Characterization of monoclonal antibodies against the p17 core protein of the human immunodeficiency virus 1

Five mouse hybridomas which produce monoclonal antibodies against the p17 core protein of HIV-1 have been isolated. Cross-competition assays and mapping with synthetic peptides demonstrate that two closely related epitopes are identified by these antibodies. Directed against two neighbouring peptides at the carboxy-terminal end of the molecule, they can be used for the selective detection of p17 polypeptide in a viral extract or in an infected cell lysate by a solid-phase sandwich enzyme immunoassay. © 1990.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Glycine-Amide Is an Active Metabolite of the Antiretroviral Tripeptide Glycyl-Prolyl-Glycine-Amide

The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of human immunodeficiency virus (HIV) type 1 (HIV-1) in vitro, probably by interfering with capsid formation. The aim of the present study was to determine whether the metabolites glycyl-proline (GP-OH), glycine (G-OH), prolyl-glycine-amide (PG-NH(2)), proline (P-OH), and glycine-amide (G-NH(2)) from proteolytic cleavage may inhibit the replication of HIV-1 in vitro. PG-NH(2) has previously been shown to have a modest effect on HIV-1 replication. In the present study we show that G-NH(2) exhibits a pronounced inhibitory effect on HIV-1. This effect was not due to a decrease in cell proliferation or viability and could not be shown for herpes simplex virus type 1. The G-NH(2) concentration that inhibited virus replication by 50% (IC(50)) was equimolar to that of GPG-NH(2) and ranged from 3 to 41 μM. Transmission electron microscopy revealed that the effect of G-NH(2) on HIV-1 morphology was equivalent to that of GPG-NH(2) and showed disarranged capsid structures, indicating interference with capsid formation. Serial passage of HIV-infected cells with G-NH(2) for more than 20 subcultivations did not decrease the susceptibility to the compound. The results from this study suggest that GPG-NH(2) might act as a prodrug and that G-NH(2) is an active antiretroviral metabolite

Activity of the Small Modified Amino Acid α-Hydroxy Glycineamide on In Vitro and In Vivo Human Immunodeficiency Virus Type 1 Capsid Assembly and Infectivity▿

Upon maturation of the human immunodeficiency virus type 1 (HIV-1) virion, proteolytic cleavage of the Gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. Virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. We have reported earlier that glycineamide (G-NH2), when added to the culture medium of infected cells, inhibits HIV-1 replication and that HIV-1 particles with aberrant core structures were formed. Here we show that it is not G-NH2 itself but a metabolite thereof, α-hydroxy-glycineamide (α-HGA), that is responsible for the antiviral activity. We show that α-HGA inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitors but has no effect on the replication of any of 10 different RNA and DNA viruses. α-HGA affected the ability of the HIV-1 capsid protein to assemble into tubular or core structures in vitro and in vivo, probably by binding to the hinge region between the N- and C-terminal domains of the HIV-1 capsid protein as indicated by matrix-assisted laser desorption ionization-mass spectrometry results. As an antiviral compound, α-HGA has an unusually simple structure, a pronounced antiviral specificity, and a novel mechanism of antiviral action. As such, it might prove to be a lead compound for a new class of anti-HIV substances

First Year Dispersion of White-tailed Sea Eagles from Central Europe, Based on GPS/GSM Telemetry

Austria, Czech Republic and Hungary are located in central Europe, where the white-tailed sea eagle Haliaeetus albicilla (WTSEs) was one of the most frequent large raptor species during the 19th century, with substantial numbers of breeding pairs and wintering individuals. Due to landscape changes, direct persecution and intensified agriculture the population decreased dramatically in the 20th century. The species completely disappeared as a breeder from Czech Republic since at least 1920s until 1970s or even 1980s (Bělka, Horal, 2009) as well as from Austria since 1960s until the late 1990s (Probst, Peter, 2009; Probst, 2009). In Hungary, population of this once a widespread breeder (in 19th century) continually decreased until 1970s when a population minimum of ca 20 breeding pairs was reached, most of them in southern Danube valley (Bank et al., 2004). Later on, the breeding population began to recover slowly and now the breeding population consists from 35 territorial pairs (30 breeding) in Austria in 2017 (Probst, Pichler, 2017), 116 known breeding pairs in Czech Republic in 2016 (Bělka, 2017) and 279–307 breeding (egg-laying) pairs in Hungary in 2016 (Szelényi, 2016). It seems that WTSEs from Germany and Poland predominated in recolonization of the population in the western and northern part of the Czech Republic, and that the core Danube population was predominant in the recolonization of southeastern part of the Czech Republic and eastern Austria and Hungary. Moreover, ringing data and recent genetic studies suggest that WTSE populations in central Europe may even have been reestablished by eagles from North European populations (Literák et al., 2007, Nemesházi et al., 2016). Because there are only limited data about a dispersion of WTSEs from this recovered Central European population based on ringing data and because GPS/GSM telemetry is much more powerful tool for spatio-temporal studies than ringing activities, the aim of our study was to reveal the first year dispersion of WTE from central Europe using GPS/GSM telemetry