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J. Cell Biol., Volume 139, Number 4, November 17, 1997 865-873

The Testicular Antiviral Defense System: Localization, Expression, and Regulation of 2'5' Oligoadenylate Synthetase, Double-Stranded RNA-activated Protein Kinase, and Mx Proteins in the Rat Seminiferous Tubule

Nathalie Dejucq,* Suzanne Chousterman,Dagger and Bernard Jégou*

* Groupe d'Etude de la Reproduction chez le Mâle-Institut National de la Santé et de la Recherche Medicale, Unité 435, Université de Rennes I, Campus de Beaulieu, 35 042 Rennes Cedex, Bretagne, France; and Dagger  Institut National de la Santé et de la Recherche Medicale, Unité 417, Hôpital St Antoine, 75 571 Paris, Cedex 12, France

Although the involvement of viruses in alterations of testicular function and in sexually transmitted diseases is well known, paradoxically, the testicular antiviral defense system has virtually not been studied. The well known antiviral activity of interferons (IFNs) occurs via the action of several IFN-induced proteins, among which the 2'5' oligoadenylate synthetase (2'5' A synthetase), the double-stranded RNA-activated protein kinase (PKR), and the Mx proteins are the best known. To explore the antiviral capacity of the testis and to study the testicular action of IFNs, we looked for the presence and regulation of these three proteins in isolated seminiferous tubule cells, cultured in the presence or in the absence of IFN alpha , IFN gamma , or Sendai virus. In all conditions tested, the meiotic pachytene spermatocytes and the post-meiotic early spermatids lacked 2'5' A synthetase, PKR, and Mx mRNAs and proteins. In contrast, Sertoli cells constitutively expressed these mRNAs and proteins, and their levels were greatly increased after IFN alpha  or Sendai virus exposure. While peritubular cells were also able to markedly express 2'5' A synthetase, PKR, and Mx mRNA and proteins after IFN alpha  or viral exposure, only PKR was constitutively present in these cells. Interestingly, IFN gamma  had no effect on peritubular cells' 2'5' A synthetase and Mx production but it enhanced Mx proteins in Sertoli cells. In conclusion, this study reveals that the seminiferous tubules are particularly well equipped to react to a virus attack. The fact that the two key tubular elements of the blood-testis barrier, namely, Sertoli and peritubular cells, were found to assume this protection allows the extension of the concept of blood-testis barrier to the testicular antiviral defense.


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