New Approach for Inhibition of HIV Entry: Modifying CD4 Binding Sites by Thiolated Pyrimidine Derivatives.

Thiolated pyrimidine derivatives have been synthetized and their antiretroviral effect against human immunodeficiency virus type 1 (HIV-1IIIB) and HIV-1 chimeric pseudovirions have been quantitatively determined in cell-based viral infectivity assays including syncytium inhibition assay as well as a single-cycle viral infection assay on HeLaCD4-LTR/ß-gal cells. Pseudotype virions prepared bearing HIV-1 envelope preference for CCR5 coreceptor, CXCR4 coreceptor or for both, respectively, with a HIV-1 core containing luciferase reporter gene were able to infect susceptible cells but are replication defective so unable to replicate in the cells . Data indicate that thiolated pyrimidine derivatives inhibited effectively virally induced cell fusion in vitro as well as infectivity of primary HIV-1IIIB strain and HIV-1 pseudovirions using chemokine receptors CCR5 or CXCR4 or both for virus entry a dose dependent manner.

Thiolated pyrimidine nucleotides may interfere thiol groups concentrated at lipid rafts of HIV-1 infected cells.

Upon HIV infection, cells become activated and cell surface thiols are present in increased number. Earlier we demonstrated in vitro anti-HIV effect of thiolated pyrimidine nucleotide UD29, which interferes thiol function. To further analyse the redox processes required for HIV-1 entry and infection, toxicity assays were performed using HIV-1 infected monolayer HeLaCD4-LTR/ β-gal cells and suspension H9 T cells treated with several thiolated nucleotide derivatives of UD29.

Antiretroviral effect of 4-thio-uridylate against human immunodeficiency virus type 1.

Antiretroviral effect of thiolated nucleotide 4-thio-uridylate (S4UMP, designated as UD29) against human immunodeficiency virus type 1 (HIV-1) have been quantitatively determined in cell-based viral infectivity assays. In syntitium inhibition assay on MT-2 human T-cell line UD29 prevented cell fusion and formation of syntitia induced by HIV-1IIIB with IC50 values of 11.7 μg/ml.

Thermus composti sp. nov., isolated from oyster mushroom compost.

A Gram-stain-negative, rod-shaped bacterium (strain K-39(T)) was isolated from the thermophilic phase of the composting process for oyster mushroom substrate preparation. The strain grew at 40-80 °C (optimum, 65-75 °C), at pH 5-9 (optimum, pH 7), in media containing up to 1.5% (w/v) NaCl.

The Consequence of a Founder Effect: CCR5-∆32, CCR2-64I and SDF1-3'A Polymorphism in Vlach Gypsy Population in Hungary.

Frequencies of genetic polymorphisms of the three most frequent HIV-1 resistance-conferring alleles playing an important role in HIV-1 pathogenesis were analysed in Vlach Gypsy populations living in Hungary, as the largest minority. Mutations in the encoding genes, such as CCR5-∆32, CCR2-64I and SDF1-3'A are shown to result in protective effects against HIV-1 infection and disease progression. 560 samples collected from Vlach Gypsy individuals living in 6 North-East Hungarian settlements were genotyped by PCR-RFLP method.

Monitoring of drug resistance in therapy-naïve HIV infected patients and detection of African HIV subtypes in Hungary.

Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naïve Hungarian individuals transmitted as primary infection by their foreign sexual partners originated from African, Asian and other European countries had been analyzed. Drug resistance genotyping of HIV RT and PR genes were performed where mutations of 72 codons - among them 64 specific resistance codons representing 6 nucleoside reverse transcriptase inhibitor (NRTIs), 2 non-nucleoside reverse transcriptase inhibitor (NNRTIs) and 6 proteinase inhibitor (PRIs) drugs - had been analyzed by Truegene HIV-1 Genotyping kit and OpenGene Sequencing System. Viral variants harboring resistance mutations in the po l gene were detected in 14% of the subjects.

Molecular detection of T. pallidum by PCR in seronegative cases.

For the molecular detection of Treponema pallidum authors introduced and used a nested PCR amplifying a conservative portion of the gene coding for the Tp 47 kDa membrane protein. PCR verified the presence of T. pallidum specific DNA in 5.