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Proceedings of the National Academy of... Sep 1967
Topics: Avian Leukosis Virus; Avian Sarcoma Viruses; Centrifugation, Density Gradient; Helper Viruses; Leukemia Virus, Murine; Mammary Tumor Virus, Mouse; Nucleoproteins; Phosphorus Isotopes; RNA, Viral; Tritium; Ultracentrifugation; Uridine
PubMed: 4293266
DOI: 10.1073/pnas.58.3.825 -
Comparative Medicine Feb 2020Despite the lack of confirmed reports of an exogenous Simian betaretrovirus (SRV) isolated from baboons ( sp.), reports of simian endogenous gammaretrovirus (SERV) in...
Despite the lack of confirmed reports of an exogenous Simian betaretrovirus (SRV) isolated from baboons ( sp.), reports of simian endogenous gammaretrovirus (SERV) in baboons with complete genomes suggest that such viruses may be potentially infectious. In addition, serologic tests have repeatedly demonstrated antibody reactivity to SRV in baboons from multiple colonies. These findings complicate the management and use of such animals for research. To provide further insight into this situation, we performed in vitro and in vivo studies to determine if baboons are or can be infected with SRV. In our initial experiment, we were not able to isolate SRV from 6 seropositive or sero-indeterminate baboons by coculturing their peripheral blood mononuclear cells (PBMC) with macaque PBMC or permissive cell lines. In a subsequent experiment, we found that baboon PBMC infected in vitro with high dose SRV were permissive to virus replication. To test in vivo infectibil- ity, groups of naive baboons were infused intravenously with either (i) the same SRV tissue culture virus stocks used for the in vitro studies, (ii) SRV antibody positive and PCR positive macaque blood, (iii) SRV antibody positive or indeterminate, but PCR negative baboon blood, or (iv) SRV antibody and PCR negative baboon blood. Sustained SRV infection, as defined by reproducible PCR detection and/or antibody seroconversion, was confirmed in 2 of 3 baboons receiving tissue culture virus but not in any recipients of transfused blood from seropositive macaques or baboons. In conclusion, the data indicate that even though baboon cells can be infected experimentally with high doses of tissue culture grown SRV, baboons that are repeatedly SRV antibody positive and PCR negative are unlikely to be infected with exogenous SRV and thus are unlikely to transmit a virus that would threaten the SPF status of captive baboon colonies.
Topics: Animals; Betaretrovirus; Female; Leukocytes, Mononuclear; Male; Monkey Diseases; Papio; Retroviridae Infections; Virus Replication
PubMed: 31747991
DOI: 10.30802/AALAS-CM-19-000014 -
Cellular and Molecular Life Sciences :... Nov 2008Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. Jaagsiekte sheep retrovirus (JSRV) is a... (Review)
Review
Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. Jaagsiekte sheep retrovirus (JSRV) is a pathogenic exogenous retrovirus and the causative agent of ovine pulmonary adenocarcinoma. The sheep genome contains at least 27 copies of endogenous retroviruses (enJSRVs) highly related to JSRV. enJSRVs have played several roles in the evolution of the domestic sheep as they are able to block the JSRV replication cycle and play a critical role in sheep conceptus development and placental morphogenesis. Available data strongly suggest that some dominant negative enJSRV proviruses (i.e. able to block JSRV replication) have been positively selected during evolution. Interestingly, viruses escaping the transdominant enJSRV loci have recently emerged (less than 200 years ago). Thus, endogenization of these retroviruses may still be occurring today. Therefore, sheep provide an exciting and unique system to study retrovirus-host coevolution. (Part of a multi-author review).
Topics: Amino Acid Sequence; Animals; Betaretrovirus; Cell Transformation, Viral; Embryonic Development; Evolution, Molecular; Female; Gene Expression Regulation, Viral; Genes, Viral; Host-Pathogen Interactions; Models, Molecular; Molecular Sequence Data; Morphogenesis; Placenta; Placentation; Pregnancy; Protein Conformation; Proviruses; Pulmonary Adenomatosis, Ovine; Retroviridae Infections; Retroviridae Proteins, Oncogenic; Selection, Genetic; Sequence Alignment; Sequence Homology, Amino Acid; Sheep; Sheep Diseases; Species Specificity; Tumor Virus Infections; Viral Interference
PubMed: 18818869
DOI: 10.1007/s00018-008-8500-9 -
Viruses Jun 2018The mouse mammary tumor virus (MMTV) Pr77 polypeptide is an essential retroviral structural protein without which infectious viral particles cannot be formed. This...
