ABSTRACT
A novel synthetic strategy is described which may be used to prepare analogues of the antimalarial, fungal metabolite apicidin. Compared to the natural product, one analogue shows potent and selective activity in vitro against the parasite Trypanosoma brucei and low mammalian cell toxicity.
Subject(s)
Peptides, Cyclic/chemical synthesis , Trypanocidal Agents/chemical synthesis , Animals , Parasitic Sensitivity Tests , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Trypanosoma brucei brucei/drug effectsABSTRACT
Foamy virus (FV) infection has been implicated in the pathogenesis of sporadic motor neuron disease (MND) by means of serological assays. To confirm these results we tested serum and cerebrospinal fluid (CSF) samples from 23 cases of clinically verified non-familial MND and 11 cases of suspected non-familial MND for the presence of FV infection as determined by Western blot (WB) and indirect immunofluorescence assay (IFA). Using the same tests we also screened sera from 87 healthy chimpanzees for the presence of FV antibodies. None of the human samples in question tested positive. However, the testing revealed that 84 of 87 chimpanzees (96.6%) were seropositive for FV, indicating that combined WB and IFA are suitable methods for the serodiagnosis of FV infection. Given these results an association of FV infection and sporadic MND is highly improbable. Furthermore a suggested therapeutic trial with anti-retroviral drugs appears unjustified.
Subject(s)
Amyotrophic Lateral Sclerosis/virology , Antibodies, Viral/blood , Motor Neuron Disease/virology , Retroviridae Infections/complications , Spumavirus/isolation & purification , Adult , Aged , Amyotrophic Lateral Sclerosis/immunology , Animals , Cell Line , Cricetinae , Female , Humans , Male , Middle Aged , Motor Neuron Disease/immunology , Pan troglodytes , Retroviridae Infections/virology , Spumavirus/immunologyABSTRACT
Foamy viruses belong to the retroviruses which possess a complex genome structure. The human foamy virus (HFV) isolate bears three open reading frames (the so-called bel genes) in the 3' region of the genome which have been reported to give rise to possibly six different proteins via alternative splicing (W. Muranyi and R. M. Flügel, J. Virol. 65:727-735, 1991). In order to analyze the requirements of these proteins for HFV replication in vitro, we constructed a set of single and combinatory bel gene mutants of an infectious molecular clone of HFV. The mutant which lacked the transacting activator, bel-1, was found to be replication incompetent. All other mutants replicated equally well and gave rise to comparable titers of infectious cell-free virus. When HFV proviruses were put under the control of a heterologous promoter (simian virus 40), none of the accessory gene products was found to be required for expression of structural (gag) proteins. There was no evidence for a posttranscriptional regulatory protein that is present in other complex retroviruses.
Subject(s)
DNA-Binding Proteins/genetics , Genes, Viral , Open Reading Frames , Retroviridae Proteins/genetics , Spumavirus/genetics , Trans-Activators/genetics , Base Sequence , Blotting, Western , DNA-Binding Proteins/analysis , DNA-Binding Proteins/metabolism , Fibroblasts , Fluorescent Antibody Technique , Genome, Viral , Humans , Molecular Sequence Data , Mutagenesis, Site-Directed , Oligodeoxyribonucleotides , Promoter Regions, Genetic , Restriction Mapping , Retroviridae Proteins/analysis , Retroviridae Proteins/metabolism , Simian virus 40/genetics , Spumavirus/physiology , Trans-Activators/analysis , Trans-Activators/metabolism , Virus ReplicationABSTRACT
Haemolysis caused by influenza viruses is known to occur below pH 6; the pH-optimum for each virus strain is different. Clear dose-effect correlations were found to prevail between the amount of haemolysis and virus concentration. Antibody-mediated inhibition of haemolysis has been investigated with the strain A/PR/8/34 (H1N1) and the recombinant X-73 (H3N2). Inhibition of haemolysis by antisera against different influenza. A virus subtypes suggests that haemolysis inhibiting antibodies are not identical with haemagglutination inhibiting antibodies. The action of antibodies directed against host-cell specific components was excluded by adsorption procedures. Haemolysis inhibiting antibodies are thought to be directed against antigenic determinants of the haemagglutinin functioning as fusion factor.
