scholarly journals Envelope Proteins of Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Induce Similar Bronchioalveolar Tumors in Lungs of Mice

2006 ◽  
Vol 80 (18) ◽  
pp. 9322-9325 ◽  
Author(s):  
Sarah K. Wootton ◽  
Christine L. Halbert ◽  
A. Dusty Miller
Keyword(s):  
Airway Epithelial Cells ◽  
Tumor Formation ◽  
Airway Epithelial ◽  
Jaagsiekte Sheep Retrovirus ◽  
Sheep And Goats ◽  
Specific Tumor ◽  
Enzootic Nasal Tumor Virus ◽  
Tumor Virus ◽  
Nasal Tumor ◽  
Env Protein

ABSTRACT Jaagsiekte sheep retrovirus (JSRV) induces bronchioalveolar tumors in sheep and goats. Expression of the JSRV envelope (Env) protein in mouse airway epithelial cells induces similar tumors, indicating that Env expression is sufficient for tissue-specific tumor formation. Enzootic nasal tumor virus (ENTV) is related to JSRV but induces tumors in the nasal epithelium of sheep and goats. Here we found that ENTV Env can also induce tumors in mice but, unexpectedly, with a phenotype identical to that of tumors induced by the JSRV Env, indicating that factors other than Env mediate the tissue specificity of tumor induction by ENTV.

scholarly journals The U3 and Env Proteins of Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Both Contribute to Tissue Tropism

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1061 ◽  
Author(s):  
Rosales Gerpe ◽  
van Lieshout ◽  
Domm ◽  
Ingrao ◽  
Datu ◽  
...  
Keyword(s):  
Amino Acid Identity ◽  
Tissue Tropism ◽  
Genetic Determinants ◽  
Tissue Slices ◽  
Jaagsiekte Sheep Retrovirus ◽  
Nasal Turbinate ◽  
Show Evidence ◽  
Enzootic Nasal Tumor Virus ◽  
Tumor Virus ◽  
Nasal Tumor

Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are small-ruminant betaretroviruses that share high nucleotide and amino acid identity, utilize the same cellular receptor, hyaluronoglucosaminidase 2 (Hyal2) for entry, and transform tissues with their envelope (Env) glycoprotein; yet, they target discrete regions of the respiratory tract—the lung and nose, respectively. This distinct tissue selectivity makes them ideal tools with which to study the pathogenesis of betaretroviruses. To uncover the genetic determinants of tropism, we constructed JSRV–ENTV chimeric viruses and produced lentivectors pseudotyped with the Env proteins from JSRV (Jenv) and ENTV (Eenv). Through the transduction and infection of lung and nasal turbinate tissue slices, we observed that Hyal2 expression levels strongly influence ENTV entry, but that the long terminal repeat (LTR) promoters of these viruses are likely responsible for tissue-specificity. Furthermore, we show evidence of ENTV Env expression in chondrocytes within ENTV-infected nasal turbinate tissue, where Hyal2 is highly expressed. Our work suggests that the unique tissue tropism of JSRV and ENTV stems from the combined effort of the envelope glycoprotein-receptor interactions and the LTR and provides new insight into the pathogenesis of ENTV.

scholarly journals Improved Enzootic Nasal Tumor Virus Pseudotype Packaging Cell Lines Reveal Virus Entry Requirements in Addition to the Primary Receptor Hyal2

2005 ◽  
Vol 79 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Neal S. Van Hoeven ◽  
A. Dusty Miller
Keyword(s):  
Cell Lines ◽  
High Titer ◽  
Surface Protein ◽  
Retroviral Vectors ◽  
Epithelial Cancers ◽  
Wide Range ◽  
Enzootic Nasal Tumor Virus ◽  
Tumor Virus ◽  
Nasal Tumor ◽  
Env Protein

ABSTRACT Enzootic nasal tumor virus (ENTV) and jaagsiekte sheep retrovirus (JSRV) are closely related retroviruses that cause epithelial cancers of the respiratory tract in sheep and goats. Both viruses use the glycosylphosphatidylinositol (GPI)-anchored cell surface protein hyaluronidase 2 (Hyal2) as a receptor for cell entry, and entry is mediated by the envelope (Env) proteins encoded by these viruses. Retroviral vectors bearing JSRV Env can transduce cells from a wide range of species, with the exception of rodent cells. Because of the low titer of vectors bearing ENTV Env, it has been difficult to determine the tropism of ENTV vectors, which appeared to transduce cells from sheep and humans only. Here we have developed high-titer ENTV packaging cells and confirm that ENTV has a restricted host range compared to that of JSRV. Most cells that are not transduced by JSRV or ENTV vectors can be made susceptible following expression of human Hyal2 on the cells. However, five rat cell lines from different rat strains and different tissues that were engineered to express human Hyal2 were still only poorly infected by ENTV vectors, even though the ENTV Env protein could bind well to human Hyal2 expressed on four of these cell lines. These results indicate the possibility of a coreceptor requirement for these viruses.

