Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response of goats infected with caprine arthritis encephalitis virus was evaluated by estimating the binding antibodies in serum. The immunoreactive proteins of the CAEV, strain 63, were determined by immunobloting the lysate against the serum of the infected goat. The major proteins identified were of the molecular weights of 135, 120, 56, 44, 38, 28, 20 and 13 kDa. Proteins with less prominence were of the molecular weights of 96, 32 and 30 kDa. The responses to the viral proteins at several stages of the infection were examined. Antibodies to viral proteins of 135, 121 and 90 kDa were the first to appear in the goat kids that were apparently infected through breast-feeding by infected dam. The time of appearance of these antibodies in the serum varied widely between the goats from one to six months, and preceded the appearence of antibodies to other proteins by two to four weeks. Salient variations revealed in the immunoblot patterns reflect the differences in the immunological responses by the goats to the viral proteins. Littermate goat kids infected through the same dam showed slightly different responses. In the same manner, dissimilarities were observed in the patterns produced by the serums of the damand the corresponding offsprings, when run against the same virus lysate. This study indicates that some differences occur in the immunoblot pattern when this assay is used for diagnosis, although such discrepancies should not affect the interpretation of the diagnostic assay. The host differences in the response to the viral proteins also suggest the potential problems that can be encountered developing an effective vaccine for CAEV, if the binding antibody production reflects that of the neutralizing antibodies in the goats. For effective vaccine coverage, there should be little variability in the immunogenicity of candidate vaccine antigens among the hosts.
Cell Mol Biol (Noisy-le-grand) 2002
PMID:Host differences in serum antibody response during infection of goats by caprine arthritis-encephalitis virus. 1264 48

A method was elaborated to construct combined artificial immunogens mimicking virus particles. The gist was exposing protein antigenic determinants of one virus on the particle surface and delivering plasmids with genes for antigenic proteins of another virus to specialized immune cells. Such immunogens were constructed and shown to induce biosynthesis of specific antibodies against HIV-1 and the tick-borne encephalitis virus. The level and duration of the humoral and cell responses were assayed.
Mol Biol (Mosk)
PMID:[Experimental molecular design of recombinant vaccines]. 1281 63

Members of the California serogroup of bunyaviruses (family Bunyaviridae) are the leading cause of pediatric viral encephalitis in North America. Significant cell death is observed as part of the infection pathology. We now report that a Bunyaviral nonstructural protein termed NSs shows sequence similarity to Reaper, a proapoptotic protein from Drosophila. Although NSs proteins lack the Reaper N-terminal motif critical for IAP inhibition, they do retain other functions of Reaper that map to conserved C-terminal regions. Like Reaper, NSs proteins induce mitochondrial cytochrome c release and caspase activation in cell-free extracts and promote neuronal apoptosis and mortality in a mouse model. Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. We have found that the shared capacity to inhibit translation and induce apoptosis resides in common sequence motifs present in both Reaper and NSs proteins. Data presented here suggest that NSs induce apoptosis through a mechanism similar to that used by Reaper, as both proteins bind to an apoptotic regulator called Scythe and can relieve Scythe inhibition of Hsp70. Thus, bunyavirus NSs proteins have multiple Reaper-like functions that likely contribute to viral pathogenesis by promoting cell death and/or inhibiting cellular translation.
Mol Biol Cell 2003 Oct
PMID:Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper. 1451 26

Human herpesvirus 6 (HHV-6) is a T-lymphotropic herpesvirus, which infects almost all children by the age of two years and persists lifelong. Two distinct variants of HHV-6, HHV-6A and HHV-6B, have been described, and the latter has been shown to be a common cause of acute febrile illnesses in young children, including exanthem subitum (roseola). HHV-6 has also been associated with a number of neurological disorders, including encephalitis and seizures, and the virus has been postulated to play a role in acquired immunodeficiency syndrome (AIDS), multiple sclerosis (MS) and chronic fatigue immunodeficiency syndrome (CFIDS). This review provides a critical summary of research conducted on HHV-6.
Expert Rev Mol Med 1997 Nov 05
PMID:Human herpesvirus 6. 1458 28

