This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, H. Articles by He, B. Search for Related Content PubMed PubMed Citation Articles by Jin, H. Articles by He, B.

 Previous Article  |  Next Article 

Journal of Virology, May 2009, p. 4984-4994, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02535-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The ₁34.5 Protein of Herpes Simplex Virus 1 Is Required To Interfere with Dendritic Cell Maturation during Productive Infection

Huali Jin,¹ Yijie Ma,¹ Bellur S. Prabhakar,¹ Zongdi Feng,¹ Tibor Valyi-Nagy,² Zhipeng Yan,¹ Dustin Verpooten,¹ Cuizhu Zhang,³ Youjia Cao,^3* and Bin He^1*

Department of Microbiology and Immunology,¹ Department of Pathology, College of Medicine, University of Illinois, Chicago, Illinois 60612,² Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China³

Received 9 December 2008/ Accepted 26 February 2009

The ₁34.5 protein of herpes simplex virus 1 is an essential factor for viral virulence. In infected cells, this viral protein prevents the translation arrest mediated by double-stranded RNA-dependent protein kinase R. Additionally, it associates with and inhibits TANK-binding kinase 1, an essential component of Toll-like receptor-dependent and -independent pathways that activate interferon regulatory factor 3 and cytokine expression. Here, we show that ₁34.5 is required to block the maturation of conventional dendritic cells (DCs) that initiate adaptive immune responses. Unlike wild-type virus, the ₁34.5 null mutant stimulates the expression of CD86, major histocompatibility complex class II (MHC-II), and cytokines such as alpha/beta interferon in immature DCs. Viral replication in DCs inversely correlates with interferon production. These phenotypes are also mirrored in a mouse ocular infection model. Further, DCs infected with the ₁34.5 null mutant effectively activate naïve T cells whereas DCs infected with wild-type virus fail to do so. Type I interferon-neutralizing antibodies partially reverse virus-induced upregulation of CD86 and MHC-II, suggesting that ₁34.5 acts through interferon-dependent and -independent mechanisms. These data indicate that ₁34.5 is involved in the impairment of innate immunity by inhibiting both type I interferon production and DC maturation, leading to defective T-cell activation.

---

* Corresponding author. Mailing address for Bin He: Department of Microbiology and Immunology (M/C 790), College of Medicine, The University of Illinois at Chicago, 835 South Wolcott Ave., Chicago, IL 60612. Phone: (312) 996-2391. Fax: (312) 996-6415. E-mail: tshuo{at}uic.edu. Mailing address for Youjia Cao: Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China. Phone and fax: (86-22) 23500808. E-mail: caoyj{at}nankai.edu.cn

Published ahead of print on 11 March 2009.

---

Journal of Virology, May 2009, p. 4984-4994, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02535-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Verpooten, D., Feng, Z., Valyi-Nagy, T., Ma, Y., Jin, H., Yan, Z., Zhang, C., Cao, Y., He, B. (2009). Dephosphorylation of eIF2{alpha} Mediated by the {gamma}134.5 Protein of Herpes Simplex Virus 1 Facilitates Viral Neuroinvasion. J. Virol. 83: 12626-12630 [Abstract] [Full Text]