Viral Influences on Otherwise Noncommunicable Diseases

Two reports in the current issue of Viral Immunology address the involvement of viruses in otherwise noncommunicable diseases. It has long been known that viruses can induce secondary diseases, the most obvious example being the induction of certain cancers by viruses. However, for some diseases there is evidence for a viral role, but a formal association has not been demonstrated. For example, data suggesting that enteroviruses were associated with diabetes were published several decades ago. However, although subsequent meta-analyses of multiple studies demonstrated a significant excess of enterovirus infection associated with autoimmunity and type 1 diabetes compared with controls, it only partially explained the proportion of type 1 diabetes cases. Here, Niklasson et al. treat type 1 diabetes-like disease in a rodent model with picornavirus-specific antivirals and provide evidence that ongoing pathogenesis is due to one or more members of the Picornaviridae family. The authors note that their study serves as an example for studying viral etiology of the disease in humans. Therapy in humans could be initiated when diabetes is first diagnosed and possibly early enough for pancreatic beta cell rescue. In a similar report, Kumata and colleagues address the role of Epstein–Barr virus (EBV) in the development of Graves' disease. Graves' disease is an autoimmune thyroid disorder that mainly presents as hyperthyroidism and is caused by thyrotropin receptor antibodies (TRAbs) that stimulate thyroid-stimulating hormone receptors. The authors show that enhanced production of TRAb-IgM was frequently observed in patients with EBV reactivation. These results are consistent with the fact that the percentage of autoreactive IgM B cells is higher than that of autoreactive IgG B cells, and support the idea that this is due to EBV-related polyclonal B cell activation. Both articles add to our understanding of the possible role that viruses play in influencing noncommunicable diseases in both animals and humans.

Two articles in the current issue of Viral Immunology focus on influenza. Liepkalns and colleagues note that impairment of immune defenses can contribute to the severity of influenza virus infections. Since rapamycin is an immunosuppressive drug used to prevent transplant rejection and is currently undergoing clinical trials for treating cancers and autoimmune diseases, the authors investigated its impact on influenza virus infection in a mouse model. Their data indicate that rapamycin treatment did not adversely affect morbidity, mortality, or antibody production during lethal influenza virus challenge.

Vaccines are currently available against influenza although the efficacy of these vaccines is limited and tends to be strain specific. Along these lines, Ingle et al. remind us that broadly cross-reactive vaccines are urgently needed against influenza viruses, especially given that highly pathogenic H5N1 viruses with high mortality in humans continue to circulate and evolve. Here, the authors evaluated hemagglutinin, highly conserved nucleoprotein, and ectodomain of matrix protein, either singly or in combination, as vaccines antigens in BALB/c mice. Different adjuvants were also tested. The data indicate that several adjuvant–immunogen combinations confer full protection in mice. The authors suggest that these combinations require further evaluation in higher animals.

Finally, two articles investigate different aspects of chronic virus infections. Kallas et al. note that intravenous drug use is one of the most important transmission routes for blood-borne viruses, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Although it is known that these infections alter the subset distributions of T cells, there is only limited information on the impact of HIV, HBV, and/or HCV coinfections. To address this issue, the authors compared blood samples from Caucasians who inject drugs and age-matched subjects negative for all three infections. Their data indicate that an altered T cell subset distribution among drug users is mainly triggered by HIV infection and/or intravenous drug use, whereas HBV and/or HCV seropositivity has minimal additional effects on T cell distribution. Finally, Pulido and colleagues note that toxicities related to the use of nucleoside analogues have stimulated interest in developing nucleoside-sparing regimens against HIV. However, data regarding the use of CCR5 antagonists in this setting and in the naive scenario are scarce. Here, the authors investigate the immune–virological efficacy and tolerability of a low-dose, once-daily, maraviroc (MVC)-containing, nucleoside reverse transcriptase inhibitor-sparing dual therapy compared with that of standard triple therapy in the clinical practice setting. They show that a nucleoside-sparing MVC-containing dual therapy showed similar immune–virological efficacy and tolerability as standard triple therapy in naive HIV-infected patients. These findings may have important implications for future treatment regimens.

I would like to thank all of the authors for their excellent contributions to the Journal and all of the reviewers for their efforts in maintaining the high quality of articles published.