Immune responses against persistent viral infections: possible avenues for immunotherapeutic interventions.

Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Critical Reviews in Immunology (Impact Factor: 3.89). 02/2008; 28(2):159-83. DOI: 10.1615/CritRevImmunol.v28.i2.40
Source: PubMed

ABSTRACT Persistent viral infections present a significant threat to society, and treatment options for infected individuals are in urgent demand. During viral persistence, the balance between the virus and the host immune response is crucial. The immune system keeps the virus in check, and the virus counters by evading the immune response to avoid clearance, ultimately tipping the balance in favor of the virus and causing disease in many cases. Thus, efforts to tip the balance in favor of the host through immunotherapy holds promise for establishing control of viral replication. However, in most persistent viral infections, the continuous presence of the viral antigen renders virus-specific T cells to become dysfunctional. These differences can range from severe functional impairments in high-load persistent infections, to more subtle changes in infections with a lower virus burden. Recent work has shed light on immunoregulatory molecules or cytokines that affect viral persistence and/or T-cell function, and interventions that modulate these factors have led to effective viral control in experimental models. Exploitation of these experimental therapies may lead to treatments that would be of great clinical benefit to patients suffering from persistent virus infections, such as HIV, HBV, or HCV, or the herpesviruses CMV and EBV.

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    • "During evolution, metazoans have acquired a multitude of defense mechanisms that protect them against deleterious effects from pathogenic viruses. In spite of this, a number of viruses infecting diverse organisms are able to resist these defenses and establish persistent infections (Britt, 2008; Dasgupta et al., 1994; Fuse et al., 2008; Kuno, 2001; Oldstone, 2006). The molecular mechanisms underlying establishment of persistent infections remain incompletely understood, but they are likely based on an equilibrium between host defense responses and the counter-responses by the virus. "
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