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Research paper thumbnail of Membranotropic effects of peptides from the V3 loop of HIV-1

Letters in Peptide Science, 1998

The V3 loop from HIV-1 envelope glycoprotein gp120 is involved in viral entry and determines the ... more The V3 loop from HIV-1 envelope glycoprotein gp120 is involved in viral entry and determines the cellular tropism and HIV-1-induced cell-cell fusion. Earlier we have shown that V3 loop peptides representing the sequences of syncytia-inducing HIV strains have high membranotropic activity. These peptides caused the lysis of liposomes of various lipid compositions, could fuse negatively charged liposomes and induced hemolysis of erythrocytes. In contrast, peptides mimicking the sequences of non-syncytia-inducing viruses showed no lytic or fusion activities at the same concentrations. Now we have found that the V3 loop synthetic peptides containing the conserved GPGR region, derived from T-lymphotropic strains (BRU and MN), as opposed to peptides containing the GPGQ region, are able to cause a pronounced membrane permeabilization (dissipation of the pH and the ψ) of human peripheral blood lymphocytes, erythrocytes and plasma membrane vesicles at micromolar concentrations with a dose-dependent kinetics. Analysis of the secondary structures of the peptides by circular dichroism revealed conformational changes in V3 loop peptides depending on solvent hydrophobicity: from random coil in water to an α-helix/β-sheet conformation in trifluoroethanol. Such structural changes of the V3 loop together with the membrane insertion of the gp41 N-terminal fusion peptide may promote the formation of the fusion pore during virus-cell fusion.

Research paper thumbnail of Sa.55. Development of an Assay to Detect IL-4δ2

Clinical Immunology, 2006

Research paper thumbnail of Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin alpha interactions as a novel HIV-1 therapy

Biochemical and biophysical research communications, Jan 20, 2009

The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodefic... more The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin alpha, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin alpha interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin alpha interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular facto...

Research paper thumbnail of Sa.55. Development of an Assay to Detect IL-4d2

Research paper thumbnail of Su.14. Immunostimulatory Activity of Fullerene Derivatives

Clinical Immunology, 2008

Aim: The Aimstudy was designed to assess the effect of short-term antiretroviral therapy (ART) on... more Aim: The Aimstudy was designed to assess the effect of short-term antiretroviral therapy (ART) on IgA, IgG and IgM and CD4 +T cell count in HIV seropositive subjects. Method: 20 confirmed HIV seropositive subjects, aged between 15-65 years were recruited for the study. They were on triple combinations therapy consisting zidovudine, lamivudine and nevirapine. 20 HIV seronegative subjects were used as control. Blood sample was collected from the participants for the determination of the above parameters in both groups. Result: The CD4 + T cell counts show no significant difference between pre-ART and 2 months post-ARD (P N 0.05) but was significantly higher by 4 months post-ART compared with the pre-ART (p b 0.05). IgG and IgM serum levels showed significantly high values by 2 and 4 months post-ART compared with the pre-ART value (p b 0.05 in each case). However, the serum IgA level by 4 months post-ART showed no significant difference compared with pre-ARD value (p N 0.05). Meanwhile there were no significant differences in CD4 count, IgM, IgA, and IgG levels between 4 months post-ART values compared with the corresponding values in HIV seronegative control subjects. Discussion and conclusion: The present study showed an improvement in the blood concentration of CD4 cell by 4 months post-ART administration, which suggests possible recovery of cellular immunity. The insignificant difference in IgA concentration within the study period possibly suggests non progressive mucosal or sub mucosal infections. Similarly the raised IgM and IgG concentrations within the study period may be an indication of existing infections and signifies possible potentials towards short term recovery. This shows that with the use of these drugs prognosis seem good for the short term.

Research paper thumbnail of Penetration of fullerene C60 derivatives through biological membranes

Fullerenes, …, 2008

Penetration of fullerene C60 in hydrated molecular‐colloidal form (FMC) and various C60 water‐sol... more Penetration of fullerene C60 in hydrated molecular‐colloidal form (FMC) and various C60 water‐soluble derivatives (FDs) through membranes of human erythrocytes, platelets and symbiosomes (subcellular organelles of plant origin) were tested. The FDs ...

