Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jaagsiekte sheep retrovirus (JSRV) infects lung epithelial cells in sheep, and oncoretroviral vectors bearing JSRV Env can mediate transduction of human cells, suggesting that such vectors might be useful for lung-directed gene therapy. Here we show that JSRV Env can also efficiently pseudotype a human immunodeficiency virus type 1-based lentiviral vector, a more suitable vector for transduction of slowly dividing lung epithelial cells. We created several chimeric Env proteins that, unlike the parental Env, do not transform rodent fibroblasts but are still capable of pseudotyping lentiviral and oncoretroviral vectors.
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PMID:Jaagsiekte sheep retrovirus envelope efficiently pseudotypes human immunodeficiency virus type 1-based lentiviral vectors. 1496 73

Retroviral pseudotyping for gene transfer applications endeavors to alter vector tropism and maintain a suitable titer. We investigated the compatibility of the Jaagsiekte sheep retrovirus (JSRV) envelope glycoprotein with the feline immunodeficiency virus (FIV) vector. A construct consisting of the minimal JSRV env coding region expressed from a standard mammalian expression plasmid generated FIV vector titers of approximately 10(4) TU/ml following standard triple transfection, collection of supernatants, and concentration by centrifuge. Interestingly, retention of the native proviral 5' and 3' flanking regions surrounding the JSRV env resulted in exceptional titers of approximately 10(8) TU/ml following the same viral preparation. To discern the regions necessary to achieve this 10,000-fold increase in titer, additional constructs were designed and tested. Our results indicate that the enhanced vector titer correlates with an increase in steady-state levels of envelope RNA that results from a combination of RNA splicing and stability, leading to increased envelope protein production. Expression of four other glycoproteins in an expression plasmid retaining the enhancing elements from the JSRV proviral sequence increased FIV vector titers from 0- to 100-fold. These novel data demonstrate that optimization of the envelope expression construct can profoundly influence titers for lentivirus vectors.
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PMID:Inclusion of Jaagsiekte sheep retrovirus proviral elements markedly increases lentivirus vector pseudotyping efficiency. 1572 43

A feline immunodeficiency virus (FIV)-based lentiviral vector was pseudotyped to identify envelope (env) glycoproteins that direct efficient gene transfer to pulmonary epithelia for the treatment or prevention of lung diseases. The envelope glycoprotein from the Jaagsiekte sheep retrovirus (JSRV) is a candidate under investigation. We utilized high titer FIV vector (>10(8) TU/ml) pseudotyped with the JSRV env glycoprotein (JSRVFIV) to study the transduction of polarized primary cultures of human airway epithelia and receptor/vector interactions. The reported receptor for JSRV, hyaluronidase 2 (HYAL2), is a GPI-linked protein. We expressed FLAG-tagged HYAL2 in polarized airway epithelia using an adenoviral vector and documented that the HYAL2 protein sorts predominantly to the apical surface. Of interest, the efficiency of gene transfer with apically applied JSRV-FIV was markedly less than FIV pseudotyped with VSV-G, even in Ad-HYAL2 complemented epithelia. The inefficient gene transfer with JSRV-FIV in HYAL2 complemented cells suggests that factors other than receptor abundance limit apical gene transfer efficiency with this envelope. JSRV-FIV transduced the distal lung epithelia of rabbits in vivo and transduced primary cultures of rabbit type II cells with 100-fold greater efficiency than primary cultures of rabbit tracheal cells. These data indicate that a lentivirus pseudotyped with the JSRV envelope glycoprotein transduces type II cells with greater efficiency than conducting airway epithelia and provides an example of glycoprotein-mediated cell-specific tropism within a tissue with a widely heterogeneous cell population.
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PMID:Gene transfer to respiratory epithelia with lentivirus pseudotyped with Jaagsiekte sheep retrovirus envelope glycoprotein. 1587 79

Retroviruses express Gag and Pol proteins by translation of unspliced genome-length viral RNA. For some retroviruses, transport of unspliced viral RNA to the cytoplasm is mediated by small regulatory proteins such as human immunodeficiency virus Rev, while other retroviruses contain constitutive transport elements in their RNAs that allow transport without splicing. In this study, we found that the betaretrovirus Jaagsiekte sheep retrovirus (JSRV) encodes within the env gene a trans-acting factor (Rej) necessary for the synthesis of Gag protein from unspliced viral RNA. Deletion of env sequences from a JSRV proviral expression plasmid (pTN3) abolished its ability to produce Gag polyprotein in transfected 293T cells, and Gag synthesis could be restored by cotransfection of an env expression plasmid (DeltaGP). Deletion analysis localized the complementing activity (Rej) to the putative Env signal peptide, and a signal peptide expression construct showed Rej activity. Two other betaretroviruses, mouse mammary tumor virus (MMTV) and human endogenous retrovirus type K, encode analogous factors (Rem and Rec, respectively) that are encoded from doubly spliced env mRNAs. Reverse transcriptase-PCR cloning and sequencing identified alternate internal splicing events in the 5' end of JSRV env that could signify analogous doubly spliced Rej mRNAs, and cDNA clones expressing two of them also showed Rej activity. The predicted Rej proteins contain motifs similar to those found in MMTV Rem and other analogous retroviral regulatory proteins. Interestingly, in most cell lines, JSRV expression plasmids with Rej deleted showed normal transport of unspliced JSRV RNA to the cytoplasm; however, in 293T cells Rej modestly enhanced export of unspliced viral RNA (2.8-fold). Metabolic labeling experiments with [(35)S]methionine indicated that JSRV Rej is required for the synthesis of viral Gag polyprotein. Thus, in most cell lines, the predominant function of Rej is to facilitate translation of unspliced viral mRNA.
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PMID:Jaagsiekte sheep retrovirus encodes a regulatory factor, Rej, required for synthesis of Gag protein. 1977 24