scholarly journals Bronchioloalveolar Carcinoma Not Related to Jaagsiekte Sheep Retrovirus in a Goat

2007 ◽  
Vol 44 (5) ◽  
pp. 710-712 ◽  
Author(s):  
A. Ortin ◽  
A. A. Benito ◽  
D. Lacasta ◽  
L. M. Ferrer ◽  
M. De Las Heras
Keyword(s):  
Lung Tumor ◽  
Clinical Signs ◽  
Bronchioloalveolar Carcinoma ◽  
Alveolar Type ◽  
Chain Reaction ◽  
Jaagsiekte Sheep Retrovirus ◽  
Enzootic Nasal Tumor Virus ◽  
Tumor Virus ◽  
Nasal Tumor ◽  
Polymerase Chain

A spontaneous lung tumor in a 5–year-old goat of the Murciano-Granadina breed is described in this paper. Clinical signs of cachexia and tachypnoea were evident, and a considerable amount of white mucous foamy fluid was discharged from the nostrils when the animal's head was lowered. A lung tumor with the characteristics of bronchioloalveolar carcinoma was detected during histopathologic examination. The tumor cells were positive for surfactant proteins C and B, confirming that alveolar type II cells were the origin of the neoplasia. Tumor samples were tested by polymerase chain reaction, immunoblotting, and immunohistochemistry for the presence of Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV), another retrovirus very closely related to JSRV, but all tests were negative. Therefore, this is the first reported case of spontaneous bronchioloalveolar carcinoma not related to JSRV or ENTV infection in a goat.

scholarly journals Enzootic Nasal Tumor Virus Envelope Requires a Very Acidic pH for Fusion Activation and Infection

2008 ◽  
Vol 82 (18) ◽  
pp. 9023-9034 ◽  
Author(s):  
Marceline Côté ◽  
Thomas J. Kucharski ◽  
Shan-Lu Liu
Keyword(s):  
Low Ph ◽  
Prolonged Treatment ◽  
Close Relative ◽  
Target Cells ◽  
Acidic Ph ◽  
Enzootic Nasal Tumor Virus ◽  
Tumor Virus ◽  
Nasal Tumor ◽  
Ph Dependent ◽  
Env Protein

ABSTRACT Enzootic nasal tumor virus (ENTV) is a close relative of jaagsiekte sheep retrovirus (JSRV), and the two viruses use the same receptor, hyaluronidase 2 (Hyal2), for cell entry. We report here that, unlike the JSRV envelope (Env) protein, the ENTV Env protein does not induce cell fusion at pHs of 5.0 and above but requires a much lower pH (4.0 to 4.5) for fusion to occur. The entry of ENTV Env pseudovirions was substantially inhibited by bafilomycin A1 (BafA1) but was surprisingly enhanced by lysosomotropic agents and lysosomal protease inhibitors following a 4- to 6-h treatment period; of note, prolonged treatment with BafA1 or ammonium chloride completely blocked ENTV entry. Unlike typical pH-dependent viruses, ENTV Env pseudovirions were virtually resistant to inactivation at a low pH (4.5 or 5.0). Using chimeras formed from ENTV and JSRV Env proteins, we demonstrated that the transmembrane (TM) subunit of ENTV Env is primarily responsible for its unusually low pH requirement for fusion but found that the surface (SU) subunit of ENTV Env also critically influences its relatively low and pH-dependent fusion activity. Furthermore, the poor infectivity of ENTV pseudovirions in human cells was significantly improved by either replacing the SU subunit of ENTV Env with that of JSRV Env or overexpressing the functional Hyal2 receptor in target cells, suggesting that ENTV SU-Hyal2 interaction is likely to be the limiting step for viral infectivity. Collectively, our data reveal that the fusogenicity of ENTV Env is intrinsically lower than that of JSRV Env and that ENTV requires a more acidic pH for fusion, which may occur in an intracellular compartment(s) distinct from that used by JSRV.

scholarly journals Complete Sequence of Enzootic Nasal Tumor Virus, a Retrovirus Associated with Transmissible Intranasal Tumors of Sheep

