Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early studies with the Gross passage A leukemia virus demonstrated that retroviral infection suppresses cellular and humoral immune responses. In extensive studies of the feline leukemia (FeLV) virus, which can induce profound immunodeficiency disease, are generative anemia and lymphoid, myeloid and erythroid neoplasia, the immunosuppressive effects of this retrovirus could be attributed to the actions of the retroviral envelope protein p15E. We found that a highly conserved, synthetic 17 amino acid peptide synthesized by Cianciolo and co-workers that is homologous to the hydrophilic portion of the otherwise hydrophobic transmembrane envelope protein can suppress polyclonal activation of B-cells, impair production of gamma- and alpha-interferon, inhibit production of interleukin-2, inhibit expression of IL-2 receptors, and suppress responses of cytotoxic lymphocytes. In analyses with inactivated preparations of the human immunodeficiency virus, with Pahwa et al. we demonstrated that purified non-infectious retrovirus and also retroviral proteins, in particular gp120, appeared to produce some of the immunosuppressive properties of HIV, particularly suppression of B-cell activation in response to known B-cell stimulants irrespective of T-cell influence, suppression of T-helper cell functions essential to B-lymphocyte responsiveness, and impaired function of immunoglobulin-secreting cells. Other investigators have also reported strong immunosuppressive or immunostimulatory influences for components of the HIV retrovirus and also gp120 through yet poorly elucidated but certainly complex actions on both T- and B-lymphocyte-mediated immune functions.
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PMID:In vitro immunomodulation and in vivo immunotherapy of retrovirus-induced immunosuppression. 166 53

The transmembrane (TM) envelope protein of lentiviruses, including equine infectious anemia virus (EIAV), is significantly larger than that of other retroviruses and may extend in the C-terminal direction 100 to 200 amino acids beyond the TM domain. This size difference suggests a lentivirus-specific function for the long C-terminal extension. We have investigated the synthesis and processing of the EIAV TM protein by immune precipitation and immunoblotting experiments, by using several envelope-specific peptide antisera. We show that the TM protein in EIAV particles is cleaved by proteolysis to an N-terminal glycosylated 32- to 35-kilodalton (kDa) segment and a C-terminal nonglycosylated 20-kDa segment. The 20-kDa fragment was isolated from virus fractionated by high-pressure liquid chromatography, and its N-terminal amino acid sequence was determined for 13 residues. Together with the known nucleotide sequence, this fixes the cleavage site at a His-Leu bond located 240 amino acids from the N terminus of the TM protein. Since the 32- to 35-kDa fragment and the 20-kDa fragment are not detectable in infected cells, we assume that cleavage occurs in the virus particle and that the viral protease may be responsible. We have also found that some cells producing a tissue-culture-adapted strain of EIAV synthesize a truncated envelope precursor polyprotein. The point of truncation differs slightly in the two cases we have observed but lies just downstream from the membrane-spanning domain, close to the cleavage point described above. In one case, virus producing the truncated envelope protein appeared to be much more infectious than virus producing the full-size protein, suggesting that host cell factors can select for virus on the basis of the C-terminal domain of the TM protein.
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PMID:Synthesis and processing of the transmembrane envelope protein of equine infectious anemia virus. 216 97

Both the polycythemia-inducing and the anemia-inducing strains of Friend spleen focus-forming virus can induce acute erythroleukemia in susceptible adult mice. However, only cells infected with the polycythemia-inducing strain become erythropoietin-independent for proliferation and differentiation. The sequences responsible for the altered erythropoietin responsiveness have previously been localized to a 678-base-pair EcoRI-Cla I fragment at the 3' end of the envelope gene. This region is now further analyzed by dividing it into two fragments by using the Fok I restriction site. Two recombinants were made by replacing either the 558-base-pair EcoRI-Fok I or the 113-base-pair Fok I-Cla I env gene fragments from the anemia-inducing strain of spleen focus-forming virus with sequences derived from the polycythemia-inducing strain. Our results indicate that the 113-base-pair Fok I-Cla I fragment, which encodes primarily the transmembrane domain of the envelope protein, determines erythropoietin-independent growth.
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PMID:Transmembrane domain of the envelope gene of a polycythemia-inducing retrovirus determines erythropoietin-independent growth. 255 98

