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

Two crystal forms of recombinant p26 capsid protein (CA) from the equine infectious anemia virus (EIAV) have in common an antiparallel four-helix bundle dimer interface between N-terminal domains (NTDs). The dimer interface provides a lenient scaffold to accommodate the wide sequence variation in these helices within lentivirus CA. Pairs of dimers weakly associate to form exact or approximate D2 symmetry tetramers. In one of the two crystal forms, the tetramers are linked via dimerization of C-terminal domains (CTDs). We propose that the observed NTD and CTD homodimer interactions are involved in the assembly of the lentivirus capsid. The NTD homodimer shape readily suggests a model for the mature capsid core, based on hexagonal packing with dimensions and surface topology resembling described EIAV capsid cores. Combining available data for human immunodeficiency virus and EIAV CA, we also propose an assembly pathway for maturation of the lentivirus capsid core following proteolytic cleavage of the gag polyprotein precursor.
 ...
PMID:Model for lentivirus capsid core assembly based on crystal dimers of EIAV p26. 993 Dec 51

Antigen-specific T-helper (Th) lymphocytes are critical for the development of antiviral humoral responses and the expansion of cytotoxic T lymphocytes (CTL). Identification of relevant Th lymphocyte epitopes remains an important step in the development of an efficacious subunit peptide vaccine against equine infectious anemia virus (EIAV), a naturally occurring lentivirus of horses. This study describes Th lymphocyte reactivity in EIAV carrier horses to two proteins, p26 and p15, encoded by the relatively conserved EIAV gag gene. Using partially overlapping peptides, multideterminant and possibly promiscuous epitopes were identified within p26. One peptide was identified which reacted with peripheral blood mononuclear cells (PBMC) from all five EIAV-infected horses, and three other peptides were identified which reacted with PBMC from four of five EIAV-infected horses. Four additional peptides containing both CTL and Th lymphocyte epitopes were also identified. Multiple epitopes were recognized in a region corresponding to the major homology region of the human immunodeficiency virus, a region with significant sequence similarity to other lentiviruses including simian immunodeficiency virus, puma lentivirus, feline immunodeficiency virus, Jembrana disease virus, visna virus, and caprine arthritis encephalitis virus. PBMC reactivity to p15 peptides from EIAV carrier horses also occurred. Multiple p15 peptides were shown to be reactive, but not all infected horses had Th lymphocytes recognizing p15 epitopes. The identification of peptides reactive with PBMC from outbred horses, some of which encoded both CTL and Th lymphocyte epitopes, should contribute to the design of synthetic peptide or recombinant vector vaccines for EIAV.
 ...
PMID:Gag protein epitopes recognized by CD4(+) T-helper lymphocytes from equine infectious anemia virus-infected carrier horses. 1019 22

We have constructed a non-primate lentiviral vector system based on the equine infectious anaemia virus (EIAV). This system is able to transduce both dividing and non-dividing cells, including primary cultured hippocampal neurons and neurons and glia in the adult rat central nervous system (CNS), at efficiencies comparable with HIV-based vectors. We demonstrate that the only EIAV proteins required for this activity are gag/pol and that the only accessory protein required for vector production is rev. In addition, we show that the pol encoded dUTPase activity that is found in all non-primate lentiviruses is not required. The vectors can be pseudotyped with a range of envelopes including rabies G and MLV 4070A and can be concentrated to high titres. The ability of EIAV to infect mitotically inactive cells makes this vector an attractive alternative to the immunodeficiency viruses for gene therapy.
 ...
PMID:Stable gene transfer to the nervous system using a non-primate lentiviral vector. 1060 76

An attenuated equine infectious anemia virus (EIAV), named V26, was previously obtained after 50 passages of the Japanese virulent strain V70 in primary macrophage culture. To clarify the differences between both viruses, their full-length sequences were determined. There were higher mutations in S2 (6.15% amino acid difference) and LTR (10.7% nucleotide difference). The presumed initiation codon of the S2 gene was absent from the sequence of V26. There was a large insertion within the long-terminal repeat (LTR) U3 hypervariable region of V26. In addition, there were minor mutations in gag (1.22% amino acid difference), pol (1.05% amino acid difference) and env (1. 65% amino acid difference) regions, but no mutation in tat region. No mutations were observed in the principal neutralizing domain in the gp90. Thus, the mutations in the S2 and LTR might be the major target sites of mutation in EIAV during serial passages in vitro.
 ...
PMID:Mutations occurring during serial passage of Japanese equine infectious anemia virus in primary horse macrophages. 1093 Jun 66