Jaagsiekte sheep retrovirus (JSRV) is a simple betaretrovirus causing a contagious lung cancer of sheep. JSRV encodes unspliced and spliced viral RNAs, among which unspliced RNA encodes Gag and Pol proteins and a singly spliced mRNA encodes Env protein. In another study we found that JSRV encodes a regulatory protein, Rej, that is responsible for synthesis of Gag polyprotein from unspliced viral RNA. Rej is encoded in the 5' end of env, and it enhances nuclear export or accumulation of cytoplasmic unspliced viral RNA in 293T cells but not in most other cell lines (A. Hofacre, T. Nitta, and H. Fan, J. Virol. 83:12483-12498, 2009). In this study, we found that mutations in the 3' end of env in the context of a cytomegalovirus-driven full-length JSRV expression construct abolished Gag protein synthesis and released viruses in 293T cells. These mutants also showed deficits in accumulation of unspliced viral RNA in the cytoplasm. These mutants defined a Rej-responsive element (RejRE). Inhibition of CRM1 but not Tap function prevented nuclear export/accumulation of cytoplasmic unspliced RNA in 293T cells, similarly to other complex retroviruses that express analogous regulator proteins (e.g., human immunodeficiency virus Rev). Structural modeling of the RejRE with Zuker M-fold indicated a region with a predicted stable secondary structure. Mutational analysis in this region indicated the importance of both secondary structures and primary nucleotide sequences in a central stem-bulge-stem structure. In contrast to 293T cells, mutations in the RejRE did not affect the levels of cytoplasmic unspliced RNA in 293 cells, although the unspliced RNA showed partial degradation, perhaps due to lack of translation. RejRE-containing RNA relocalized Rej protein from the nucleus to the cytoplasm in 293 and rat 208F cells, suggesting binding of Rej to the RejRE.
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PMID:Identification and mutational analysis of a Rej response element in Jaagsiekte sheep retrovirus RNA. 1977 34

Diseases caused by animal retroviruses have been recognized since 19th century in veterinary field. Most livestock and companion animals have own retroviruses. To disclose the receptors for these retroviruses will be useful for understanding retroviral pathogenesis, developments of anti-retroviral drugs and vectors for human and animal gene therapies. Of retroviruses in veterinary field, receptors for the following viruses have been identified; equine infectious anemia virus, feline immunodeficiency virus, feline leukemia virus subgroups A, B, C, and T, Jaagsiekte sheep retrovirus, enzootic nasal tumor virus, avian leukosis virus subgroups A, B, C, D, E, and J, reticuloendotheliosis virus, RD-114 virus (a feline endogenous retrovirus), and porcine endogenous retrovirus subgroup A. Primate lentiviruses require two molecules (CD4 and chemokine receptors such as CXCR4) as receptors. Likewise, feline immunodeficiency virus also requires two molecules, i.e., CD134 (an activation marker of CD4 T cells) and CXCR4 in infection. Gammaretroviruses utilize multi-spanning transmembrane proteins, most of which are transporters of amino acids, vitamins and inorganic ions. Betaretroviruses and alpharetroviruses utilize transmembrane and/or GPI-anchored proteins as receptors. In this review, I overviewed receptors for animal retroviruses in veterinary field.
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PMID:[Receptors for animal retroviruses]. 2021 31

Retroviral infections are considered important risk factors for cancer development in humans since approximately 15-20% of cancer worldwide is caused by an infectious agent. This report discusses the most established oncogenic retroviruses, including human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1 and -2), Rous sarcoma virus (RSV), Abelson murine leukemia virus (A-MuLV), Moloney murine leukemia virus (M-MuLV), murine mammary tumor virus (MMTV), bovine leukemia virus, (BLV), Jaagsiekte sheep retrovirus (JSRV), and Friend spleen focus-forming virus (SFFV). The role of retroviruses as inducers of carcinogenesis, the mechanisms underlying oncogenic transformation, and the routes of transmission of several cancer-related retroviral infections are also described. Finally, the impact of cancer-related retroviral infections in the developing world is addressed. This review is an update of carcinogenesis caused by retroviral infections.
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PMID:Tumorigenesis related to retroviral infections. 2211 27