepatitis B virus (HBV) infection. It has been well established that immune system dysfunction is a hallmark of patients with chronic HBV infection, which leads to inadequate immune responses against the virus infection and its sequelae. Gogoi et al. point out that one of the major factors that contribute to inefficient immune function is immune exhaustion. Therefore, this review highlights the state of the field of immune effector functions and immune exhaustion in response to HBV infection.

Host defense mechanisms against viral infection are directed at the prevention of viral replication. Consequently, there is selective pressure on viruses to both circumvent host responses and boost replication efficiency, as illustrated by a study of Jiang et al. on viral factors affecting foot-and-mouth disease virus infection. However, human intervention through the administration of drugs can also play a key role in viral control. For example, Raheel et al. have developed an siRNA drug to target Dengue virus (DENV) replication. Cells transfected with DENV2SsiRNA2, which targets the structural region M of mature DENV2, were able to reduce DENV2 titer up to 85% in focus reduction assays. The data demonstrate that M represents a potential target for RNAi-based inhibitory approaches. An alternative approach to direct control of viral replication is to reduce the negative impacts of viral infection allowing more time for innate and adaptive immune responses to mediate viral control. This approach is illustrated by Awogbindin et al. who show that Kolaviron, a natural antioxidant and anti-inflammatory agent from Garcinia kola seeds, may be effective at delaying the development of clinical symptoms of influenza virus. Importantly, the drug preserved function of the lungs and reduced mortality in a mouse model of influenza virus infection.

The antibody response is also a major mechanism for controlling many viral infections. Therefore, mapping the location of viral protein epitopes and defining their degrees of conservation are important for understanding viral antigenic structure and virus–antibody interactions and for the subsequent development of diagnostics and vaccines. In this regard, Lagatie et al. have studied the antibody response to a 15mer peptide of the minor capsid protein, VP2, from JC polyomavirus. They concluded that rabbit immune serum can be used for immunohistochemical staining or western blot analysis of JC VP2 protein and used as a diagnostic for latent JC virus infection in humans. Also, in the area of diagnostics, Lin et al. note that recombinant single-chain variable antibody fragments (scFvs) have been proven to effectively inhibit many viruses, both in vitro and in vivo, and could be used as potential diagnostic and therapeutic reagents. The authors tested six chicken scFvs that were produced in prokaryotic expression systems and were specific for avian infectious bronchitis virus (IBV). They conclude that these antibody fragments may provide a new class of potent and selective anti-IBV reagents for diagnosing IBV infection, a cause of severe economic losses to the poultry industry.

Chen et al. have also been examining antibody epitopes for diagnostic and vaccine purposes, in this case with the equine arteritis virus, which mediates a respiratory and reproductive disease in horses. The authors identified a minimal linear peptide epitope within the viral nucleoprotein that shows promise as a diagnostic epitope. Finally, Erre et al. have analyzed antibody responses from a different angle. They point out that Epstein–Barr virus (EBV) infection has been implicated in the etiology of autoimmune diseases, including RA, but that data about EBV burden in RA patients from the Sardinian population, a genetic isolate with high prevalence of autoimmune diseases, have not yet been reported. They studied 135 Sardinian subjects (77 RA patients and 58 demographically matched healthy donors) in a cross-sectional case–control study and now report an association between EBV infection and RA in the Sardinian population. They further suggest that the potential influence of IL-6 inhibition on EBV load in RA patients should be further explored in prospective trials.

I would like to thank all of the authors for their excellent contributions to the journal and all of the reviewers for their time, energy, and expertise in providing critical reviews of all of the submissions the journal receives.