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At least 163 records · Page 9Linked to original sources
PubMed1989

Kappa opiate receptor multiplicity: evidence for two U50,488-sensitive kappa 1 subtypes and a novel kappa 3 subtype.

Kappa receptor multiplicity is a complex area. We now present evidence from binding studies suggesting the existence of four kappa receptor subtypes. The guinea pig cerebellum contains high levels of U50,488-sensitive, or kappa 1, receptors. Kappa opiates (U50,488, tifluadom, Mr2034, Mr2266 and Win44,441) compete [3H]ethylketocyclazocine binding to kappa 1 receptors with kappa, values under 10 nM and Hill coefficients of approximately one, as does dynorphin A (kappa 1, 0.27 +/- 0.05 nM; Hill coefficient, 0.83 +/- 0.20, n = 4). However, competition studies with dynorphin B yield a Hill coefficient of 0.46 +/- 0.03 (n = 5) and nonlinear regression analysis of the competition curve is best fit by two sites. alpha-Neoendorphin Neoendorphin competition curves (Hill coefficient, 0.46 +/- 0.07; n = 3) also were best fit with two components. Competition studies with both alpha-neoendorphin and dynorphin B together suggest that both compounds label the same site with high affinity. Similar results were obtained using [3H]U69,593. Dynorphin B and alpha-neoendorphin competed binding with Hill coefficients of 0.45 +/- 0.04 (n = 3) and 0.59 +/- 0.09 (n = 3), respectively. These data suggest two subtypes of kappa 1 receptors in the guinea pig cerebellum: kappa 1a and kappa 1b. Classical kappa opiates and dynorphin A have high affinity for both subtypes whereas dynorphin B and alpha-neoendorphin label kappa 1b over 50-fold more potently than kappa 1a sites. [3H]Naloxone benzoylhydrazone [( 3H]NalBzoH) labels a novel, U50,488-insensitive kappa receptor subtype, kappa 3, in membranes from calf striatum, rat and mouse brain. We now have developed a relatively selective assay in calf striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Mononuclear cell (MNC) subtypes in osteoarthritis synovial fluid. Comparison with MNC subtypes in rheumatoid arthritis synovial fluid.

OBJECTIVE: To examine mononuclear cell (MNC) subtypes in osteoarthritis (OA) synovial fluid (SF) and compare these results with MNC subtypes in SF from patients with rheumatoid arthritis (RA). METHODS: MNC were obtained from SF by gradient centrifugation with Ficoll-Hypaque. MNC subtypes were identified using color immunofluorescence with monoclonal antibody pairs and flow cytometry. RESULTS: Significantly lower percentages of CD3+ (p < 0.01) and CD4+ cells (p < 0.01) were found in patients with OA. No differences were noted between CD8+ cells and the CD4/CD8 ratio. Significantly higher percentages of CD14+ (p < 0.001) and CD16+/CD56+ (p < 0.001) were found in patients with OA. CONCLUSION: Significant differences in MNC subtypes in OA and RA were noted that may reflect differences in pathophysiologic mechanisms operational in each disease.

Aged↗
PubMedDate not supplied

[The isolation and subtyping of the human immunodeficiency virus (HIV) from children in Moldova. The evidence for subtype F].

HIV epidemic related to nosocomial transmission in Romanian nursed children represents up to now more than 50% of paediatric AIDS cases in Europe. Although the sources of this epidemic are obscure, HIV-1 subtype F, a minor form in Brasil and Africa, realised a founder effect in this risk group, thus becoming the major form in Romanian epidemic. This study presents the results of the virus isolation from HIV-infected children in Northeast Romania. Heteroduplex mobility assay (HMA) was performed in order to establish HIV-1 viral subtype for 6 isolates. All tested HIV-1 strains were proved to belong to F subtype. So, our study confirm that HIV-1 subtype F is responsible for the epidemic in the risk group of Romanian nosocomially infected children.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Identification of endothelin receptor subtypes in rat ciliary body using subtype-selective ligands.

