Immunity to Viruses in Immunodeficient Hosts

Cytomegalovirus (CMV) is a double-stranded DNA virus that infects the majority of individuals in the United States. In most cases the infection is asymptomatic or produces only mild symptoms similar to a minor influenza virus infection. However, the virus is able to establish latency and persist for the life of the individual. Although the virus is latent, it continually reactivates, setting up a standoff between the virus and host. In most healthy individuals, the immune system maintains full control over the virus. But in individuals with weakened immune systems, such as bone marrow transplant patients, the virus reactivates and causes disease. Consequently, CMV is a significant cause of morbidity and mortality in immunocompromised hosts, many of whom undergo significant periods of lymphopenia. In the current issue of Viral Immunology, Shah and colleagues point out that the impact of subsequent immune reconstitution on T cell responses and pulmonary pathology in these individuals is poorly understood. To address this issue, the authors use a model of primary murine CMV (MCMV) infection in mice treated with cyclophosphamide to study the relationship of T cell reconstitution to pneumonitis pathology. Their data indicate that MCMV/cyclophosphamide pneumonitis is characterized by a massive infiltration of MCMV-specific T cells upon immune reconstitution. This immune response was associated with augmented proliferative capacity of functional viral-specific T cells and effective viral clearance. Interestingly, although the response was protective against lethal viral infection, it also resulted in demonstrable immunopathology. The authors conclude that, given the increasing use of cytoreductive therapies in hematopoietic transplant and other disorders, further studies are needed to determine the mechanisms that regulate this response.

Other articles in this issue of Viral Immunology address various aspects of the host response to viral infection with a view to enhancing the design of future vaccines. Krylova and colleagues point out that although immune mechanisms are known to be important in controlling tick-borne encephalitis virus (TBEV) infection, the interactions of different TBEV with the innate and adaptive immune system are poorly understood. To address this issue, the authors investigated the ability of two TBEV strains to modulate the expression of membrane molecules on human immune cells. They conclude that TBEV infection induced or suppressed various adhesion and activation receptors, potentially influencing the virus' virulence and pathogenicity. Immune responses to Hantaan virus infections are also poorly understood. In this regard, Wang et al. have investigated the kinetics and immunodominance of virus-specific T cell responses to Hantaan virus infection. They observed a limited T cell response in patients during the early stages of the infection and suggest that this may play a role in influencing the severity of the infection. Rahal et al. note the potential association between the Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6) infections and an increased risk of autoimmune disease development. They speculate that the constant shedding of viral antigens, including viral DNA, may contribute to autoimmune mechanisms, and address this idea in mice that were injected with either EBV or HHV-6A DNA. Interestingly, they found that viral DNA triggers the production of the proinflammatory cytokine IL-17, a cytokine that has been shown to play a role in autoimmune diseases. This is consistent with the authors' hypothesis.

Approaches to modulate immune responses to viral infections by vaccines or drugs are also addressed in this issue. In the case of vaccines, it is well established that adjuvants play a critical role in boosting immune responses elicited by target antigens. One such adjuvant is CpG DNA. In this regard, Li and colleagues have studied the adjuvanticity of CpG motif in porcine circovirus type 2 (PCV2) DNA vaccines in Changbai piglets. They report that CpG motifs boosted both the humoral and cellular immune responses generated by the vaccine. Noreen et al. have focused on developing drugs for the control of hepatitis C virus (HCV) infection, a worldwide health problem that affects about 300 million individuals. The authors show that a methanolic extract of Portulaca oleracea specifically blocked HCV NS3 protease expression in a dose-dependent fashion. Thus, this extract and its potential constituents potentially offer a new option for treating chronic HCV infection.

Finally, Rendón-Ramirez et al. have investigated serum levels of inflammatory cytokines in order to assess their usefulness as biomarkers of pandemic influenza A infection and their association with fatal cases. The study indicates that TGF-β levels are a useful tool for differentiating influenza A virus from other causes of pneumonia progressing to sepsis.

I would like to thank all of the authors for their outstanding contributions to Viral Immunology and the manuscript reviewers for their help in ensuring the high quality of articles selected for publication.