The mouse mammary tumor virus (MMTV) Pr77 polypeptide is an essential retroviral structural protein without which infectious viral particles cannot be formed. This process requires specific recognition and packaging of dimerized genomic RNA (gRNA) by Gag during virus assembly. Most of the previous work on retroviral assembly has used either the nucleocapsid portion of Gag, or other truncated Gag derivatives—not the natural substrate for virus assembly. In order to understand the molecular mechanism of MMTV gRNA packaging process, we expressed and purified full-length recombinant Pr77-His₆-tag fusion protein from soluble fractions of bacterial cultures. We show that the purified Pr77-His₆-tag protein retained the ability to assemble virus-like particles (VLPs) in vitro with morphologically similar immature intracellular particles. The recombinant proteins (with and without His₆-tag) could both be expressed in prokaryotic and eukaryotic cells and had the ability to form VLPs in vivo. Most importantly, the recombinant Pr77-His₆-tag fusion proteins capable of making VLPs in eukaryotic cells were competent for packaging sub-genomic MMTV RNAs. The successful expression and purification of a biologically active, full-length MMTV Pr77 should lay down the foundation towards performing RNA–protein interaction(s), especially for structure-function studies and towards understanding molecular intricacies during MMTV gRNA packaging and assembly processes.
Topics: Escherichia coli; Gene Expression; Gene Products, gag; HEK293 Cells; Humans; Mammary Tumor Virus, Mouse; Protein Binding; RNA, Viral; Recombinant Proteins; Virosomes; Virus Assembly
PubMed: 29912170
DOI: 10.3390/v10060334 -
Animal Reproduction Science Sep 2012Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted... (Review)
Review
Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. The sheep genome contains 27 JSRV-related endogenous betaretroviruses (enJSRVs) related to the pathogenic Jaagsiekte sheep retrovirus (JSRV) that have been integrating in the host genome for the last 5-7 million years. The exogenous JSRV is a causative agent of a transmissible lung cancer in sheep, and enJSRVs are able to protect the host against JSRV infection. In sheep, the enJSRVs are most abundantly expressed in the uterine epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm. Sixteen of the 27 enJSRV loci contain an envelope (env) gene with an intact open reading frame, and in utero loss-of-function experiments found the enJSRVs Env to be essential for trophoblast outgrowth and conceptus elongation. Collectively, available evidence supports the ideas that genes captured from ancestral retroviruses were pivotal in the acquisition of new, important functions in mammalian evolution and were positively selected for biological roles in genome plasticity, protection of the host against infection of related pathogenic and exogenous retroviruses, and a convergent physiological role in placental morphogenesis and thus mammalian reproduction. The discovery of ERVs in mammals was initially based on molecular cloning discovery techniques and will be boosted forward by next generation sequencing technologies and in silico discovery techniques.
Topics: Animals; Biological Evolution; Endogenous Retroviruses; Gene Expression Regulation, Developmental; Genome; Jaagsiekte sheep retrovirus; Sheep
PubMed: 22951118
DOI: 10.1016/j.anireprosci.2012.08.016 -
Viruses Sep 2010Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal... (Review)
Review
Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal model for the study of human breast cancer. Like other complex retroviruses, MMTV encodes a number of accessory proteins that both facilitate infection and affect host immune response. In vivo, the virus predominantly infects lymphocytes and mammary epithelial cells. High level infection of mammary epithelial cells ensures efficient passage of virus to the next generation. It also results in mammary tumor induction, since the MMTV provirus integrates into the mammary epithelial cell genome during viral replication and activates cellular oncogene expression. Thus, mammary tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer.
Topics: Animals; Cell Transformation, Viral; Epithelial Cells; Lymphocytes; Mammary Tumor Virus, Mouse; Retroviridae Infections; Tumor Virus Infections; Viral Proteins; Virulence Factors
PubMed: 21274409
DOI: 10.3390/v2092000 -
Breast Cancer Research : BCR 2000
Review
Topics: Animals; Cell Cycle; Disease Models, Animal; Female; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Mice, Knockout; Mice, Transgenic; Signal Transduction
PubMed: 11250684
DOI: 10.1186/bcr20 -
Journal of Animal Science Aug 2021Ovarian paracrine mediation by components of the wingless-type mouse mammary tumor virus integration site ligands (WNT1 to 11) and their receptors, frizzled family...
Ovarian paracrine mediation by components of the wingless-type mouse mammary tumor virus integration site ligands (WNT1 to 11) and their receptors, frizzled family members (FZD1 to 10), has been proposed. Secreted truncated forms of FZD proteins (e.g., secreted frizzled-related protein 4 [SFRP4]) block the action of WNT ligands. Dickkopf-1 (DKK1) is another WNT antagonist, and R-spondin-1 (RSPO1) is one of a group of four secreted proteins that enhance WNT/β-catenin signaling. Our hypothesis was that granulosa cells signal theca cells (TCs) via SFRP4, DKK1, RSPO1, and WNT secretion to regulate TC differentiation and proliferation. Therefore, in vitro experiments were conducted to study the effects of WNT family member 3A (WNT3A), WNT5A, RSPO1, DKK1, insulin-like growth factor 1 (IGF1), bone morphogenetic protein 7 (BMP7), Indian hedgehog (IHH), and fibroblast growth factor 9 (FGF9) on bovine TC proliferation and steroidogenesis. TCs of large (8 to 20 mm) and small (3 to 6 mm) follicles were collected from bovine ovaries; TC monolayers were established in vitro and treated with various doses of recombinant human WNT3A, WNT5A, RSPO1, DKK1, IGF1, FGF9, BMP7, IHH, and/or ovine luteinizing hormone (LH) in serum-free medium for 48 h. In experiment 1, using LH-treated TC, IGF1, IHH, and WNT3A increased (P < 0.05) cell numbers and androstenedione production, whereas WNT3A and BMP7 inhibited (P < 0.05) progesterone production. In experiment 2, FGF9 blocked (P < 0.05) the WNT3A-induced increase in androstenedione production in LH plus IGF1-treated TC. In experiment 3, RSPO1 further increased (P < 0.05) LH plus IGF1-induced progesterone and androstenedione production. In experiment 4, SFRP4 and DKK1 alone had no significant effect on TC proliferation or progesterone production of large-follicle TC but both blocked the inhibitory effect of WNT5A on androstenedione production. In contrast, DKK1 alone inhibited (P < 0.05) small-follicle TC androstenedione production whereas SFRP4 was without effect. We conclude that the ovarian TC WNT system is functional in cattle, with WNT3A increasing proliferation and androstenedione production of TC.
