Vitamin A Influence on B Cell Class Switch Recombination

Vitamin A is an essential nutrient that is important for development and vision. It also plays an important role in the regulation of the immune system; deficiencies in vitamin A can significantly impair immune protection against viral infections. In this regard, vitamin A is reported to modify cytokine patterns, and may indirectly influence antibody isotype expression. In particular, it has been reported that the production of IgA, a first line of defense against viruses at mucosal sites, is inhibited when vitamin A is deficient. However, the underlying mechanisms of vitamin A regulation of immunity are still poorly understood. In the current issue of Viral Immunology, Hurwitz et al. hypothesize that vitamin A may also have a direct influence on the B cell heavy-chain class switch recombination event and have discovered hundreds of potential nuclear receptor response elements switch sites within immunoglobulin heavy chain loci. Their data suggest that nuclear receptors have a direct effect on the immunoglobulin heavy chain class switch recombination event. The authors' current thinking is that vitamin A receptors alter site accessibility to activation-induced deaminase and nonhomologous end joining machinery, thereby influencing the isotype switch to antibody IgA production. These fascinating data provide critical insights into the mechanism by which vitamin A regulates protection against viral infections at mucosal sites.

The current issue of Viral Immunology also features two reviews that address aspects of the immune response to two different viruses. Kariminik et al. review the innate immune response to BK virus, a member of the polyomavirus family. This virus, which is named after the initials of a renal transplant patient, can be a major factor in graft rejection, especially in kidney transplant patients. The current review discusses the roles played by innate immunity against BK virus and also the status of innate immunity in the patients with reactivating BK virus. In a second review, Gutierrez-Xicotencatl et al. discuss the humoral immune response against human papillomavirus (HPV), which is directly linked to the development of cervical cancer. The authors note that cervical cancer is one of the main causes of death among women of reproductive age and stress the need for better diagnostics for HPV. The authors review the antibody response against the HPV proteins during the development of the disease, as well as their possible use as biomarkers for the progression of cervical lesions and of cervical cancer.

Other articles in this issue address different aspects of the immune response to viral infection. Estrada-Jimenez et al. have investigated whether suppressors of cytokine signaling (SOCS) molecules are associated with dengue virus (DENV) evasion of the antiviral response. The authors' data suggest that this may be the case since overexpression of SOCS1 and SOCS3 induced by DENV infection leads to impairment of antiviral response through the inhibition of STAT1 and STAT2. Lei et al. have investigated the immune response to hepatitis E virus (HEV). HEV is one of the primary causative agents of acute hepatitis, but the underlying mechanisms of disease are poorly understood. The authors show that the HEV ORF3 protein attenuated lipopolysaccharide-induced cytokine production and chemotactic factors by inhibiting the nuclear factor-κB (NF-κB) signaling pathway. They speculate that this anti-inflammatory property might be important in chronic HEV infection and cirrhosis. Henriquez et al. have tested whether procalcitonin, a biomarker of inflammation, can be used to help make clinical decisions in patients with acute respiratory infections. Their data suggest that procalcitonin levels are not a useful test in acute respiratory infection of mild-to-moderate severity. Finally, Wen et al. have investigated the role of B and CD8 T cells in the immune response to human rotavirus. Using a gnotobiotic pig model, the authors show that the absence of B cells and CD8 T cells results in reduced viral control and increased virus shedding. The study demonstrates that gnotobiotic pigs are a valuable model for dissecting protective immune responses against viral infections.

I would like to thank all of the authors for their fine contributions to the Journal and all of the reviewers for their help in reviewing article submissions.