The endothelins are important vasoactive ocular peptides and there is some evidence that they may modulate intraocular pressure. We investigated the existence and localization of endothelin receptor subtypes using subtype selective ligands in rat ciliary body. Scatchard transformation of saturation binding experiments revealed that the KD and Bmax for [125I]ET-1 and [125I]ET-3 to membranes from ciliary body were 41.7+/-9 pM and 236+/-20 fmol mg-1 protein and 37. 8+/-0.4 pM and 160+/-2.0 fmol mg-1 protein, respectively. Competitive experiments in the presence of cyclic pentapeptide BQ123 (selective for ETA receptors) and BQ3020 (selective for ETB receptors), demonstrated the existence of ETA and ETB receptors in a ratio of 35:65. Cross-linking of [125I]ET-1 and [125I]ET-3 to ciliary body membranes resulted in the labeling of two bands with apparent molecular masses of 52 and 34 kDa, suggesting that ETA and ETB receptors have similar molecular mass. The 34 Kda band is a proteolytic degradation product of the 52 Kda band. Autoradiographic results show that specific [125I]ET-1 binding sites, displaced by BQ123 and BQ3020, are localized to the ciliary epithelium, supporting the idea that ETA and ETB subtype receptors exist in this tissue.

Animals↗
PubMedDate not supplied

Pharmacological characterizations of recombinant human 5-HT1D alpha and 5-HT1D beta receptor subtypes coupled to adenylate cyclase inhibition in clonal cell lines: apparent differences in drug intrinsic efficacies between human 5-HT1D subtypes.

Recombinant human 5-HT1D alpha and 5-HT1D beta receptor subtypes were stably expressed in NIH-3T3 fibroblasts (1D alpha cell line) and Y-1 adrenocortical tumor cells (1D beta cell line), respectively, for pharmacological evaluations of serotonergic compounds to inhibit forskolin-stimulated cAMP accumulation (FSCA). [3H]LSD saturation studies indicated that 5-HT1D receptor expression levels were slightly higher in the 1D beta cell line (Bmax = 1334 +/- 134 fmol/mg protein) than in the 1D alpha cell line (Bmax = 900 +/- 218 fmol/mg protein). 5-HT inhibited FSCA with similar potencies (EC50 approximately 2 nM) in both assay systems. The rank order of agonist potencies in both clonal cell lines matched their pharmacological profiles previously determined in binding studies: dihydroergotamine > or = 5-carboxamidotryptamine (5-CT) > LSD > or = 5-HT > sumatriptan > 1-naphthylpiperazine (1-NP) > yohimbine > 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT) > 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), with Ki/EC50 ratios greater than unity. Methiothepin acted as a silent antagonist at both human 5-HT1D alpha and 5-HT1D beta receptors with apparent dissociation constants (Kb values) of 12 +/- 1 nM and 3 +/- 1 nM, respectively. Whereas GR 127,935, metergoline, DOI, and quipazine acted as full agonists in the 1D alpha cell line, these compounds behaved as partial agonists in the 1D beta cell line. To determine whether high levels of receptor reserve might mask partial agonist activity in the two second messenger assay systems, studies were performed using the irreversible receptor alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The relationships between receptor occupancy and inhibition of FSCA were determined for 5-HT, sumatriptan, and 1-NP in both clonal cell lines after partial receptor inactivation using Furchgott analysis. Hyperbolic relationships between receptor occupancy and second messenger response were determined for 5-HT in both transfected cell lines. Steep hyperbolic relationships were also found for sumatriptan and 1-NP in the 1D beta cell line whereas nearly linear relationships were observed for these two compounds in the 1D alpha cell line. Moreover, KA/EC50 ratios of these compounds were significantly larger in the 1D beta (10-32) as compared to the 1D alpha (0.9-2.5) cell line. These data are consistent with the hypothesis that the two heterologous expression systems contain a differential amount of receptor reserve. Despite the presence of an apparently larger-receptor reserve in the 1D beta cell line, GR 127,935, metergoline, DOI, and quipazine behaved as partial agonists. Although the potencies (EC50 values) of compounds matched their respective affinity constants (Ki values) for the closely-related 5-HT1D subtypes, differences in intrinsic activities were observed for a few compounds between the two 5-HT1D receptor expression systems. Since receptor reserve is dependent on the properties of both the assay system and drug, the observed variations in intrinsic activity, although influenced by the variable amounts of receptor reserve in the two transfected cell lines, reflect primarily system-independent differences in the intrinsic efficacy of the tested compounds at the two human 5-HT1D receptors. Higher intrinsic efficacies of compounds at the human 5-HT1D alpha receptor relative to the human 5-HT1D beta subtype may be responsible for the higher intrinsic activities observed in the 1D alpha cell line, even though receptor reserve is apparently lower in this system.

