title: Adaptive and innate transforming growth factor beta signaling impact herpes simplex virus 1 latency and reactivation.
abstract: Innate and adaptive immunity play important protective roles by combating herpes simplex virus 1 (HSV-1) infection. Transforming growth factor β (TGF-β) is a key negative cytokine regulator of both innate and adaptive immune responses. Yet, it is unknown whether TGF-β signaling in either immune compartment impacts HSV-1 replication and latency. We undertook genetic approaches to address these issues by infecting two different dominant negative TGF-β receptor type II transgenic mouse lines. These mice have specific TGF-β signaling blockades in either T cells or innate cells. Mice were ocularly infected with HSV-1 to evaluate the effects of restricted innate or adaptive TGF-β signaling during acute and latent infections. Limiting innate cell but not T cell TGF-β signaling reduced virus replication in the eyes of infected mice. On the other hand, blocking TGF-β signaling in either innate cells or T cells resulted in decreased latency in the trigeminal ganglia of infected mice. Furthermore, inhibiting TGF-β signaling in T cells reduced cell lysis and leukocyte infiltration in corneas and trigeminal ganglia during primary HSV-1 infection of mice. These findings strongly suggest that TGF-β signaling, which generally functions to dampen immune responses, results in increased HSV-1 latency.
authors: Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery and Regenerative Medicine Institute, Los Angeles, California 90048, USA.
authors: Sariah J
authors: SJ
authors: Allen
authors: Kevin R
authors: KR
authors: Mott
authors: Steven L
authors: SL
authors: Wechsler
authors: Richard A
authors: RA
authors: Flavell
authors: Terrence
authors: T
authors: Town
authors: Homayon
authors: H
authors: Ghiasi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005123:Eye / Q000821:virology; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000276:immunology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D012376:Rodent Diseases / Q000276:immunology / Q000821:virology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000276:immunology / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D016212:Transforming Growth Factor beta