CRISPR-Cas Technology in Viral Therapeutics

The current issue of Viral Immunology features two interesting reviews that address therapeutic approaches to viral infection. Wahid et al. review clustered regularly interspaced palindromic repeats (CRISPR)/Cas systems. These systems have evolved as prokaryotic defense mechanisms that inactivate viruses by targeting and destroying their DNA genome. Importantly, researchers can now take advantage of these systems and manipulate them to target essentially any DNA sequence. The authors discuss how the technology can be used to combat viral infections in clinical settings through its reproducibility, high potency, ease of use, and limited off-target activity. In a second review, Zayed and colleagues point out that hepatitis C virus (HCV) is a major cause of chronic liver disease and cirrhosis that leads to liver failure and hepatocellular carcinoma, requiring liver transplantation. The authors review the epidemiology, natural history, and treatment options for patients with HCV-4 infection. HCV is also the subject of a commentary by Afzal and Iqbal in this issue.

Several articles focus on the role of host innate immunity in controlling viral infections. Wang et al. note that dysfunctional super oxide dismutase 2 (SOD2) is associated with a number of various human diseases including cancer, neuron diseases, and myocardial defects. However, the connections between SOD2-mediated oxidative homeostasis and the innate immune response remain unclear. The authors now show that SOD2 is a crucial regulator of antiviral signaling, suggesting a key role in regulating antiviral innate immunity. Sánchez-Leyva et al. have investigated the association of tumor necrosis factor (TNF)-α gene polymorphisms with the clinical manifestations of dengue virus infection. Their data suggest a minimal effect of the targeted TNF-α gene polymorphisms in dengue patients. Kullaya et al. have studied the role of platelets in host defense against respiratory syncytial virus (RSV). Their data suggest that platelets may play a role in the clearance of RSV viremia by internalizing viral particles and by enhancing type I interferon production from peripheral blood mononuclear cells (PBMCs), which subsequently exert antiviral effects on host cells.

Two additional articles in this issue of Viral Immunology focus on vaccination strategies. Zhou and colleagues have developed a DNA vaccine against herpes simplex virus type 2 (HSV-2). Vaccination in mice revealed strong adaptive (humoral and cellular) immune responses to HSV-2 along with enhanced protective immune responses against HSV-2 challenge. In a second article, Lind et al. note that increased narcolepsy incidence was observed in Sweden after the 2009 influenza vaccination with Pandemrix^®. They report an altered immune response among childhood narcolepsy patients toward influenza nucleoproteins and demonstrate increased antibody levels but lower nucleoprotein antibody affinity in narcolepsy patients. The final immunological mechanisms connecting Pandemrix to narcolepsy remain elusive but this study suggests that future investigation should be focused on the protein components of the vaccine.

Finally, two articles address epidemiological questions. Rossi and colleagues investigate the association between BK polyomavirus types 1 and 4 capsid antibody and natalizumab-associated progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis. Their data suggest that a robust immune response to BK polyomavirus may be protective against the development of PML. Mehmood and colleagues observe the presence of HCV RNA or NS5A in isolated PBMCs in patients that test negative for these elements in plasma. These data suggest that PBMCs may act as a reservoir for HCV and that the detection of HCV RNA and NS5A protein in PBMCs may be an additional diagnostic tool for hepatitis C patients.

I would like to thank both the authors for their excellent contributions to the Journal and all of the peer reviewers who work to ensure the high quality of the published articles.