Adenylyl Cyclase Inhibitors↗
PubMed2006

Coreceptor switching in HIV-1 subtype B and subtype C.

We use a mathematical model to determine the factors affecting the delayed or rare coreceptor switch in HIV-1 subtype C infected individuals. The model takes into account the two main target cells for the CXCR4-tropic and CCR5-tropic virus and includes the the lytic and non-lytic immune responses. Computer-based simulations and a sensitivity analysis of the model predict that a persistent immune response suppresses the CXCR4-tropic virus to low levels and hence preventing a phenotypic switch. However, not only should the immune response be persistent, but it should have an efficient lytic immune response rather that an efficient non-lytic response. In addition, we also find that the availability of macrophage cells and enhanced viral kinetics are also crucial for the dominance of the R5 strain. We suggest that an altered host environment probably as a result of immune activation may explain the difference in coreceptor switching kinetics between HIV-1 subtype B and subtype C individuals.

HIV Infections↗
PubMed1995

Identification of endothelin receptor subtypes in rat retina using subtype-selective ligands.

We investigate the existence of endothelin receptor subtypes using subtype selective ligands and the presence of immunoreactive (IR) endothelin (ET)-3 (IR-ET-3) by radioimmunoassay (RIA) in rat retina. Scatchard transformation of saturation binding experiments with [125I]ET-3 revealed specific binding sites with a Kd and Bmax values of 42 +/- 12 pM and 111 +/- 24 fmol/mg of protein, respectively. The Kd was similar to that obtain in previous studies using [125I]ET-1. However, the Bmax was 65% of that obtained with [125I]ET-1. Competitive experiments in the presence of the cyclic pentapeptide BQ123 (selective for ETA receptor) and Sarafotoxin 6C (selective for ETB receptor), demonstrated the existence of ETA and ETB receptors in a ratio of 35:65. The order of potency of ET family peptides was ET-3 = ET-1 > S6C for ETB receptor and ET-1 > ET-3 > BQ123 for ETA receptor. Cross-linking of [125I]ET-1 to retinal membranes with disuccinimidyl suberate and SDS-PAGE followed by autoradiography resulted in the labeling of two bands with apparent molecular masses of 52 and 34 kDa. Similar results were obtained using [125I]ET-3, suggesting that ETA and ETB receptors have similar molecular mass. The 34 kDa band is a proteolytic degradation product of the 52 kDa band. The concentration of IR-ET-3 was 1212 +/- 153 fmol/g wet weight in rat retina. All these data suggest that ETs may play a role in neurotransmission or neuromodulation in the retina, operating on both ETA and ETB receptor subtypes present in this tissue.

Animals↗
PubMed1987

H1 histone subtypes and subtype synthesis switches of normal and delobed embryos of Ilyanassa obsoleta.