Feline leukemia virus (FeLV) subgroup B arises de novo through recombination between the env genes of exogenous FeLV subgroup A and endogenous FeLV-like sequences. FeLV-B, which by itself is poorly infectious, will increase to high titer in the presence of FeLV-A, and is associated with FeLV-related neoplastic disease. Although the participation of FeLV-B in disease progression has not been definitively proven, circumstantial evidence supports the hypothesis that the generation of FeLV-B is linked to disease progression. The present study was designed to evaluate whether increasing the levels of FeLV-B early in FeLV-A infection could result in reduction of the incubation period for development of neoplastic disease. For this study, an isolate of FeLV-B, designated FeLV-1B3, was biologically cloned, partially sequenced, and subgroup typed. In in vivo studies, none of the neonatal cats inoculated with FeLV-1B3 alone converted to viremia positive, and all remained healthy throughout the observation period. All of the kittens inoculated with FeLV-A alone became chronically viremic, and those held for long-term observation all developed either neoplastic disease or anemia. However, kittens inoculated with the combination of FeLV-1B3 and FeLV-A showed attenuated infections whereby the majority of cats failed to develop chronic viremia. The apparent interference of FeLV-A infection by FeLV-B was time and titer dependent. This unexpected result suggests that FeLV-B may act as an attenuated virus, causing inhibition of FeLV-A possibly through an immune-mediated mechanism. Partial support for this view was provided by postmortem examination of cats inoculated with FeLV-1B3 alone. Even though none of these cats became viremic, FeLV antigen was detected as focal infections in select tissues, especially salivary gland epithelium, where enough antigen may be expressed to provide an immunizing dose against gag and pol cross-reacting antigens. This work may also provide another approach to vaccine development based on endogenous retrovirus vector systems.
 ...
PMID:Inhibition of feline leukemia virus subgroup A infection by coinoculation with subgroup B. 1106 34

An 11-mo-old captive-bred male neutered bobcat (Felis rufus) presented with lethargy, anorexia, leukopenia, neutropenia, lymphopenia, and nonregenerative anemia. The animal was diagnosed as feline leukemia virus (FeLV) positive by immunofluorescent antibody and enzyme-linked immunosorbant assay (ELISA) testing. It died despite supportive care. Pathologic examination revealed multifocal non-suppurative encephalitis, diffuse interstitial pneumonia, multifocal hepatocellular necrosis, non-suppurative peritonitis, and lymphoid depletion. FeLV was isolated from peripheral blood mononuclear cells, bone marrow, spleen, and lymph node. FeLV-specific gag sequences were amplified by DNA polymerase chain reaction (PCR) and aligned with known domestic cat FeLV's. The source of the virus was speculated to be a domestic cat that was a surrogate nurse. Case reports of FeLV in nondomestic felids are few, and FeLV does not appear to be enzootic in wild felids, except European wildcats (Felis silvestris) in France and Scotland. Introduction of FeLV into free-living and captive nondomestic felid populations could have serious consequences for their health and survival. Measures to prevent the introduction of this virus to nondomestic felids are warranted.
 ...
PMID:Feline leukemia virus in a captive bobcat. 1127 97

A nested polymerase chain reaction (PCR) amplifying a region of the gag gene of equine infectious anemia virus (EIAV) was developed for the rapid and direct detection of proviral DNA from the peripheral blood of naturally infected horses and was compared with the Coggins test. DNA prepared from white blood cells of 122 field horses from 15 stables with reported cases of EIAV and one seronegative stable were analysed. Amplifications of expected size fragments were obtained by nested PCR for 88 horses using two different sets of primers targeting the gag region. The specificity of the amplified products was confirmed by hybridization using a digoxigenin-labeled probe. Gag-nested PCR-restriction fragment length polymorphism analysis distinguished two different subtypes of gag gene, A and B. Subtype A was found to be the most prevalent among the infected horses that were tested. The PCR-gag amplified sequence of subtype A shared 84.6% nucleotide and 93% deduced amino acid sequence identities with the prototype Wyoming strain whereas subtype B sequence was almost 100% identical to the prototype. Sequence analysis of gag subtype A suggests the presence of a novel EIAV variant among infected horses in Canada. The nested PCR assay developed in the present study detected more EIAV positive animals and was found as specific as the agar gel immunodiffusion (Coggins) assay and offers great potential a diagnostic test for the detection of EIAV infections in field horses.
 ...
PMID:Detection of horses infected naturally with equine infectious anemia virus by nested polymerase chain reaction. 1133 44