Topics: Androstenedione; Animals; Cattle; Cells, Cultured; Female; Granulosa Cells; Hedgehog Proteins; Humans; Mammary Tumor Virus, Mouse; Mice; Ovarian Follicle; Progesterone; Sheep; Theca Cells
PubMed: 34166505
DOI: 10.1093/jas/skab197 -
Viruses Jan 2023Jaagsiekte retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma (OPA) is an important ovine respiratory disease in Switzerland. Furthermore, ovine lungs with OPA...
Jaagsiekte retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma (OPA) is an important ovine respiratory disease in Switzerland. Furthermore, ovine lungs with OPA frequently exhibited lesions suggestive of maedi-visna virus (MVV) or caprine arthritis encephalitis virus (CAEV) infection, indicating that co-morbidities might occur. Lungs and pulmonary lymph nodes were sampled from suspected OPA cases, inflammatory lung lesions and control lungs (total of 110 cases). Tissues were (a) processed for histology and immunohistochemistry (IHC), and (b) underwent DNA extraction and real-time PCR for JSRV, MVV and CAEV. Peptide sequences were used to generate virus-specific customized polyclonal antibodies. PCR-positive OPA cases and formalin-fixed and paraffin-embedded MVV- and CAEV-infected synovial cell pellets served as positive controls. Fifty-two lungs were histologically diagnosed with OPA. Histological evidence of MVV/CAEV infection was detected in 25 lungs. JSRV was detected by PCR in 84% of the suspected OPA cases; six were co-infected with MVV and one with CAEV. MVV was detected by PCR in 14 cases, and four lungs were positive for CAEV. Three lungs had MVV/CAEV co-infection. In IHC, JSRV was detected in 91% of the PCR-positive cases, whereas MVV and CAEV immunoreactivity was seen in all PCR-positive lungs. Although PCR showed a higher sensitivity compared to IHC, the combined approach allows for investigations on viral cell tropism and pathogenic processes in co-morbidities, including their potential interdependency. Furthermore, an immunohistochemical tool for specific differentiation of MVV and/or CAEV infection was implemented.
Topics: Sheep; Animals; Retroviridae; Coinfection; Ruminants; Retroviridae Infections; Antibodies; Arthritis-Encephalitis Virus, Caprine; Jaagsiekte sheep retrovirus; Real-Time Polymerase Chain Reaction
PubMed: 36851589
DOI: 10.3390/v15020376 -
The Journal of General Virology Jan 2004The endogenous betaretroviruses of small ruminants offer an excellent model to investigate the biological relevance of endogenous retroviruses (ERVs). Approximately... (Review)
Review
The endogenous betaretroviruses of small ruminants offer an excellent model to investigate the biological relevance of endogenous retroviruses (ERVs). Approximately twenty copies of endogenous betaretroviruses (enJSRVs) are present in the genome of sheep and goats. enJSRVs are highly related to Jaagsiekte sheep retrovirus (JSRV) and the Enzootic nasal tumour virus (ENTV), the causative agents of naturally occurring carcinomas of the respiratory tract of sheep. enJSRVs interact/interfere at different levels both with the host and with their exogenous and pathogenic counterparts. enJSRVs blocks the exogenous JSRV replication by a novel two-step interference mechanism acting both early and late during the virus replication cycle. enJSRVs are highly active, they are abundantly and specifically expressed in the epithelium of most of the ovine female reproductive tract. The specific spatial and temporal expression of enJSRVs supports a role in trophoblast development and differentiation as well as conceptus implantation. In addition, enJSRVs are expressed during fetal ontogeny leading to the apparent tolerance of sheep towards the pathogenic JSRV. Thus, the sheep/enJSRVs system is a model that can be utilized to study many different aspects of ERVs and retrovirus biology. The impressive technologies developed to study the sheep reproductive biology, in conjunction with the knowledge gained on the molecular biology of enJSRVs, makes the ovine system an ideal model to design experiments that can functionally address the role of ERVs in mammalian physiology.
Topics: Adaptation, Physiological; Animals; Betaretrovirus; Endogenous Retroviruses; Female; Goats; Jaagsiekte sheep retrovirus; Sheep; Uterus; Viral Interference; Virus Replication
PubMed: 14718613
DOI: 10.1099/vir.0.19547-0