Histone H1 subtype complexity and H1 histone subtype synthesis switches were characterized during the development of normal embryos of the mud snail Ilyanassa obsoleta. The effect of the removal of the third polar lobe on the normal H1 pattern of synthesis was then investigated in the delobed embryo to determine if classical polar lobe effects are accompanied by a perturbation of these patterns. SDS-gel electrophoresis and fluorography of radiolabeled 5% perchloric acid-soluble nuclear extracts resolved six H1 proteins designated bands 1-6. Bands 1-5 migrate as a cluster of individual bands with similar mobilities. Band 6 has a substantially slower mobility. The synthesis of band 6 is predominant during the first 6 hr post-trefoil. During cleavage and gastrulation bands 1 and 2 are predominant while band 3, 4, and 5 become predominant during organogenesis. In addition, it has been found that removal of the polar lobe delays the off-switch of the early bands 6, 1, and 2 and the on-switch of the late bands 3, 4, and 5. This must result in a different H1 composition in the chromatin of the two embryo types. Cell number data of normal and delobed embryos reveal that the delay in subtype synthesis switching is not caused by an overall delay of cell division in the delobed embryo. However, the data indicate that a subpopulation of cells may not divide, or may divide late, in the delayed embryo. The data also suggest that the D cell lineage may be involved in the control of histone synthesis switching in the A, B, and C cell lineages.

Age Factors↗
PubMed1996

Exclusive expression of the Gs-linked prostaglandin E2 receptor subtype 4 mRNA in mononuclear Jurkat and KM-3 cells and coexpression of subtype 4 and 2 mRNA in U-937 cells.

Prostaglandin E2 (PGE2) is regarded as a potent regulator of the immune system. It can regulate apoptosis in mononuclear cells and modulate the cytokine secretion pattern from T-helper cell subpopulations via an increase in cyclic AMP (cAMP). Of the 4 PGE2 receptor subtypes (EP1-EP4) that are defined pharmacologically by their affinity to subtype-specific ligands and their coupling to G proteins, EP2 and EP4 receptors couple to Gs. It is as yet unknown which of these two receptor subtypes mediates the immunomodulatory effects. By quantitative RT-PCR, the mRNA for EP4 receptors was demonstrated and quantified in the human mononuclear cell lines Jurkat, KM-3 and U-937. However, EP2 receptor mRNA was only present in U-937 cells and was 100-fold less abundant than EP4 receptor mRNA. PGE2 increased cAMP formation with an ED50 of 50-100 nM in all cell lines. cAMP formation was inhibited by the EP4R-specific antagonist AH23848. Since AH23848 inhibited PGE2-induced cAMP formation in U-937 cells to a similar extent as in Jurkat and KM-3, EP2 receptors seem to play, if any, only a secondary role for the PGE2-mediated cAMP formation in U-937 cells.

Biphenyl Compounds↗
PubMed1994

Subtypes of negative symptoms: the primary subtype in schizophrenic and non-schizophrenic patients.

1. The specificity of negative symptoms remains an open question and requires further research. 2. Subtyping negative symptoms has been showed to be a very relevant point for the identification of primary negative symptoms and for their pharmacotherapy. Negative symptoms as a whole have been demonstrated in schizophrenic and non-schizophrenic patients, but these studies did not report about the primary and secondary subtypes. 3. The present study is the first one investigating primary negative symptoms in schizophrenic and non-schizophrenic patients. 84 consecutively admitted psychiatric patients have been studied 5 years after their discharge. 4. All negative symptoms (including the primary subtype) according to Carpenter (Kirkpatrick et al. 1989) and Andreasen (Andreasen 1981) could be identified in all diagnostic groups.

Female↗
PubMed1997

Cloning and stable expression of the mGluR1b subtype of human metabotropic receptors and pharmacological comparison with the mGluR5a subtype.