Bone marrow fibroblast colony-forming units (CFU-F) were evaluated in cats experimentally infected with feline leukemia virus (FeLV). Cats that developed persistent viral infection and anemia (progressor cats) had a progressive decrease in the number of CFU-F at 2, 4, 6, 8, and 10 weeks after inoculation with FeLV. This suppression of CFU-F number in progressor cats ranged from 16 to 44% of the preinoculation CFU-F value. Cats that did not develop persistent viral infection or anemia (regressor cats) had decreased numbers of CFU-F (24% of the preinoculation CFU-F value) at 2 weeks after inoculation, but normal CFU-F numbers at 4, 6, 8, and 10 weeks after inoculation. In vitro incubation of bone marrow mononuclear cells from healthy cats with the 15,000-dalton envelope protein of FeLV resulted in decreased number of CFU-F (21% of that of untreated cultures). The number of CFU-F from bone marrow mononuclear cells incubated with the 27,000-dalton core protein of FeLV was similar to that from untreated cultures.
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PMID:Suppression of feline bone marrow fibroblast colony-forming units by feline leukemia virus. 283 64

We have previously reported that immunization of ponies with a baculovirus-expressed recombinant surface unit envelope protein (rgp90) for equine infectious anemia virus (EIAV) resulted in enhancement of disease symptoms and virus replication in 4 of 4 vaccine recipients subjected to a heterologous virus challenge (rpg90 I vaccine trial) (Wang et al., 1994). To extend these studies of EIAV vaccine enhancement, two additional and independent rgp90 vaccine trials (rgp90 II and rgp90 III) were performed. Combined, a total of 13 ponies were immunized with the rgp90 immunogen using our standard vaccination procedures and challenged with a heterologous strain of EIAV. In contrast to the uniform enhancement observed in the rgp90 I vaccine trial, the severity of clinical symptoms varied markedly among the rgp90 recipients: 5 ponies experienced enhanced disease symptoms, 5 ponies experienced moderate disease symptoms, and 3 ponies remained asymptomatic. Of particular interest, in the 5 ponies with enhanced clinical symptoms was a severe thrombocytopenia (< or = 105,000 platelets/microliter) evident coincident with the first febrile episode following virus challenge. Thrombocytopenia was either absent (7/10 ponies) or substantially delayed (3/10 ponies) in naive control ponies inoculated with the standard EIAVPV challenge. Measurements of virus replication in the challenged vaccine recipients indicated a correlation between the level of viral RNA in plasma and the severity of the disease. Interestingly, an association was not observed between serum antibody reactivity to the vaccine or native viral antigens and the frequency of enhancement. Thus, these observations demonstrate a previously unrecognized complexity of rgp90 vaccine efficacy that has important implications for AIDS vaccine development.
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PMID:Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement. 961 76

The ability of human immunodeficiency virus (HIV)- and equine infectious anaemia virus (EIAV)-based vectors to transduce cell lines from a range of species was compared. Both vectors carried the vesicular stomatitis virus G (VSV-G) envelope protein and encoded an enhanced green fluorescent protein (eGFP) gene driven by a human cytomegalovirus (CMV) early promoter. Immunostaining for viral core proteins and VSV-G was used to demonstrate that the HIV and EIAV vector preparations contained similar numbers of virus particles. Various cell lines were transduced with these vectors and the transduction efficiency was estimated by measuring eGFP expression. Efficient transduction by both vectors was observed in human, hamster, pig, horse, cat and dog cell lines, although EIAV vector was about 10-fold less efficient in human, hamster and pig cells normalised to the total number of viral particles. This could be partly explained by the lower RNA genome levels per particle for EIAV as measured by real-time RT-PCR. Rodent cells appeared to be transduced inefficiently with both vectors, but when the CMV promoter was substituted with the EF1alpha promoter in the HIV vectors, the expression level increased leading to an increase in the measurable level of transduction.
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PMID:Gene transduction efficiency in cells of different species by HIV and EIAV vectors. 1208 41

Infection with human immunodeficiency virus (HIV)-1 can lead to neurological complications that range from mild cognitive and motor impairment to HIV-associated dementia (HAD). The mechanism of brain injury and dementia remains poorly understood. Interestingly, post mortem brain specimen from HAD patients and transgenic mice expressing the viral envelope protein gp120 present with similar neuropathological signs. The cytokine erythropoietin (EPO) is clinically used to treat anemia but has also been found to prevent neuronal death due to inflammation or excitotoxicity. Here we show that EPO protects cerebrocortical neurons against apoptosis induced by HIV-1/gp120.
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PMID:Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage. 1507 10