Research paper thumbnail of Membranotropic effects of peptides from the V3 loop of HIV-1

Letters in Peptide Science, 1998

The V3 loop from HIV-1 envelope glycoprotein gp120 is involved in viral entry and determines the ... more The V3 loop from HIV-1 envelope glycoprotein gp120 is involved in viral entry and determines the cellular tropism and HIV-1-induced cell-cell fusion. Earlier we have shown that V3 loop peptides representing the sequences of syncytia-inducing HIV strains have high membranotropic activity. These peptides caused the lysis of liposomes of various lipid compositions, could fuse negatively charged liposomes and induced hemolysis of erythrocytes. In contrast, peptides mimicking the sequences of non-syncytia-inducing viruses showed no lytic or fusion activities at the same concentrations. Now we have found that the V3 loop synthetic peptides containing the conserved GPGR region, derived from T-lymphotropic strains (BRU and MN), as opposed to peptides containing the GPGQ region, are able to cause a pronounced membrane permeabilization (dissipation of the pH and the ψ) of human peripheral blood lymphocytes, erythrocytes and plasma membrane vesicles at micromolar concentrations with a dose-dependent kinetics. Analysis of the secondary structures of the peptides by circular dichroism revealed conformational changes in V3 loop peptides depending on solvent hydrophobicity: from random coil in water to an α-helix/β-sheet conformation in trifluoroethanol. Such structural changes of the V3 loop together with the membrane insertion of the gp41 N-terminal fusion peptide may promote the formation of the fusion pore during virus-cell fusion.

Research paper thumbnail of Sa.55. Development of an Assay to Detect IL-4δ2

Clinical Immunology, 2006

Research paper thumbnail of Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin alpha interactions as a novel HIV-1 therapy

Biochemical and biophysical research communications, Jan 20, 2009

The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodefic... more The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin alpha, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin alpha interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin alpha interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular facto...

Research paper thumbnail of Sa.55. Development of an Assay to Detect IL-4d2

Research paper thumbnail of Su.14. Immunostimulatory Activity of Fullerene Derivatives

Clinical Immunology, 2008

Aim: The Aimstudy was designed to assess the effect of short-term antiretroviral therapy (ART) on... more Aim: The Aimstudy was designed to assess the effect of short-term antiretroviral therapy (ART) on IgA, IgG and IgM and CD4 +T cell count in HIV seropositive subjects. Method: 20 confirmed HIV seropositive subjects, aged between 15-65 years were recruited for the study. They were on triple combinations therapy consisting zidovudine, lamivudine and nevirapine. 20 HIV seronegative subjects were used as control. Blood sample was collected from the participants for the determination of the above parameters in both groups. Result: The CD4 + T cell counts show no significant difference between pre-ART and 2 months post-ARD (P N 0.05) but was significantly higher by 4 months post-ART compared with the pre-ART (p b 0.05). IgG and IgM serum levels showed significantly high values by 2 and 4 months post-ART compared with the pre-ART value (p b 0.05 in each case). However, the serum IgA level by 4 months post-ART showed no significant difference compared with pre-ARD value (p N 0.05). Meanwhile there were no significant differences in CD4 count, IgM, IgA, and IgG levels between 4 months post-ART values compared with the corresponding values in HIV seronegative control subjects. Discussion and conclusion: The present study showed an improvement in the blood concentration of CD4 cell by 4 months post-ART administration, which suggests possible recovery of cellular immunity. The insignificant difference in IgA concentration within the study period possibly suggests non progressive mucosal or sub mucosal infections. Similarly the raised IgM and IgG concentrations within the study period may be an indication of existing infections and signifies possible potentials towards short term recovery. This shows that with the use of these drugs prognosis seem good for the short term.

Research paper thumbnail of Penetration of fullerene C60 derivatives through biological membranes

Fullerenes, …, 2008

Penetration of fullerene C60 in hydrated molecular‐colloidal form (FMC) and various C60 water‐sol... more Penetration of fullerene C60 in hydrated molecular‐colloidal form (FMC) and various C60 water‐soluble derivatives (FDs) through membranes of human erythrocytes, platelets and symbiosomes (subcellular organelles of plant origin) were tested. The FDs ...