We isolated and characterized a cDNA encoding the human metabotropic glutamate receptor subtype 1b (hmGluR1b). In situ hybridization studies in human brain regions revealed a higher distribution of mGluR1 mRNA in the dentate gyrus of the hippocampus, the substantia nigra pars compacta and the Purkinje cell layer of the cerebellum compared to other regions studied. We established stable expression of recombinant hmGluR1b in L(tk-) mouse fibroblast and Chinese hamster ovary (CHO-dhfr-) cells. In both expression systems, agonist activation of hmGluR1b stimulated inositol phosphate (InsP) formation and elevation of the cytosolic free calcium ([Ca2+]i), and both responses were blocked by (S)-MCPG. The rank order of potency for agonists was quisqualate > glutamate > (1S,3R)-ACPD in both expression systems. Comparison of the agonist profiles of hmGluR1b and hmGluR5a, both stably expressed in L(tk-) cells, indicated the same rank order of potency (quisqualate > glutamate > or = (RS)-3,5-DHPG > or = (1S,3R)-ACPD), but each of the four agonists were more potent on hmGluR5a than on hmGluR1b. In antagonist studies, (S)-MCPG inhibited the agonist-induced InsP formation and elevation of [Ca2+]i in both hmGluR1b- and hmGluR5a-expressing cells. (S)-4CPG and (S)-4C3HPG both inhibited agonist responses only in hmGluR1b-expressing cells. However, in hmGluR5a-expressing cells the antagonist activity of (S)-4CPG and (S)-4C3HPG was dependent on the agonist used in the study, since they inhibited responses to glutamate but not to quisqualate. Stable cell lines expressing specific subtypes of human mGluRs represent valuable tools for the study of the mechanism of action of mGluRs at the molecular and cellular level and as screening targets for identification of subtype-selective agonists or antagonists.

Animals↗
PubMed1994

Subtyping of Mycobacterium avium complex (MAC) isolates by thin-layer chromatography--distribution of subtypes from patients with AIDS compared with clinically non-significant isolates.

Thin-layer chromatography (TLC) was compared with seroagglutination for subtyping of Mycobacterium avium complex (MAC) bacteria. Seventy-five significant MAC isolates from patients with AIDS were typed by both methods and 36 isolates, judged to be clinically non-significant, were examined by TLC only. Overall, 75% of isolates tested were typable by seroagglutination and 91% by TLC; the results correlated between the two except for minor discrepancies. Serovars 1, 8 and 21 and mixed serovars 1-21 and 1-8-21 were common among isolates from AIDS patients and together represented 83% of isolates compared with only 36% in the non-significant group (odds ratio 8.4; 95% confidence interval 3.4-23.3). This difference remained significant after exclusion of serovar 41 (M. scrofulaceum), which was the commonest isolate (28%) in the non-significant group but was not isolated from patients with AIDS. TLC is useful to supplement seroagglutination for subtyping of MAC. Further study is required to determine whether apparent differences between isolates from patients with AIDS and from other sources reflect differences in virulence or in environmental prevalence of MAC subtypes.

Acquired Immunodeficiency Syndrome↗
PubMed2005

8-NH2-boldine, an antagonist of alpha1A and alpha1B adrenoceptors without affinity for the alpha1D subtype: structural requirements for aporphines at alpha1-adrenoceptor subtypes.