Friend leukemia virus (FLV) infection strongly enhances gamma-irradiation-induced apoptosis of hematopoietic cells of C3H hosts leading to a lethal anemia. Experiments using p53 knockout mice with the C3H background have clarified that the apoptosis is p53-dependent and would not be associated with changes of cell populations caused by the infection with FLV. In bone marrow cells of FLV + total body irradiation (TBI)-treated C3H mice, the p53 protein was prominently activated to overexpress p21 and bax suggesting that apoptosis-enhancing mechanisms lay upstream of p53 protein in the signaling pathway. Neither of DNA-dependent protein kinase (DNA-PK)-deficient SCID mice nor ataxia telangiectasia mutated (ATM) gene knockout mice with the C3H background exhibited a remarkable enhancement of apoptosis or p53 activation on FLV + TBI-treatment indicating that DNA-PK and ATM were both essential. ATM appeared necessary for introducing DNA damage-induced apoptosis, while DNA-PK enhanced p53-dependent apoptosis under FLV-infection. Surprisingly, viral envelope protein, gp70, was co-precipitated with DNA-PK but not with ATM in FLV + TBI-treated C3H mice. These results indicated that FLV-infection enhances DNA damage-induced apoptosis via p53 activation and that DNA-PK, in association with gp70, might play critical roles in modulating the signaling pathway.
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PMID:DNA-dependent protein kinase enhances DNA damage-induced apoptosis in association with Friend gp70. 1566 Dec 67

The envelope (Env) protein of human immunodeficiency virus type 2 (HIV-2) and the HIV-1 Vpu protein stimulate the release of retroviral particles from human cells that restrict virus production, an activity that we call the enhancement of virus release (EVR). We have previously shown that two separate domains in the HIV-2 envelope protein are required for this activity: a glycine-tyrosine-x-x-hydrophobic (GYxxtheta) motif in the cytoplasmic tail and an unmapped region in the ectodomain of the protein. We here report that the cellular partner of the GYxxtheta motif is the adaptor protein complex AP-2. The mutation of this motif or the depletion of AP-2 by RNA interference abrogated EVR activity and changed the cellular distribution of the Env from a predominantly punctate pattern to a more diffuse distribution. Since the L domain of equine infectious anemia virus (EIAV) contains a Yxxtheta motif that interacts with AP-2, we used both wild-type and L domain-defective particles of HIV-1 and EIAV to examine whether the HIV-2 Env EVR function was analogous to L domain activity. We observed that the production of all particles was stimulated by HIV-2 Env or Vpu, suggesting that the L domain and EVR activities play independent roles in the release of retroviruses. Interestingly, we found that the cytoplasmic tail of the murine leukemia virus (MLV) Env could functionally substitute for the HIV-2 Env tail, but it did so in a manner that did not require a Yxxtheta motif or AP-2. The cellular distribution of the chimeric HIV-2/MLV Env was significantly less punctate than the wild-type Env, although confocal analysis revealed an overlap in the steady-state locations of the two proteins. Taken together, these data suggest that the essential GYxxtheta motif in the HIV-2 Env tail recruits AP-2 in order to direct Env to a cellular pathway or location that is necessary for its ability to enhance virus release but that an alternate mechanism provided by the MLV Env tail can functionally substitute.
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PMID:Recruitment of the adaptor protein 2 complex by the human immunodeficiency virus type 2 envelope protein is necessary for high levels of virus release. 1650 Nov 1

Large-scale production of gene therapeutics comprising equine infectious anaemia virus (EIAV) -based lentiviral vectors (LVs) would benefit from the development of producer cell lines enabling the generation of larger quantities of vector than achievable by transient systems. Such cell lines would contain three vector components (Gag/Pol, VSV-G envelope and genome expression constructs). As the vesicular stomatitis virus (VSV-G) envelope protein is cytotoxic, its expression must be regulated. It is also desirable to regulate Gag/Pol expression to minimise metabolic burden on the cell. The Tet repressor (TetR) system was selected to regulate expression of VSV-G and Gag/Pol, necessitating the introduction of a fourth construct, encoding TetR, into the cell line. We have generated an inducible packaging cell line that shows tight control of the packaging components, and high-titre vector production on transient transfection of the EIAV genome. The cell line is stable for at least 7 weeks in the absence of selective pressure. To verify that this packaging cell line can support the generation of producer cell lines it was transfected stably with an EIAV genome cassette encoding ProSavin; a gene therapeutic for Parkinson's disease. Producer cell lines were generated, which on induction, yielded ProSavin with titres comparable to the transient system.
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PMID:Development of inducible EIAV-based lentiviral vector packaging and producer cell lines. 1926 13


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