Biomedical subjects

W Kamp

Publications and source records attributed to W Kamp.

12 recordsLinked to original sources

PubMed2004

Multiple effects of HIV-1 trans-activator protein on the pathogenesis of HIV-1 infection.

The HIV-1 trans-activator (Tat) protein is proposed as an important factor in the complex HIV-induced pathogenesis of AIDS. In this paper, multiple effects of this viral protein are described. Originally discovered as an intracellular activator of HIV-1 transcription, Tat was found to regulate viral reverse transcription as well. Trans-activator was found to be secreted by HIV-infected cells and taken up by neighbouring cells. In this way, Tat is able to affect both infected and uninfected cells. Intracellularly, Tat can deregulate the expression of several heterologous cellular and viral genes. Extracellular Tat can contribute to the spreading of HIV-1 and immunosuppression of uninfected cells. Finally, there is evidence that exogenous Tat is involved in AIDS-associated pathologies such as Kaposi's sarcoma and HIV-associated dementia. These capacities together accelerate the progression towards AIDS and make Tat an interesting candidate as a constituent of an anti-AIDS vaccine.

AIDS Dementia Complex↗

PubMed2001

Interactions between major histocompatibility complex class II surface expression and HIV: implications for pathogenesis.

Although it has been almost 20 years since the first cases of acquired immunodeficiency syndrome (AIDS) were documented, the pathogenesis is still not completely understood. Interactions between major histocompatibility complex (MHC) Class I and human immunodeficiency virus (HIV), resulting in down-regulation of MHC-I surface expression, have been reported to contribute to pathogenesis by suppressing the host's immune response. Interactions between MHC Class II and HIV have also been described, but it is unclear how these contribute to the pathogenesis. MHC-II surface expression on HIV-infected monocytes and monocytic cell lines has been described to be increased as well as decreased when compared to uninfected control monocytes. HIV-specific mechanisms appear to down-regulate MHC-II expression on blood monocytes during HIV-1 infection, whereas host mechanisms up-regulate MHC-II expression in response to infection of blood monocytes as well as brain macrophages. A balance between these two may determine MHC-II expression levels in individual patients. Altogether, HIV seems to be able to benefit from both low and high levels of MHC-II surface expression. The first results in reduced immune surveillance of the host, allowing the virus to replicate faster; the second increases infectivity of the virus as a result of higher MHC-II density on macrophages and virion particles.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Mechanisms of HIV-1 to escape from the host immune surveillance.

Since the beginning of the acquired immune deficiency syndrome (AIDS) pandemic in 1981, research on human immunodeficiency virus (HIV) has been focused on mechanisms by which the virus escapes from immune surveillance. Several human leucocyte antigen haplotypes have been shown to be associated with rapid disease progression or resistance to disease progression. In addition, HIV is able to down-regulate major histocompatibility complex type I (MHC-I) on the surface of the host cell. For this down-regulation HIV seems to use three different mechanisms mediated by three different viral proteins. The viral Tat protein represses transcription of the MHC-I, Vpu retains nascent MHC-I chains in the endoplasmic reticulum and Nef mediates selective internalization of MHC-I molecules from the plasma membrane. The last mechanism also provides protection to natural killer cells that attack cells with little or no MHC-I on the cell surface. Together these mechanisms provide a very efficient escape from the host immune system.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Effect of weekly adefovir (PMEA) infusions on HIV-1 virus load: results of a phase I/II study.

The compound 9-(2-phosphonylmethoxyethyl)adenine (adefovir; PMEA) is a potent inhibitor of a number of viruses in vitro, such as human immunodeficiency virus (HIV) type 1 and 2, herpes simplex virus (HSV) type 1 and 2, human papillomavirus virus (HBV) and Epstein-Barr virus (EBV). Adefovir also proved to be effective in vivo against feline immunodeficiency virus (FIV) in cats and simian immunodeficiency virus (SIV) in rhesus monkeys. In an open, non-placebo-controlled trial the antiviral activity of weekly doses of adefovir in nine patients with AIDS or AIDS-related complex was studied for a period of 11 weeks. CD4 cell counts at baseline were between 10 and 450 cells/mm3, HIV-1 RNA levels at baseline were between 24,210 copies/ml and 406,197 copies/ml. The drug was administered intravenously at a dose of 1000 mg every week and plasma viral load was assessed at multiple points during the study. Administration of adefovir was tolerated well and no severe side effects were seen. The response to adefovir treatment differed widely between patients. The increase in CD4 cell count at end point ranged from -40 to 120 cell/mm3. The lowest HIV RNA levels were measured after 3-5 days, showing an increase thereafter. The nadir in viral load was achieved after 2 weeks, with a mean viral load decline of 0.7 from baseline. The decrease of the HIV RNA level at end point ranged from -0.3 log10 to 1.8 log10 with a mean decrease of 0.4 log10. Our results indicate that adefovir given intravenously once weekly has a short-lasting initial antiviral effect. The effect of more frequent dosing requires further evaluation. If adefovir is to be useful clinically, it needs to be combined with other antiviral agents.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Safety of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in patients with human immunodeficiency virus infection: a pilot study.

The compound 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent inhibitor of a number of viruses in vitro such as human immunodeficiency virus types 1 and 2, herpes simplex virus types 1 and 2, hepatitis B virus, cytomegalovirus, and Epstein-Barr virus. PMEA also proved to be effective in vivo against feline immunodeficiency virus in cats and simian immunodeficiency virus in rhesus monkeys. In an open, non-placebo-controlled trial, the safety of weekly doses of PMEA in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was studied for a period of 11 weeks. CD4+ T-cell counts at baseline were between 10 and 450/mm(3). The drug was administered intravenously at a dose of 1000 mg. No serious side-effects were seen. On one occasion one patient showed alanine aminotransferase and aspartate aminotransferase levels 5 times higher than the upper limit of normal and another patient showed on one occasion aspartate aminotransferase levels 5 times higher than the upper limit of normal. In another patient serum amalyse levels increased, on one occasion 1.5 times above the upper limit of normal. An improvement in general well-being was reported by all patients. For patients with a CD4+ T-cell count > 100/mm(3) at baseline, the CD4+ T-cell count increased from a mean of 283/mm(3) at baseline to a mean of 448/mm(3) at the end of the study. Repeat infusions of PMEA at a dose of 1000 mg were safe and well tolerated. Our results suggest that PMEA, administrated according to this treatment schedule, may be effective in treating patients with human immunodeficiency virus infection.

AIDS-Related Complex↗

PubMed1988