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The ribonucleotide reductase domain of the R1 subunit of herpes simplex virus type 2 ribonucleotide reductase is essential for R1 antiapoptotic function

Stéphane Chabaud^1,

Seyyed Mehdy Elahi^2,

¹ Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke Est, Montréal, QC H2L 4M1, Canada
² Institut de Recherche en Biotechnologie, 6100 ave Royalmount, Montréal, QC H4P 2R2, Canada
³ Département de Microbiologie et Immunologie, Université de Montréal, QC, Canada
⁴ INRS-IAF, Université du Québec, Laval, QC H7N 4Z3, Canada
⁵ Département de Médecine, Université de Montréal, QC, Canada

Correspondence
Yves Langelier
yves.langelier{at}umontreal.ca

The R1 subunit (ICP10) of herpes simplex virus type 2 (HSV-2) ribonucleotide reductase (RR), which in addition to its C-terminal reductase domain possesses a unique N-terminal domain of about 400 aa, protects cells against apoptosis. As the NH₂ domain on its own is not antiapoptotic, it has been postulated that both domains of R1 or part(s) of them could be necessary for this function. Here, N- and C-terminal deletions were introduced in HSV-2 R1 to map the domain(s) involved in its antiapoptotic potential. The results showed that, whereas most of the NH₂ domain including part of the recently described putative -crystallin domain is dispensable for antiapoptotic activity, it is the integrity of the structured RR domain that is required for protection. As the -crystallin domain appears to play an important role in protein folding and oligomerization, the N-terminal boundary of the antiapoptotic domain could not be defined precisely. In addition, this study provided evidence that overexpression of HSV-2 R2 at levels up to 30-fold more than HSV-2 R1 did not decrease protection from tumour necrosis factor alpha, indicating that the R1 surface where R2 binds is not involved in antiapoptotic activity. Importantly, this result suggests that the co-expression of both RR subunits during the lytic cycle should not affect protection from this cytokine.

Details of the construction of plasmids and viruses expressing HSV-2 R1 (strain 333) and its deletion mutants are available as supplementary material in JGV Online.

Present address: LOEX, Hôpital du Saint-Sacrement, QC G1S 4L8, Canada.

Present address: Faculté de Médecine Vétérinaire, Saint-Hyacinthe, QC J2S 7C6, Canada.

This article has been cited by other articles:

				J.-Y. Han, S. A. Miller, T. M. Wolfe, H. Pourhassan, and K. R. Jerome Cell Type-Specific Induction and Inhibition of Apoptosis by Herpes Simplex Virus Type 2 ICP10 J. Virol., March 15, 2009; 83(6): 2765 - 2769. [Abstract] [Full Text] [PDF]