1999 ◽  
Vol 73 (5) ◽  
pp. 3986-3993 ◽  
Author(s):  
Christina Cousens ◽  
Esmeralda Minguijon ◽  
Robert G. Dalziel ◽  
Aurora Ortin ◽  
Mercedes Garcia ◽  
...  
Keyword(s):  
Complete Genome ◽  
Complete Sequence ◽  
Endogenous Retroviruses ◽  
Type B ◽  
Jaagsiekte Sheep Retrovirus ◽  
Genetic Organization ◽  
Enzootic Nasal Tumor Virus ◽  
Tumor Virus ◽  
Nasal Tumor

ABSTRACT The sequence of the complete genome of ovine enzootic nasal tumor virus, an exogenous retrovirus associated exclusively with contagious intranasal tumors of sheep, was determined. The genome is 7,434 nucleotides long and exhibits a genetic organization characteristic of type B and D oncoviruses. Enzootic nasal tumor virus is closely related to the Jaagsiekte sheep retrovirus and to sheep endogenous retroviruses.

scholarly journals Mechanism of Cell Entry and Transformation by Enzootic Nasal Tumor Virus

2002 ◽  
Vol 76 (5) ◽  
pp. 2141-2149 ◽  
Author(s):  
Clarissa Dirks ◽  
Fuh-Mei Duh ◽  
Sharath K. Rai ◽  
Michael I. Lerman ◽  
A. Dusty Miller
Keyword(s):  
Virus Entry ◽  
Regulatory Elements ◽  
Infected Sheep ◽  
Cell Entry ◽  
Cell Surface Receptor ◽  
Viral Gene ◽  
Enzootic Nasal Tumor Virus ◽  
Tumor Virus ◽  
Nasal Tumor ◽  
Env Protein

ABSTRACT Enzootic nasal tumor virus (ENTV) induces nasal epithelial cancer in infected sheep, but it is a simple retrovirus lacking a known oncogene. ENTV is closely related to jaagsiekte sheep retrovirus (JSRV), which also causes cancer in sheep but in the epithelial cells of the lower airways and alveoli. Here we show that as with JSRV, the envelope (Env) protein of ENTV can transform cultured cells and thus is likely to be responsible for oncogenesis in animals. In addition, the ENTV Env protein mediates virus entry using the same receptor as does JSRV Env, the candidate tumor suppressor Hyal2. However, ENTV Env mediates entry into cells from a more restricted range of species than does JSRV, and based on this finding we have identified amino acid regions in the Env proteins that are important for virus entry. Also, because ENTV does not efficiently use human Hyal2 as a receptor, we cloned the ovine Hyal2 cDNA and show that the encoded protein functions as an efficient receptor for both ENTV and JSRV. In summary, although ENTV and JSRV use the same cell surface receptor for cell entry and apparently transform cells by the same mechanism, they induce cancer in different tissues of infected sheep, indicating that oncogenesis is regulated at some other level. The transcriptional regulatory elements in these viruses are quite different, indicating that tissue-specific oncogenesis is likely regulated at the level of viral gene expression.

scholarly journals Nasal adenocarcinoma associated with jaagsiekte sheep retrovirus infection in a sheep

2019 ◽  
Vol 32 (1) ◽  
pp. 152-155 ◽  
Author(s):  
Hanne Jahns ◽  
Chris Cousens
Keyword(s):  
Animal Health ◽  
Health Impact ◽  
Jaagsiekte Sheep Retrovirus ◽  
Enzootic Nasal Tumor Virus ◽  
Microscopic Features ◽  
Tumor Virus ◽  
Nasal Tumor ◽  
Nasal Adenocarcinoma ◽  
Anatomic Locations ◽  
Retrovirus Infection

Betaretrovirus-induced transmissible respiratory tumors in sheep arise at 2 distinct anatomic locations, either deep in the lung tissue caused by jaagsiekte sheep retrovirus (JSRV) or in the nasal cavity induced by ovine enzootic nasal tumor virus (ENTV-1). JSRV and ENTV-1 are found in many countries worldwide and have a significant economic and animal health impact. Although JSRV is endemic in sheep in the British Isles, ENTV-1 has not been reported. We report herein a nasal adenocarcinoma in a cull 8-y-old Belclare ewe from Ireland. The gross and microscopic features and immunohistochemistry results were consistent with an ENTV-1–associated tumor. However, differential PCR, using primers specific to regions of divergent sequence between the viruses, was performed on different parts of the adenocarcinoma and produced consistent results: positive for JSRV and negative for ENTV-1. An association of JSRV with nasal adenocarcinoma in sheep has not been reported previously, to our knowledge. Our case shows the necessity of using PCR in combination with immunohistochemistry to reach an accurate etiologic diagnosis, which is of importance in countries currently free of ENTV-1.

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