We examined sera from goats that developed more rapid and severe clinical disease after vaccination with inactivated caprine arthritis encephalitis virus (CAEV) and virus challenge for CAEV infection-enhancing antibodies. Sera from one control and two vaccinated goats were examined for neutralization or enhancement of virus infection in caprine macrophages. Macrophage cultures were incubated with virus-serum mixtures, then washed and fed with fresh media and incubated. Culture fluid was collected at days 2,4 and 8 post-infection and assayed for reverse transcriptase (RT) activity. Serum from one of the vaccinated goats neutralized virus at 10(-2) and 10(-3) dilutions (p = 0.045 and p = 0.020, respectively). The neutralizing effect was lost at higher dilutions (10(-4) and 10(-5)) of the serum, but no enhancement of infection was seen. Serum from the other vaccinated goat did not show any significant neutralizing effect at either 10(-2) or 10(-3) dilutions and increased infection (40% or greater) at higher dilutions, but the increases were not statistically significant. Therefore, there was no evidence of virus infection-enhancing activity in these sera that would suggest that the severe disease experienced by the vaccinated animals was due to serum enhancement of infection. Alternately, the severe arthritis observed could have resulted from the pro-inflammatory activities of cytokines and chemokines produced by macrophages upon phagocytosis, or receptor-mediated uptake of CAEV-antibody complexes.
Cell Mol Biol (Noisy-le-grand) 2003 Nov
PMID:Lack of enhancement of caprine arthritis encephalitis virus infection in monocyte-derived macrophage cultures by sera from goats that developed severe arthritis after vaccination and virus challenge. 1468 1

Human African trypanosomiasis (HAT, sleeping sickness) is a devastating disease caused by infection with Trypanosoma brucei ssp. These hemoflagellates invade the central nervous system (CNS) and induce meningo-encephalitis, neuronal demyelination, blood-brain-barrier (BBB) dysfunction, peri-vascular infiltration, astrocytosis and apoptosis. The molecular basis of these manifestations is unclear. We previously reported T. brucei-induced apoptosis in cerebella and brain-stem nuclei in mice at peak parasitemia. Here, we identify and characterize a trypanosome apoptotic factor (TAF) expressed by T. brucei that mediates apoptosis in mouse-brain and human-brain vascular endothelial cells (HBVEC). Molecular, biochemical and apoptotic assays, coupled with surface enhanced laser desorption ionization (SELDI), and protein database analyses were utilized to show that TAF is a soluble, non-serum, parasite-derived, heat-labile protein that causes DNA laddering and apoptosis in HBVEC. Protein-chip assay analysis of the SELDI spectrum of infected mouse serum and procyclic culture supernatants revealed a single major peak at 8652.7 Da. Further database analysis indicated that the TAF may be a procyclin or procyclin derivative. A synthetic 27 mer peptide (ProEP2-1), corresponding to a region common to EP procyclins (EP2-1), induced apoptosis in HBVEC and in cerebella of mice similar to that induced in T. brucei-infected mice. Western blot analysis utilizing an anti-procyclin monoclonal antibody (mAb) revealed that TAF is present in infected but not uninfected brain tissue lysates. Furthermore, this mAb blocked T. brucei- and ProEP2-1-induced apoptosis in HBVEC in vitro. We conclude that T. brucei TAF or its derivative(s) play a major role in the apoptosis associated with HAT pathology.
Mol Biochem Parasitol 2004 Feb
PMID:Trypanosome apoptotic factor mediates apoptosis in human brain vascular endothelial cells. 1469 35

Glatiramer acetate (GA; Copaxone, also known as Copolymer 1 or Cop-1), a copolymer of amino acids, is very effective in the suppression of experimental autoimmune encephalitis (EAE), the animal model for multiple sclerosis (MS), in various species including primates. The immunological cross-reaction between the myelin basic protein and GA serves as the basis for the suppressive activity of GA in EAE, by the induction of antigen-specific suppressor cells. The mode of action of GA is by initial strong promiscuous binding to major histocompatibility complex class II molecules and competition with MBP and other myelin proteins for such binding and presentation to T cells. Suppressor T cells induced by GA are of the Th2 type, migrate to the brain and lead to in situ bystander suppression. Clinical trials with GA, both phase II and phase III, were performed in relapsing-remitting MS (RRMS) patients, and demonstrated efficacy in reducing the relapse rate, decreasing MRI-assessed disease activity and burden and slowing progression of disability. GA is generally well tolerated and is not associated with influenza-like symptoms and formation of neutralizing antibodies seen with beta-interferons. It exerts its suppressive effect primarily by immunomodulation, and has recently shown ameliorating effect in a few additional autoimmune disorders as well as in graft rejection. At present GA is considered a valuable first-line treatment option for patients with RRMS.
J Mol Recognit
PMID:Immunomodulation by the copolymer glatiramer acetate. 1473 33

