Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Jan;77(1):749-53.
doi: 10.1128/jvi.77.1.749-753.2003.

Receptor usage and fetal expression of ovine endogenous betaretroviruses: implications for coevolution of endogenous and exogenous retroviruses

Thomas E Spencer  1 , Manuela Mura, C Allison Gray, Philip J Griebel, Massimo Palmarini
Affiliations

Receptor usage and fetal expression of ovine endogenous betaretroviruses: implications for coevolution of endogenous and exogenous retroviruses

Thomas E Spencer et al. J Virol. 2003 Jan.

Abstract

Betaretroviruses of sheep include two exogenous viruses, Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV), and a group of endogenous viruses known as enJSRVs. The exogenous JSRV and ENTV are the etiological agents of ovine pulmonary adenocarcinoma (OPA) and enzootic nasal tumor (ENT), respectively. Sheep affected by OPA or ENT do not show an appreciable antibody response to JSRV or ENTV. Consequently, it is conceivable that enJSRV expression in the fetal lamb tolerizes sheep to the related exogenous viruses. In this study, possible mechanisms of interference between the sheep exogenous and endogenous betaretroviruses were investigated. In situ hybridization detected enJSRV RNAs in lymphoid cells associated with the lamina propria of the small intestine and in the thymus of sheep fetuses. Low-level expression of enJSRVs was also detected in the lungs. In addition, expression of enJSRVs was found to block entry of the exogenous JSRV, presumably via mechanisms of receptor interference. Indeed, enJSRVs, like JSRV and ENTV, were found to utilize hyaluronidase-2 as a cellular receptor.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
In situ hybridization analysis of enJSRV mRNA expression in Peyer's patch tissue collected from the small intestine of fetal lambs (gestation day 120). Cross sections of different regions of the small intestine from sheep fetuses were hybridized with α-35S-labeled antisense ovine enJSRV cRNA probes. Protected transcripts were visualized by liquid emulsion autoradiography for 1 week and imaged under bright-field or dark-field illumination. (A) Bright field of jejunal Peyer's patch tissue stained with hematoxylin. Numerous lymphoid aggregates (L) are visible between the muscolaris externa (M) and the overlying mucosal epithelium (V). Domes (D) are also visible. (B) In situ hybridization reveals a high degree of enJSRV expression that localizes to cells within the lymphoid aggregates of the jejunal Peyer's patches. (C) Bright field of ileal Peyer's patch tissue stained with hematoxylin. Small lymphoid aggregates are visible between the muscularis externa (M) and the overlying mucosal epithelium (V). (D) In situ hybridization reveals enJSRV RNA expression that is localized to cells within the lymphoid aggregates of the Peyer's patch. Bar, 150 μm.
FIG. 2.
FIG. 2.
In situ hybridization analysis of enJSRV mRNA expression in the fetal thymus and lung. Cross sections of the thymus (A and B) and lung (C to F) from sheep fetuses were hybridized with α-35S-labeled antisense (A to D) or sense (E and F) ovine enJSRV cRNA probes. Protected transcripts were visualized by liquid emulsion autoradiography for 1 week and imaged under bright-field or dark-field illumination. Signals above background for enJSRVs were localized in the medulla of the thymus (B) and in the bronchiolar epithelium of the lungs (D). Bar, 75 μm.
FIG. 3.
FIG. 3.
Entry assays employing MLV-luciferase vectors pseudotyped with the JSRV Env. Values are expressed in relative light units; threefold dilutions were used in this experiment. The values are averages of duplicate experiments for each dilution. The figure shows the vector entering ST cells, while values only barely above background were found in LE cells. The experiment was repeated twice with a different DNA plasmid preparation and gave essentially the same results (data not shown).
FIG. 4.
FIG. 4.
Entry assays employing MLV-luciferase vectors pseudotyped with the JSRV (continuous line) or the enJSRV Env (broken line). Values are expressed in relative light units; threefold dilutions were used in this experiment. The values are averages of duplicate experiments for each dilution. Both the JSRV and the enJSRV vector enter NIH 3T3 cells expressing Hyal-2 but do not enter NIH 3T3 cells. The enJSRV envelope is able to transduce sheep (ST) and human (293T) cells, behaving like the exogenous JSRV. These experiments were repeated with a different DNA plasmid preparation and gave essentially the same results (data not shown).
FIG. 5.
FIG. 5.
Proposed model for sheep betaretrovirus evolution. The extensive expression of enJSRVs in the genital tract suggests that at least some of the ancestral exogenous forms of ovine betaretroviruses (“pre-JSRV”) may have been transmitted from sheep to sheep through coitus. Subsequent to becoming endogenous, the selection of respiratory tract-tropic exogenous betaretroviruses (like the current JSRV and ENTV) might have been favored by interference processes given by the expression of enJSRVs in the epithelium of the genital tract. Sheep shown in black represent sheep before the fixation of enJSRVs in their germ line. The time of endogenization shown in the figure reflects what has been estimated for the three known full-length enJSRV loci (21) and is not necessarily representative of all the enJSRV loci present in the sheep genome.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alberti, A., C. Murgia, S.-L. Liu, M. Mura, C. Cousens, J. M. Sharp, A. D. Miller, and M. Palmarini. 2002. Envelope-induced cell transformation by ovine betaretroviruses. J. Virol. 76:5387-5394. - PMC - PubMed
    1. Best, S., P. R. Le Tissier, and J. P. Stoye. 1997. Endogenous retroviruses and the evolution of resistance to retroviral infection. Trends Microbiol. 5:313-318. - PubMed
    1. Bock, M., and J. P. Stoye. 2000. Endogenous retroviruses and the human germline. Curr. Opin. Genet. Dev. 10:651-655. - PubMed
    1. Boeke, J. D., and J. P. Stoye. 1997. Retrotransposons, endogenous retroviruses and the evolution of retroelements, p. 343-436. In J. M. Coffin, S. H. Hughes, and H. E. Varmus (ed.), Retroviruses. Cold Spring Harbor Laboratory Press, Plainview, N.Y. - PubMed
    1. Cousens, C., E. Minguijon, R. G. Dalziel, A. Ortin, M. Garcia, J. Park, L. Gonzalez, J. M. Sharp, and M. de las Heras. 1999. Complete sequence of enzootic nasal tumor virus, a retrovirus associated with transmissible intranasal tumors of sheep. J. Virol. 73:3986-3993. - PMC - PubMed

Publication types

LinkOut - more resources