Expression of Endogenous Betaretroviruses in the Ovine Uterus: Effects of Neonatal Age, Estrous Cycle, Pregnancy, and Progesterone

Abstract

The ovine genome contains 15 to 20 copies of endogenous retroviruses (enJSRVs) highly related to the oncogenic jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus. enJSRVs are highly expressed in the endometrial lumenal epithelia (LE) and glandular epithelia (GE) of the ovine uterus. The effects of neonatal age, estrous cycle, pregnancy, and progesterone on expression of enJSRVs in the ovine uterus were determined. Expression of enJSRV RNAs was absent from the uterus of ewes at birth, but enJSRV RNAs were expressed specifically in the LE and developing GE from postnatal day (PND) 7 to PND 56. In adult ewes, enJSRV RNAs were detected only in the epithelia of the uterine endometrium, as well as epithelia of the oviduct, cervix, and vagina. In cyclic ewes, endometrial enJSRV RNA abundance was lowest on day 1, increased 12-fold between days 1 and 13, and then decreased to day 15. In pregnant ewes, levels of endometrial enJSRV RNAs were high on day 11, increased to day 13, and then decreased to day 19. In day 17 and 19 conceptuses, enJSRV RNAs were also detected in binucleate cells of the trophectoderm. Immunoreactive JSRV capsid and envelope proteins were detected in the endometrial LE and GE, as well as in the binucleate cells of the conceptus. In transfection assays utilizing ovine endometrial LE cells, progesterone increased transcriptional activity of several enJSRV long terminal repeats. Collectively, these results indicate that transcription of enJSRVs in the endometrial epithelia of the ovine uterus is increased by progesterone and might support a role for enJSRVs in conceptus-endometrium interactions during the peri-implantation period and early placental morphogenesis.

Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep

“…Envelope proteins and env mRNA are present in the mononuclear trophoblasts and particularly abundant in the binucleate cells and the syncytiotrophoblast plaques of the ovine placenta [24,25,62]. Only low levels of expression have been described in the lung epithelium [62].…”

“…In the female genital tract, enJSRV expression is limited to the epithelia and is particularly abundant in the endometrium [22,25,26,62]. Envelope proteins and env mRNA are present in the mononuclear trophoblasts and particularly abundant in the binucleate cells and the syncytiotrophoblast plaques of the ovine placenta [24,25,62]. Only low levels of expression have been described in the lung epithelium [62].…”

Late viral interference induced by transdominant Gag of an endogenous retrovirus

“…JSRV is the causative agent of ovine pulmonary adenocarcinoma, a transmissible lung cancer of sheep (3,4). JSRV is a lung-tropic retrovirus, whereas enJSRVs are expressed at high levels in the epithelial cells of most of the genital tract of the ewe (5)(6)(7).…”

The Interferon Stimulated Genes (ISG) 17 and Mx have different temporal and spatial expression in the ovine uterus suggesting more complex regulation of the Mx gene

“…Insight into the unique regulation of Mx expression in the LE and sGE comes from a recent report that showed the presence of high levels of endogenous retroviral (enJSRV) mRNAs and capsid and envelope proteins in the ovine endometrium (Palmarini et al 2001). Expression of these enJSRVs was limited to the LE and sGE and appeared to be regulated by progesterone.…”