Restoring immune defenses via lymphotoxin signaling: lessons from cytomegalovirus.
Although primary infection with human cytomegalovirus (HCMV), a beta-herpesvirus, is widespread and acquired early in life, it rarely causes disease in immune-competent individuals. However, in immune-compromised patients HCMV infection or reactivation invariably leads to serious disease, the effective treatment of which remains a difficult clinical problem. Current antiviral therapy is limited not only by toxicity but also by the continual emergence of drugresistant viruses. The limitations of these current therapeutics provides a strong impetus to develop novel approaches that will enhance the host's immune responsiveness while at the same time effectively controlling virus replication. Type I interferon (IFN) plays a critical role in initiating innate antiviral defenses and promoting adaptive responses and lymphotoxin (LT)-alphabeta has recently been identified as an essential effector cytokine regulating the induction of type I IFN during CMV infection. In particular, CMV infection of immune-compromised mice has revealed the immunotherapeutic potential of the lymphotoxin-beta receptor (LTbetaR) signaling pathway to restore immune function and provide protection from CMV mortality. In this review, we discuss the potential benefits and risks associated with LTbetaR-directed immunotherapy for CMV disease and other persistent viral infections.
Banks
Theresa A
TA
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Rickert
Sandra
S
Ware
Carl F
CF
D000818:Animals; D002986:Clinical Trials as Topic; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology*; D051379:Mice; D011247:Pregnancy
D047908:Intracellular Signaling Peptides and Proteins; D008233:Lymphotoxin-alpha