Expression of CXCR4 on feline peripheral blood mononuclear cells: effect of feline immunodeficiency virus infection.

CXCR4 expression on feline peripheral blood mononuclear cells (PBMC) was analyzed. While monocytes and B lymphocytes expressed CXCR4, no CXCR4 was detected on T lymphocytes, in stark contrast to the expression pattern on T lymphocytes from humans. In spite of the important role that CXCR4 plays in infection with feline immunodeficiency virus, expression on PBMC in vivo was unaffected by infection with either a primary or a cell culture-adapted virus strain

Upregulation of surface feline CXCR4 expression following ectopic expression of CCR5: implications for studies of the cell tropism of feline immunodeficiency virus

Feline CXCR4 and CCR5 were expressed in feline cells as fusion proteins with enhanced green fluorescent protein (EGFP). Expression of the EGFP fusion proteins was localized to the cell membrane, and surface expression of CXCR4 was confirmed by using a cross-species-reactive anti-CXCR4 monoclonal antibody. Ectopic expression of feline CCR5 enhanced expression of either endogenous feline CXCR4 or exogenous feline or human CXCR4 expressed from a retrovirus vector, indicating that experiments investigating the effect of CCR5 expression on feline immunodeficiency virus (FIV) infection must be interpreted with caution. Susceptibility to infection with cell culture-adapted strains of FIV or to syncytium formation following transfection with a eukaryotic vector expressing an env gene from a cell culture-adapted strain of virus correlated with expression of either human or feline CXCR4, whereas feline CCR5 had no effect. In contrast, neither CXCR4 nor CCR5 rendered cells permissive to either productive infection with primary strains of FIV or syncytium formation following transfection with primary env gene expression vectors. Screening a panel of Ghost cell lines expressing diverse human chemokine receptors confirmed that CXCR4 alone supported fusion mediated by the FIV Env from cell culture-adapted viruses. CXCR4 expression was upregulated in Ghost cells coexpressing CXCR4 and CCR5 or CXCR4, CCR5, and CCR3, and susceptibility to FIV infection could be correlated with the level of CXCR4 expression. The data suggest that ß-chemokine receptors may influence FIV infection by modulating the expression of CXCR4

Differential utilization of CD134 as a functional receptor by diverse strains of feline immunodeficiency virus

The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, with disease progression, the cell tropism of FIV broadens such that B cells and monocytes/macrophages become significant reservoirs of proviral DNA, suggesting that receptor utilization may alter with disease progression. We examined the receptor utilization of diverse strains of FIV and found that all strains tested utilized CD134 as the primary receptor. Using chimeric feline x human CD134 receptors, the primary determinant of receptor function was mapped to the first cysteine-rich domain (CRD1) of fCD134. For the PPR and B2542 strains, the replacement of CDR1 of fCD134 (amino acids 1 to 64) with human CD134 (hCD134) alone was sufficient to confer nearly optimal receptor function. However, evidence of differential utilization of CD134 was revealed, since strains GL8, CPGammer (CPG41), TM2, 0827, and NCSU1 required determinants in the region spanning amino acids 65 to 85, indicating that these strains may require a more stringent interaction for infection to proceed

Mapping the domains of CD134 as a functional receptor for feline immunodeficiency virus (FIV)

The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, strains of FIV differ in their utilisation of CD134; the prototypic strain PPR, requires a minimal determinant in CRD1 of fCD134 to confer near optimal receptor function while strains such as GL8 require additional determinants in the CD134 CRD2. We map this determinant to a loop in CRD2 governing the interaction between the receptor and its ligand; substitution of amino acids S78N,S79Y,K80E restored full viral receptor activity to the CDR2 of human CD134 in the context of feline CD134 with tyrosine-79 appearing to be the critical residue for restoration of receptor function

Mapping the domains of CD134 as a functional receptor for feline immunodeficiency virus (FIV)

The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, strains of FIV differ in their utilisation of CD134; the prototypic strain PPR, requires a minimal determinant in CRD1 of fCD134 to confer near optimal receptor function while strains such as GL8 require additional determinants in the CD134 CRD2. We map this determinant to a loop in CRD2 governing the interaction between the receptor and its ligand; substitution of amino acids S78N,S79Y,K80E restored full viral receptor activity to the CDR2 of human CD134 in the context of feline CD134 with tyrosine-79 appearing to be the critical residue for restoration of receptor function

Evolution of replication efficiency following infection with a molecularly cloned feline immunodeficiency virus of low virulence

