Biomedical subjects
Publications and source records attributed to Veljko Veljkovic.
Flavonoid compounds represent an important natural source of antiretrovirals for AIDS therapy due to their significant anti-HIV-1 activity and low toxicity. Here we propose a simple theoretical criterion to discriminate active from inactive flavonoids that is suitable for rapid in silico screening of flavonoid libraries, and selection and optimization of lead compounds with anti-HIV-1 activity.
It has been reported that antibodies reactive with peptide RSANFTDNAKTIIVQLNQSVEIN (peptide NTM) derived from the C-terminus of the second conserved domain of HIV-1 envelope glycoprotein gp120 could represent an important factor in control of the HIV disease. In order to check this notion we (i) tested reactivity with peptide NTM serum samples collected from 310 consecutive HIV-1 infected patients with a CD4(+) lymphocyte count ranging from 10 to 800/microL and (ii) performed the longitudinal study that included 107 sera samples collected from 29 HIV patients. Results of these studies demonstrated correlation between presence of anti-NTM antibodies in sera of HIV patients and disease progression measured by the CD4(+) cell count. Based on these findings we proposed the anti-NTM antibodies as useful prognostic marker for HIV disease.
Research and clinical data reported during last 10 years indicate the possibility that AIDS vaccines based on the HIV-1 envelope protein gp120 may be worse then useless. A correct assessment of the safety of these AIDS vaccines can not be possible without data which will allow comparison of the disease status between breakthrough HIV infected vaccinated volunteers and those from the control group. Results of the recently finished clinical trial of AIDSVAX represent a good base for this important analysis.
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This overview briefly summarizes the current status of global AIDS epidemic, especially pointing out how this pandemic looked in the last year of the second millennium. We also give a brief overview of the state of the art in development of AIDS vaccines together with a short summary of the supporting data and obstacles in this development.
A broad range of structural, functional, and immunological similarities between HIV-1 gp120 and human proteins, especially those participating in immune responses, highlight gp120 as a pleiotropic protein that can in different ways affect many important functions of the human immune system. Here we described some of these properties of HIV-1 gp120 that represent the main obstacle in the development of effective and safe AIDS vaccine.
It has been demonstrated that the immunodominant V3 loop of HIV-1 gp120 and its flanking regions bear sequence and structural homology to the framework and complementarity-determining regions of human immunoglobulins. It has been proposed that the Ig-like domain of gp120 might encode idiotypes and in this way permit HIV-1 entry into the immune regulatory network. This notion is strongly supported by results demonstrating that the anti-V3 loop and anti-Ig antibodies of healthy individuals share complementary structure and that V3 reactive antibodies are present in HIV-negative sera. This might be the mechanism by which HIV induces immunological abnormalities, and it should be taken into consideration in AIDS vaccine development.
In sera of HIV-infected individuals natural antibodies recognizing nonimmunogenic C-terminal domain of the second conserved region of HIV-1 gp120 and the vasoactive intestinal peptide (VIP) were identified. It has been demonstrated that these antibodies are significantly more prevalent in asymptomatic carriers than in AIDS patients and that their titer strongly correlates with disease progression. These findings point out the VIP/C2-reactive natural antibodies as an important agent for immunotherapy of HIV disease.
Using a chimeric primer consisting of the nucleotide sequence derived from the HIV-1 envelope gene coding for the second conserved region of gp120, and the highly conserved sequence derived from the human immunoglobulin gene coding for the VHIII domain, it has been identified in sera of AIDS patients HIV-1 field isolates carrying the complete and active Chi recombination hot spot (GCTGGTGG). The recombination between the HIV-1 gene coding for the central portion of gp120 and the bacterial gene coding for the clp protease was also demonstrated in vivo. These results point out serious concern that vectored AIDS vaccine candidates carrying the HIV-1 env gene on viral and bacterial vectors could become the source of potentially new infectious diseases rather than an effective instrument for AIDS prevention.
It has been demonstrated that HIV-1 gp120 resembles several important properties of immunoglobulins allowing it strong influence on the human immune system, especially through induction of the deceptive imprinting and deregulation of the immune network. On the other hand there are many unanswered questions concerning properties and control of the genetically modified viruses and bacteria used as vectors in AIDS vaccines. This situation opens a serious question about the safety of vectored AIDS vaccine and the ethics of their trials in humans.