Structure-activity analysis of 21 aporphine derivatives was performed by examining their affinities for cloned human alpha (1A), alpha (1B) and alpha (1D) adrenoceptors (AR) using membranes prepared from rat-1 fibroblasts stably expressing each alpha (1)-AR subtype. All the compounds tested competed for [ (125)I]-HEAT binding with steep and monophasic curves. The most interesting compound was 8-NH (2)-boldine, which retains the selective affinity for alpha(1A)-AR (pKi = 6.37 +/- 0.21) vs. alpha(1B)-AR (pKi = 5.53 +/- 0.11) exhibited by 1,2,9,10-tetraoxygenated aporphines, but shows low affinity for alpha(1D)-AR (pKi < 2.5). Binding studies on native adrenoceptors present in rat cerebral cortex confirms the results obtained for human cloned alpha (1)-AR subtypes. The compounds selective for the alpha (1A) subtype discriminate two binding sites in rat cerebral cortex confirming a mixed population of alpha (1A)- and alpha (1B)-AR in this tissue. All compounds are more selective as inhibitors of [ (3)H]-prazosin binding than of [ (3)H]-diltiazem binding to rat cerebral cortical membranes. A close relationship was found between affinities obtained for cloned alpha (1A)-AR and inhibitory potencies on noradrenaline-induced contraction or inositol phosphate accumulation in tail artery, confirming that there is a homogeneous functional population of alpha(1A)-AR in this vessel. On the contrary, a poor correlation seems to exist between the affinity of 8-NH (2)-boldine for cloned alpha (1D)-AR and its potency as an inhibitor of noradrenaline-induced contraction or inositol phosphate accumulation in rat aorta, which confirms that a heterogeneous population of alpha (1)-AR mediates the adrenergic response in this vessel.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2006

Women infected with HIV type 1 Brazilian variant, subtype B (B'-GWGR motif) have slower progression to AIDS, compared with patients infected with subtype B (B-GPGR motif).

INTRODUCTION: The Brazilian variant of human immunodeficiency virus (HIV) type 1 (HIV-1) subtype B (serotype B'-GWGR) has a tryptophan replacing a proline in position 328 of the HIV-1 envelope, a feature that may induce a different HIV disease progression. We aimed to evaluate the role of the B subtypes of HIV-1 (serotypes B-GPGR and B'-GWGR) on HIV disease progression. METHODS: A total of 137 HIV-infected individuals who had been admitted to the hospital were tested with an anti-V3 serologic assay, using peptides representing 2 HIV-1 subtype B strains, MN and SF2, and 2 Brazilian variant B'-GWGR strains, BR1 and BR2. RESULTS: Of 137 serum samples tested with the anti-V3 serologic assay, 4 (3%) yielded indeterminate results, 74 (54%; from 25 women and 49 men) were found to be B-GPGR, and 59 (43%; from 20 women and 39 men) were found to be the B'-GWGR variant. In general, a longer interval from the first known positive HIV test result to an AIDS-defining event was observed in the B'-GWGR group than in the B-GPGR group (21 vs. 7 months). The CD4+ T cell counts were higher in the B'-GWGR group (median CD4+ T cell count, 65 vs. 31 cells/mm3; P=.01), and women infected with the B'-GWGR variant were less likely to die than were men infected with the same variant (P=.01). The median viral load in the B'-GWGR group was 3.395 copies/mL, compared with 39.350 copies/mL in the B-GPGR group (P=.01). CONCLUSIONS: Taken together, our results indicate that B'-GWGR-infected women may have more-favorable outcomes than B-GPGR-infected subjects.

Adult↗
PubMed2003

Different localization of dendritic cell reservoirs in human immunodeficiency virus-1 subtype B versus subtype E-infected lymph nodes.

The presence of p24 protein was studied in lymph nodes from human immunodeficiency virus (HIV)-positive patients affected by persistent generalized lymphadenopathy. Paraffin-embedded lymph node sections from 50 HIV-1 subtype E-infected lymph nodes from patients in Thailand and 25 HIV-1 presumably subtype B-infected lymph nodes from patients in the United States were immunostained with p24 HIV major core and capsid monoclonal antibodies using the streptavidin-biotin immunoperoxidase technique. Positivity for HIV p24 protein was detected in 20 of 22 HIV-1 subtype B infected nodes in which lymphoid follicles were present, with p24 staining demonstrating a reticular pattern within the germinal centers. Interestingly, no case from 50 clade E-infected lymph nodes containing lymphoid follicles had such a reticular pattern in the germinal centers. This difference could be explained by differential infection of subsets of dendritic cells by the two HIV-1 clades, or perhaps by different routes of initial HIV-1 transmission.

