Characterization of the antiviral activity constitutively produced by murine conceptuses: Absence of placental mrnas for interferon alpha and beta

Abstract

Antiviral activity has been found in conceptus and placental tissues in numerous species, including mice, pigs, sheep, cattle and humans. In sheep and cattle, the antiviral activity is due to an interferon alpha (IFN-alpha), but in other species the nature of the protein(s) responsible for placental activity is unknown. The objectives of this study were to determine if the constitutive antiviral activity associated with the mouse conceptus is produced as early as the peri-implantation period, and to determine if the activity is due to an IFN-alpha or -beta. Conceptus and placental tissue explants released antiviral activity from Day 4 through at least Day 16 of gestation as measured in an agar overlay bioassay employing CHO cells challenged with vesicular stomatitis virus. This activity was neutralized by antiserum against MuIFN-alpha/beta. The same antiserum failed, however, to immunoprecipitate radiolabeled proteins from medium collected from Day 4 blastocysts cultured in the presence of L-[35S]-methionine. S1 nuclease analysis of placental RNA and screening of ectoplacental cone and extraembryonic ectoderm cDNA libraries with MuIFN-alpha and -beta probes failed to detect IFN related mRNAs, even under relatively non-stringent conditions of hybridization. Thus, while antiviral activity is produced by peri-implantation conceptuses in several diverse mammalian species, it does not appear to be due to a conserved type of IFN in all these species.

Gene expression during preimplantation mouse development.

“…IFN-~ is also expressed in the mouse blastocyst (Table 4; Fig. 1 ), consistent with the observation that the mouse blastocyst secretes a factor with IFN-like antiviral activity in vitro (Cross et al 1990;Nieder 1990). A member of the IFN-~ gene family was identified previously as one of the major proteins expressed by bovine, ovine, caprine, and porcine blastocysts (Imakawa et al 1987Hansen et al 1988;Cross and Roberts 1989;Roberts et al 1989;Baumbach et al 1990).…”

Constitutive and trophoblast-specific expression of a class of bovine interferon genes.

“…IFN production by human placental tissues has been widely reported (1), and suggestions of a human placental-specific IFN have been made (47)(48)(49). Antiviral activity suggestive of IFN is associated with the conceptus and placenta in mice (50,51), hamsters (52), and pigs (27). However, the overall amounts of IFN produced in these species are far lower than TP-1 production by early ruminant conceptuses, and we have been unable to detect TP-1-related mRNA in human, mouse, and pig conceptus tissues (ref.…”

Differential constitutive expression of interferon genes in early mouse embryos

“…However, we cannot exclude the possibility that similar factors may participate in the regulation of this constitutive text, and source references are for IFN-a, IFN-p, IKF-1, and IRF-2, this work for APP (amyloid precursor protein;Fisher et al, 1991); for hsp 68 (Bensaude et al, 1983 and this work); for PDGF-A, TGF-a, EGF, bFGF, NGF, G-CSF, and TGF-61 (Rappolee et al, 1988); for IL-1-7 (interleukins) and IFN-y (Rothstein et al, 1992); for Oct 1-6 (octamer-binding factors; Scholer et al, 1989Scholer et al, , 1990Rosner et al, 1991a,b). transcription. A constitutive IFN activity was also reported before by Barlow et al (1984) in 13 day post coitum (dpc) mouse embryos and by Cross et al (1990) and Nieder (1990) in mouse blastocysts.…”