Viral Inhibition of Antigen Presentation

Specific identification of viral antigens (as opposed to self-antigens) is critical for the adaptive immune system to respond to and eliminate virally infected cells. In the case of T cells, virally infected cells are recognized by their display of viral peptide/major histocompatibility molecule complexes on the cell's surface. In short, virally infected cells display their status on the cell's surface to allow rapid T-cell recognition and response. As a countermeasure, many viruses have evolved mechanisms to interfere with the antigen presentation process. This can confer a significant advantage to the virus by protecting the infected cell from destruction and allowing more time for viral replication. In the current issue of Viral Immunology, two articles specifically address two mechanisms by which viruses interfere with the cell's antigen processing machinery. Cardoso et al. have investigated the infection of monocyte-derived bovine dendritic cells by different strains of bovine viral diarrhea virus (BVDV). Infection of nonadherent peripheral monocytes with BVDV inhibited the ability of the cells to present a third-party antigen to primed CD4⁺ T cells within the first 24 h of infection. This effect was dependent on live virus infection. Taken together, the data indicate that active infection is interfering with dendritic cell maturation and highlight an important role of infected dendritic cells in BVDV-induced immunopathogenesis.

In a second article on this topic, Liu et al. investigate one of the many immune evasion tactics employed by herpes simplex virus (HSV). The authors point out that one key evasion mechanism of HSV is to downregulate CD1d-mediated activation of natural killer T cells. Previous studies have indicated that modification of the cytoskeleton can alter CD1d-mediated antigen presentation. Here they show that an HSV-1 virus lacking a viral protein, VP22, was impaired in its ability to inhibit CD1d-mediated antigen presentation (as compared with the wild-type virus). These, and additional, data led the authors to conclude that VP22 is required (but not sufficient) for the inhibition of CD1d-mediated antigen presentation by an HSV-1 infection. Together these contributions highlight the critical role that immune evasion mechanisms play in the interplay between viruses and their hosts.

Two articles in this issue address gene polymorphisms and disease outcomes. Martins-Feitosa and colleagues have analyzed gene polymorphisms and serum levels of pro- and anti-inflammatory markers in dengue virus infections. Their data highlight the complex relationship between cytokine expression and various gene polymorphisms. In contrast, Schulte et al. have focused on the relationship between the strength of innate antienteroviral responses to a specific polymorphism in the MDA5 gene (an innate immune sensor). They specifically investigate the linkage in children at risk for type 1 diabetes. Interestingly, their data indicate a difference in the responses to enterovirus and enterovirus–antibody complexes in diabetes patients carrying the risk genotype compared with heterozygotes, which may influence control of enterovirus clearance.

The development of new vaccines is always a hot topic for the Journal. In the current issue, Ashfaq and Ahmed have addressed the very urgent issue of Zika virus vaccine development. Zika virus is a positive single-stranded RNA virus that is transmitted by mosquitoes and for which no vaccines and antiviral drugs are available. Therefore, the authors have identified several putative B-cell and T-cell epitopes that are conserved among Zika virus genomes. These predicted epitopes may be important for the future design of vaccines against this clinically important virus. Kang et al. have turned their attention to infectious hematopoietic necrosis virus (IHNV), which infects salmonid fish. The virus has serious economic consequences for aquaculture and there is no commercially available vaccine. In this regard, the authors have developed an inactivated virus vaccine that confers significant protection in rainbow trout challenged with live IHNV. These results provide an important foundation for further development of inactivated IHNV vaccines.

Finally, three additional articles in this issue address various aspects of viral immunology. Fikatas and colleagues have investigated the serological status of the central and western Greek population against six nonpolio enterovirus strains and the Sabin 1, 2, and 3 vaccine strains. Based on their findings, they speculate that changes in the antigenic properties of circulating viruses are due to the selection of variants that are less prone to be neutralized by human antibodies. Clearly, further studies are warranted to determine whether this will lead to future epidemics driven by the appearance of highly evolved viral variants. Manzoor et al. note that purinergic P2X receptors are gated ion channels that respond to varying ATP concentrations in the extracellular environment. Here they quantify the expression of P2X7 and P2X4, along with selected host genes, in the blood of patients who are chronically infected with hepatitis C virus (HCV). Their data highlight the roles of P2X4 and P2X7 receptors in mediating antiviral immunity against HCV and in inducing HCV pathogenesis. The final article in this group focuses on the association between vitamin D deficiency and susceptibility to a number of different types of viral infections. Maghzi and colleagues have studied the role of vitamin D in acute infectious mononucleosis (IM). Their data show significantly lower vitamin D levels in IM patients at the time of infection than in a control group, suggesting that deficiency in the vitamin may be an important risk factor for the development of IM.

I would like to thank all of the authors for their contributions to the Journal and all of the reviewers for their efforts to ensure the excellence of the published manuscripts.