Biopsy↗
PubMed1995

Nucleotide sequence of feline immunodeficiency virus: classification of Japanese isolates into two subtypes which are distinct from non-Japanese subtypes.

Seven isolates of feline immunodeficiency virus (FIV), Shizuoka, Yokohama, Sendai-1, Sendai-2, Fukuoka, Aomori-1, and Aomori-2, were isolated from FIV-seropositive domestic cats in Japan, and their proviral DNAs were amplified by PCR. The nucleotide sequences of their env and gag genes were determined and compared with those of previously described isolates: U.S. and European isolates and one Japanese isolate, TM2. Phylogenetic analyses of complete env gene sequences demonstrate that worldwide isolates are classified into three subtypes: Japanese TM2, Japanese Shizuoka, and non-Japanese subtypes (U.S. and European isolates), with 20% amino acid distances from each other. This pattern indicates that an evolutionary radiation of these three subtypes of FIV occurred at approximately the same time. The sequence data of gag genes also confirmed these results. Furthermore, the Sendai-1 isolate was identified as an imported FIV isolate.

Amino Acid Sequence↗
PubMed1999

Genetic and phenotypic changes accompanying the emergence of epizootic subtype IC Venezuelan equine encephalitis viruses from an enzootic subtype ID progenitor.

Recent studies have indicated that epizootic Venezuelan equine encephalitis (VEE) viruses can evolve from enzootic, subtype ID strains that circulate continuously in lowland tropical forests (A. M. Powers, M. S. Oberste, A. C. Brault, R. Rico-Hesse, S. M. Schmura, J. F. Smith, W. Kang, W. P. Sweeney, and S. C. Weaver, J. Virol. 71:6697-6705, 1997). To identify mutations associated with the phenotypic changes leading to epizootics, we sequenced the entire genomes of two subtype IC epizootic VEE virus strains isolated during a 1992-1993 Venezuelan outbreak and four sympatric, subtype ID enzootic strains closely related to the predicted epizootic progenitor. Analysis by maximum-parsimony phylogenetic methods revealed 25 nucleotide differences which were predicted to have accompanied the 1992 epizootic emergence; 7 of these encoded amino acid changes in the nsP1, nsP3, capsid, and E2 envelope glycoprotein, and 2 were mutations in the 3' untranslated genome region. Comparisons with the genomic sequences of IAB and other IC epizootic VEE virus strains revealed that only one of the seven amino acid changes associated with the 1992 emergence, a threonine-to-methionine change at position 360 of the nsP3 protein, accompanied another VEE virus emergence event. Two changes in the E2 envelope glycoprotein region believed to include the major antigenic determinants, both involving replacement of uncharged residues with arginine, are also candidates for epizootic determinants.

Amino Acid Sequence↗
PubMed2001

Human immunodeficiency virus type 1 (HIV-1) non-B subtypes are similar to HIV-1 subtype B in that coreceptor specificity is a determinant of cytopathicity in human lymphoid tissue infected ex vivo.

We sought to determine the relationship between virus-mediated CD4(+) T-lymphocyte cytopathicity and viral coreceptor preference among various human immunodeficiency virus type 1 (HIV-1) subtypes in an ex vivo-infected human lymphoid tissue model. Our data show that all R5 HIV-1 infections resulted in mild depletion of CD4(+) T lymphocytes, whereas all X4 HIV-1 infections caused severe depletion of CD4(+) T lymphocytes regardless of their subtype origin. Thus, at least for the viruses within subtypes A, B, C, and E that were tested, coreceptor specificity is a critical factor that determines the ability of HIV-1 to deplete CD4(+) T cells in human lymphoid tissue infected ex vivo.

Acquired Immunodeficiency Syndrome↗