This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Leib, D. A.
Right arrow Articles by Ferguson, T. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leib, D. A.
Right arrow Articles by Ferguson, T. A.

 Previous Article  |  Next Article 

Journal of Virology, December 2009, p. 12164-12171, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01676-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Interaction of ICP34.5 with Beclin 1 Modulates Herpes Simplex Virus Type 1 Pathogenesis through Control of CD4+ T-Cell Responses{triangledown}

David A. Leib,1,2* Diane E. Alexander,1 Douglas Cox,1 Jiyi Yin,1 and Thomas A. Ferguson1

Departments of Ophthalmology and Visual Sciences,1 Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 631102

Received 10 August 2009/ Accepted 9 September 2009

Autophagy is an important component of host innate and adaptive immunity to viruses. It is critical for the degradation of intracellular pathogens and for promoting antigen presentation. Herpes simplex virus type 1 (HSV-1) infection induces an autophagy response, but this response is antagonized by the HSV-1 neurovirulence gene product, ICP34.5. This is due, in part, to its interaction with the essential autophagy protein Beclin 1 (Atg6) via the Beclin-binding domain (BBD) of ICP34.5. Using a recombinant virus lacking the BBD, we examined pathogenesis and immune responses using mouse models of infection. The BBD-deficient virus ({Delta}68H) replicated equivalently to its marker-rescued counterpart ({Delta}68HR) at early times but was cleared more rapidly than {Delta}68HR from all tissues at late times following corneal infection. In addition, the infection of the cornea with {Delta}68H induced less ocular disease than {Delta}68HR. These results suggested that {Delta}68H was attenuated due to its failure to control adaptive rather than innate immunity. In support of this idea, {Delta}68H stimulated a significantly stronger CD4+ T-cell-mediated delayed-type hypersensitivity response and resulted in significantly more production of gamma interferon and interleukin-2 from HSV-specific CD4+ T cells than {Delta}68HR. Taken together, these data suggest a role for the BBD of ICP34.5 in precluding autophagy-mediated class II antigen presentation, thereby enhancing the virulence and pathogenesis of HSV-1.

* Corresponding author. Present address: Department of Microbiology and Immunology, Dartmouth-Hitchcock Medical Center, 630E Borwell Bldg., HB 7556, 1 Medical Center Dr., Lebanon, NH 03756. Phone: (603) 650-8616. Fax: (603) 650-6223. E-mail: David.A.Leib{at}Dartmouth.edu

{triangledown} Published ahead of print on 14 October 2009.

Journal of Virology, December 2009, p. 12164-12171, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01676-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»