The development of an effective vaccine against human immunodeficiency virus is considered to be the most practicable means of controlling the advancing global AIDS epidemic. Studies with the domestic cat have demonstrated that vaccinal immunity to infection can be induced against feline immunodeficiency virus (FIV); however, protection is largely restricted to laboratory strains of FIV and does not extend to primary strains of the virus. We compared the pathogenicity of two prototypic vaccine challenge strains of FIV derived from molecular clones; the laboratory strain PET<sub>F14</sub> and the primary strain GL8<sub>414</sub>. PET<sub>F14</sub> established a low viral load and had no effect on CD4<sup>+</sup>- or CD8<sup>+</sup>- lymphocyte subsets. In contrast, GL8<sub>414</sub> established a high viral load and induced a significant reduction in the ratio of CD4<sup>+</sup> to CD8<sup>+</sup> lymphocytes by 15 weeks postinfection, suggesting that PET<sub>F14</sub> may be a low-virulence-challenge virus. However, during long-term monitoring of the PET<sub>F14</sub>-infected cats, we observed the emergence of variant viruses in two of three cats. Concomitant with the appearance of the variant viruses, designated 627<sub>W135</sub> and 628<sub>W135</sub>, we observed an expansion of CD8<sup>+</sup>-lymphocyte subpopulations expressing reduced CD8 ß-chain, a phenotype consistent with activation. The variant viruses both carried mutations that reduced the net charge of the V3 loop (K409Q and K409E), giving rise to a reduced ability of the Env proteins to both induce fusion and to establish productive infection in CXCR4-expressing cells. Further, following subsequent challenge of naïve cats with the mutant viruses, the viruses established higher viral loads and induced more marked alterations in CD8<sup>+</sup>-lymphocyte subpopulations than did the parent F14 strain of virus, suggesting that the E409K mutation in the PET<sub>F14</sub> strain contributes to the attenuation of the virus

Use of CD134 as a primary receptor by the feline immunodeficiency virus

Feline immunodeficiency virus (FIV) induces a disease similar to acquired immunodeficiency syndrome (AIDS) in cats, yet in contrast to human immunodeficiency virus (HIV), CD4 is not the viral receptor. We identified a primary receptor for FIV as CD134 (OX40), a T cell activation antigen and costimulatory molecule. CD134 expression promotes viral binding and renders cells permissive for viral entry, productive infection, and syncytium formation. Infection is CXCR4-dependent, analogous to infection with X4 strains of HIV. Thus, despite the evolutionary divergence of the feline and human lentiviruses, both viruses use receptors that target the virus to a subset of cells that are pivotal to the acquired immune response

The effect of temperature on brood duration in three Halicarcinus species (Crustacea :Brachyura: Hymenosomatidae)

The effect of temperature on brood development was investigated for three intertidal hymenosomatid crabs: Halicarcinus cookii, H. varius and H. innominatus in Kaikoura, New Zealand. The duration of brood incubation decreased as temperature increased, as did the interbrood period. The duration of each stage of brood development also decreased with increased temperature, but the proportion of total incubation time for each stage remained relatively similar at different temperatures. Hymenosomatid crabs have determinate growth, but moult to maturity at different sizes, thereafter devoting most of their energy to reproduction. The number of broods a female could carry in her lifetime was estimated for each species. Halicarcinus cookii was estimated to be able to produce eight complete broods of 1146 eggs per lifetime, H. varius was estimated to be able to produce seven complete broods of 1051 eggs per lifetime and H. innominatus was estimated to be able to produce six complete broods of 1081 eggs per life time. With the predicted global temperature rise of 2°C in the next 50 years, the authors estimate that, for all three species, a female could produce one extra brood per lifetime (a 10–15% increase in fecundity depending on species), even more if crabs reach maturity faster, potentially leading to a significant population increas

Vaccination with an Inactivated Virulent Feline Immunodeficiency Virus Engineered to Express High Levels of Env

An inactivated virus vaccine was prepared from a pathogenic isolate of feline immunodeficiency virus containing a mutation that eliminated an endocytic sorting signal in the envelope glycoprotein, increasing its expression on virions. Cats immunized with inactivated preparations of this modified virus exhibited strong titers of antibody to Env by enzyme-linked immunosorbent assay. Evidence of protection following challenge demonstrated the potential of this approach to lentiviral vaccination

Проблема взаємозв’язку громадянського суспільства і державної бюрократії в Україні: деякі сучасні аспекти історіографії дослідження

Розглядається взаємодія громадянського суспільства і державної бюрократії. Зроблено висновок, що позиції українських дослідників відповідають напрацюванням західної наукової традиції стосовно теоретичних, а також практичних способів забезпечення взаємодії інститутів громадянського суспільства і державного апарату.In this article the interrelation between civil society and state bureaucracy is analysed. The conclusion is made that the views of the Ukrainian scientists correlate with the western traditional scientific opinion concerning theoretical and practical ways of ensuring interaction between the civil society institutions and state apparatus