Several unusual features were observed during routine histopathological confirmation of a clinical diagnosis of Alzheimer's disease (AD) in an 85-year-old, right-handed, married male. The patient presented with a 12-year history of slowly progressive cognitive impairment, which increased in severity just prior to death. Detailed postmortem examination of the frontal lobes revealed a significant number of neuritic plaques and neurofibrillary tangles. Multifocal spongiform encephalopathic changes, mononuclear perivascular infiltrates, subcortical demyelination and gliosis were also found. Of particular interest were well-defined neuronal and astrocytic intranuclear inclusion bodies (Cowdry type I and I), suggestive of viral disease. Electron microscopy, immunohistochemical and immunohistofluorescent studies confirmed a Herpes simplex type I encephalitis (HSV-I). These histological results and the clinical history of progression suggest that reactivation of a latent viral infection may have contributed to the rapid progression of dementia prior to death. The present analysis underscores the fact that multiple etiologic factors may act simultaneously to produce dementia. While one such process may be identified or diagnosed (in the present case AD), it is necessary to be open to the possibility that another mechanism may come into play during the time course of that illness. A differential diagnosis may be difficult when the symptoms of the two disease processes are very similar. Such may be the case if there is reactivation of a previously undiagnosed herpes virus infection. With the development of PCR and in situ hybridization diagnosis will be simplified and more definitive.
Cell Mol Biol (Noisy-le-grand) 2003 Dec
PMID:Coexistence of Alzheimer disease neuropathology with herpes simplex encephalitis. 1498 92

The thick-borne encephalitis virus (TBEV), which is widespread in the Eurasian continent, belongs to the Flaviviridae family, Flavirus genus, and comprises the Far Eastern, Siberian and West European subtypes. It was for the first time that the gene part of the E 24 strain envelope glycoprotein of TBEV, which caused infection in residents of the South of Russia's Far East, was analyzed. It was established that the TBEV Far-Eastern subtype causes different-severity disease cases ranging from the focal ones with the lethal outcome to latent infection forms. On the basis of the phylogenetic analysis, the Far-Eastern subtype was shared between 4 sub-clusters, 2 of which constitute a majority of the analyzed TBEV strains.
Mol Gen Mikrobiol Virusol 2004
PMID:[Molecular typing of the tick-borne encephalitis virus isolated from patients with different-infection severities in the south of Russia's Far East]. 1516 19

Sindbis virus infects neurons of the brain and spinal cord leading to neuronal apoptosis and encephalitis in mice. During postnatal development, neurons of mice remain susceptible to infection but become refractory to SV-induced programmed cell death. Failure to undergo programmed cell death results in a persistent infection. However, some neurovirulent strains of Sindbis virus overcome the age-dependent protective function in neurons, leading to enhanced apoptotic cell death in the central nervous system and higher mortality rates. Sindbis virus infections can also cause hind-limb paralysis due to the death of infected spinal cord motor neurons. However, spinal cord neuron death in older mice appears to occur by mechanisms that differ from classical apoptosis observed in newborn mice based on the morphology of dying neurons at these two sites. Sindbis virus infections of mosquitoes and some mosquito cell lines, on the other hand, do not induce cell death but persistent infections, a phenomenon also observed occasionally in cultured mammalian cells as well as in brains of infected mice surviving lethal infections. Thus, both viral and cellular factors contribute to the varied outcomes of infection. The molecular mechanisms that govern the susceptibility or resistance of particular cell types to SV-induced cell death are not well understood. Furthermore, the cellular execution machinery that produces the characteristic morphological distinctions between brain and spinal cord (i.e. apoptotic versus non-apoptotic) remain to be discovered.
Prog Mol Subcell Biol 2004
PMID:Neuronal apoptosis pathways in Sindbis virus encephalitis. 1517 8


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