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

Pastoral production is associated with increased peste des petits ruminants seroprevalence in northern Tanzania across sheep, goats and cattle

Peste des petits ruminants virus (PPRV) causes a contagious disease of high morbidity and mortality in small ruminant populations globally. Using cross-sectional serosurvey data collected in 2016, our study investigated PPRV seroprevalence and risk factors among sheep, goats and cattle in 20 agropastoral (AP) and pastoral (P) villages in northern Tanzania. Overall observed seroprevalence was 21.1% (95% exact confidence interval (CI) 20.1–22.0) with 5.8% seroprevalence among agropastoral (95% CI 5.0–6.7) and 30.7% among pastoral villages (95% CI 29.3–32.0). Seropositivity varied significantly by management (production) system. Our study applied the catalytic framework to estimate the force of infection. The associated reproductive numbers (R0) were estimated at 1.36 (95% CI 1.32–1.39), 1.40 (95% CI 1.37–1.44) and 1.13 (95% CI 1.11–1.14) for sheep, goats and cattle, respectively. For sheep and goats, these R0 values are likely underestimates due to infection-associated mortality. Spatial heterogeneity in risk among pairs of species across 20 villages was significantly positively correlated (R2: 0.59–0.69), suggesting either cross-species transmission or common, external risk factors affecting all species. The non-negligible seroconversion in cattle may represent spillover or cattle-to-cattle transmission and must be investigated further to understand the role of cattle in PPRV transmission ahead of upcoming eradication efforts

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

Variability of humidity conditions in the Arctic during the first International Polar Year, 1882-83

Of all the early instrumental data for the Arctic, the meteorological data gathered during the first International Polar Year, in 1882–83 (IPY-1), are the best in terms of coverage, quality and resolution. Research carried out during IPY-1 scientific expeditions brought a significant contribution to the development of hygrometry in polar regions at the end of the 19th century. The present paper gives a detailed analysis of a unique series of humidity measurements that were carried out during IPY-1 at hourly resolutions at nine meteorological stations, relatively evenly distributed in the High Arctic. It gives an overall view of the humidity conditions prevalent in the Arctic at that time. The results show that the spatial distribution of atmospheric water vapour pressure (e) and relative humidity (RH) in the Arctic during IPY-1 was similar to the present. In the annual course the highest values of e were noted in July and August, while the lowest occurred in the cold half of the year. In comparison to present-day conditions (1961–1990), the mean values of RH in the IPY-1 period (September 1882 to July 1883) were higher by 2.4–5.6%. Most of the changes observed between historical and modern RH values are not significant. The majority of historical daily RH values lie between a distance of less than two standard deviations from current long-term monthly means