Purchase this article with an account.
L. Benmohamed, X. Zhu, T.V. Ramos, S.L. Wechsler, A.B. Nesburn; Impairment of Adaptive Immunity by Herpes Simplex Virus Type 1 Latency–Associated Transcript . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1654.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: In adaptation to the immune system, the members of the Herpesviridae family have developed manifold mechanisms by which expression of viral genes inhibits recognition by T cells. This may be important in herpes life–long latent infection. HSV–1 can infect dendritic cells (DCs), the most important antigen presenting cell type in the immune system, and interfere with their function of Ag presentation to T cell. Yet, the stimuli and the viral genes involved in such interference remain unknown. In this study, the potential role of the Latency Associated Transcript (LAT) in this interference the only viral gene abundantly transcribed during both acute and latent infection, is investigated. Methods: Mice were infected either with i) the LAT null mutant dLAT2903; ii) its marked rescued virus dLAT2903R or iii) the wild–type HSV–1 strain McKrae. Herpes specific local and systemic B and T cell responses were investigated during both acute and latent infections. Bone marrow derived DCs were infected in vitro with dLAT2903, dLAT2903R or McKrae and their phenotypic and functional maturation studied. Results: LAT inhibited maturation of DCs and impaired the host T–cell function. In vivo infection with LAT(+) virus compared to LAT(–) virus resulted in fewer T–cells at the site of HSV–1 latency (trigeminal ganglia) and in an impairment of herpes specific Th1 responses. Dendritic cells exposed in vitro to LAT(+), but not to LAT(–) virus, and then stimulated with lipopolysaccharide did not up–regulate MHC, co–stimulatory or adhesion molecules, secreted greatly diminished amounts of pro–inflammatory cytokines, and displayed diminished T cell stimulatory capacity. Conclusions: These results revealed a novel immuno–evasion mechanism whereby HSV–1 LAT directly or indirectly impaired host cellular immunity.
This PDF is available to Subscribers Only