Synthesis of Gag-Pol polyproteins of retroviruses requires ribosomes to shift translational reading frame once or twice in a -1 direction to read through the stop codon in the gag reading frame. It is generally believed that a slippery sequence and a downstream RNA structure are required for the programmed -1 ribosomal frameshifting. However, the mechanism regulating the Gag-Pol frameshifting remains poorly understood. In this report, we have defined specific mRNA elements required for sufficient ribosomal frameshifting in equine anemia infectious virus (EIAV) by using full-length provirus replication and Gag/Gag-Pol expression systems. The results of these studies revealed that frameshifting efficiency and viral replication were dependent on a characteristic slippery sequence, a five-base-paired GC stretch, and a pseudoknot structure. Heterologous slippery sequences from human immunodeficiency virus type 1 and visna virus were able to substitute for the EIAV slippery sequence in supporting EIAV replication. Disruption of the GC-paired stretch abolished the frameshifting required for viral replication, and disruption of the pseudoknot reduced the frameshifting efficiency by 60%. Our data indicated that maintenance of the essential RNA signals (slippery sequences and structural elements) in this region of the genomic mRNA was critical for sufficient ribosomal frameshifting and EIAV replication, while concomitant alterations in the amino acids translated from the same region of the mRNA could be tolerated during replication. The data further indicated that proviral mutations that reduced frameshifting efficiency by as much as 50% continued to sustain viral replication and that greater reductions in frameshifting efficiency lead to replication defects. These studies define for the first time the RNA sequence and structural determinants of Gag-Pol frameshifting necessary for EIAV replication, reveal novel aspects relative to frameshifting elements described for other retroviruses, and provide new genetic determinants that can be evaluated as potential antiviral targets.
 ...
PMID:Characterization of RNA elements that regulate gag-pol ribosomal frameshifting in equine infectious anemia virus. 1297 Apr 12

Exogenous type D simian retroviruses (SRV/D) are prevalent in captive and feral populations of various macaque monkeys. Thus far, five subtypes of SRV/Ds have been reported, three of which (SRV-1, -2 and -3) have been molecularly characterized. Two SRV/D strains (N27 and T150) were isolated from seropositive cynomolgus macaques at the Tsukuba Primate Center (TPC) in Japan, showing clinical signs of SRV/D infection, including anemia and persistent unresponsive diarrhea. Electron microscopy demonstrated that both SRV/D isolates have a virion morphology typical of type D retrovirus. The SRV/D N27 and T150 isolates were essentially the same based on sequence analysis. From homology analysis of the entire gag sequence, the N27 isolate is closely related to the other known SRV/Ds but is distinct from the three molecularly characterized SRV/Ds. Thus, we have tentatively designated the N27 and T150 viruses isolated from TPC cynomolgus macaques as SRV/D-Tsukuba (SRV/D-T).
 ...
PMID:Isolation and characterization of a new simian retrovirus type D subtype from monkeys at the Tsukuba Primate Center, Japan. 1571 73

The exogenous simian type D retroviruses (SRV/Ds) are prevalent in macaque monkeys and sometimes cause immunodeficiency with anemia, weight loss, and persistent unresponsive diarrhea. SRV/D isolates are classified as subtypes 1 to 6, and the entire sequences of the gag region of SRV/D-1, -2, and -3 and SRV/D-Tsukuba (SRV/D-T) have been determined. We designed specific primers in the gag region of SRV/D-T that enabled us to directly detect by polymerase chain reaction (PCR) SRV/D-T proviral DNA sequences in DNA extracted from whole blood. Using this assay and another PCR assay that detects multiple SRV/D subtypes, we performed a survey for SRV/D infection in our specific pathogen-free (SPF) and conventional colonies at Tsukuba Primate Center (TPC). In the SPF colony, no SRV/D signal was detected in any animal. On the other hand, SRV/D-T was detected in 11 of 49 animals (22.5%) in the conventional colony. SRV/D-T was the only SRV/D subtype detected. Consequently, SRV/D-T is the major SRV/D subtype present in cynomolgus monkeys at TPC.
 ...
PMID:Survey of captive cynomolgus macaque colonies for SRV/D infection using polymerase chain reaction assays. 1588 76


<< Previous 1 2 3 4 5 6 Next >>