Mechanism of human immunodeficiency virus-induced complement expression in astrocytes and neurons.

The cerebral complement system is hypothesized to contribute to neurodegeneration in the pathogenesis of AIDS-associated neurological disorders. Our former results have shown that the human immunodeficiency virus (HIV) strongly induces the synthesis of complement factor C3 in astrocytes. This upregulation explains in vivo data showing elevated complement levels in the cerebrospinal fluid of patients with AIDS-associated neurological symptoms.

Neuroinvasion by pathogens: a key role of the complement system.

Complement (C) is one of the most critical defence mechanisms of the innate immunity against cerebral infection by viruses, bacteria and fungi, with different molecular pathways contributing to the clearance of the invading pathogens. There is now compelling evidence that C proteins can be synthesized by brain cells in response to the infectious challenge and leading to cytotoxic and cytolytic activities against the harmful intruders. However, since there is also emerging evidence that uncontrolled C biosynthesis/activation can lead to brain inflammation with loss of neurons and oligodendrocytes, it is important to highlight that C may have adverse effects in infectious diseases of the CNS and induce profound tissue damage.

Residential status and HIV risk behaviors among Puerto Rican drug injectors in New York and Puerto Rico.

This article investigates the association between residential status and human immunodeficiency virus (HIV) risk behaviors among island and New York Puerto Rican injection drug users (IDUs). We assigned 561 subjects from New York City and 312 from Puerto Rico to five residential status categories: living in parent's home, living in own home, living in other's home, living in temporary housing (hotel, single-room occupancy [SRO] hotels), and homeless (living in streets/shelters). Dependent variables included injection- and sex-related risk behaviors (sharing syringes, sharing other injection paraphernalia, shooting gallery use, and having paid sex).

Complement-dependent control of viral dynamics in pathogenesis of human immunodeficiency virus and simian immunodeficiency virus infection.

Since the first contact with the host, human immunodeficiency virus (HIV) exploits the complement system to reach maximal spread of infection. HIV has adapted many strategies to avoid complement-mediated lysis and uses the opsonization with complement fragments for attachment to complement receptors (CR). From the pathogen's perspective, binding to CR-expressing cells is remarkably beneficial, bringing together virus and activated target cells that are highly susceptible to infection.

Induction of apoptosis by 7,8-dihydroneopterin: involvement of radical formation.

Interferon-gamma is a cytokine released in large amounts during cell-mediated immune response. It induces the expression of proinflammatory cytokines and enhances macrophage capacity to secrete reactive oxygen intermediates and the pteridines neopterin and 7,8-dihydroneopterin. To assay the role of these pteridines in the immune system several studies were performed.

Human immunodeficiency virus type 1 induces expression of complement factors in human astrocytes.

Since the brain is separated from the blood immune system by a tight barrier, the brain-resident complement system may represent a central player in the immune defense of this compartment against human immunodeficiency virus (HIV). Chronic complement activation, however, may participate in HIV-associated neurodegeneration. Since the level of complement factors in the cerebrospinal fluid is known to be elevated in AIDS-associated neurological disorders, we evaluated the effect of HIV type 1 (HIV-1) on the complement synthesis of brain astrocytes.

An alternative program for methadone maintenance dropouts: description and preliminary data.

Time in drug treatment has been shown to be one of the best predictors of post-treatment success. Since as many as half of the enrollees leave methadone treatment during the first year, the project described in this article was designed to test the effectiveness of an alternative program for individuals who have recently dropped out of methadone maintenance treatment. The goals of this "Alternative Program" are to help participants re-connect with formal drug treatment and other community or medical programs, reduce their HIV risk behavior, decrease or eliminate drug use, join self-help groups, and obtain entitlements.

Network-related mechanisms may help explain long-term HIV-1 seroprevalence levels that remain high but do not approach population-group saturation.

In many cities, human immunodeficiency virus (HIV)-1 seroprevalence among drug injectors stabilizes at 30-70% for many years without secondary outbreaks that increase seroprevalence by 15% or more. The authors considered how HIV-1 incidence can remain moderate at seroprevalence levels that would give maximum incidence. Previously suggested answers include behavioral risk reduction and network saturation within high-risk subgroups.

Pretest assessment as a component of safer sex intervention: a pilot study of brief one-session interventions for women partners of male injection drug users in New York City.

This pilot study evaluated whether brief safer sex interventions for women partners of male injection drug users significantly influenced perceptions of partner risk, human immunodeficiency virus (HIV) knowledge, correct condom usage, and self-reported consistent safer sex (abstinence or 100% of vaginal-penile intercourse acts protected by male or female condoms). The study also examined the impact of pretest assessment on those variables since pretest assessment may challenge participants' current knowledge, safer sex practices, and partner communication techniques. The study randomly assigned participants to pretest or no pretest assessment.

Histamine suppresses neopterin production in the human myelomonocytoma cell line THP-1.

Histamine, an important inflammatory mediator in allergic diseases and asthma, was reported to have modulatory effects on T cells by down-regulating Th1-type cell cytokines like interleukin 2 (IL-2) and interferon-gamma (IFN-gamma). In this study we examined the effect of histamine and the histamine-receptor antagonists cimetidine and diphenhydramine on the production of neopterin after stimulation with IFN-gamma in the myelomonocytoma cell line THP-1. Increasing concentrations of histamine markedly suppressed IFN-gamma induced neopterin formation.

HIV-1 envelope protein gp41 modulates expression of interleukin-10 and chemokine receptors on monocytes, astrocytes and neurones.

Objective: To analyse the effect of HIV-1 transmembrane protein gp41 on cytokine production and chemokine receptor expression in blood and brain.

Design: Because previous results had demonstrated that recombinant gp41 contributes to HIV-induced dysfunction of blood immune cells we investigated its effect on interleukin (IL)-10 synthesis and expression of the HIV coreceptors CCR5 and CXCR4 in different human brain cells.

Methods: Astrocytic, microglial and neuronal cell lines were incubated with the extracellular domain of gp41 (aa565-647).

Dissimilar attenuation of Candida albicans virulence properties by human immunodeficiency virus type 1 protease inhibitors.

The secreted aspartyl proteinase (Sap) of Candida albicans, which is believed to represent an important virulence factor of this opportunistic yeast, and the human immunodeficiency virus type 1 (HIV-1) protease, which is obligatory for the production of infectious virions, both belong to the same family of aspartyl proteinases. We have previously shown that the HIV-1 protease inhibitor Indinavir directly inhibits secretion and proteinase activity of Sap in a dose-dependent manner. Furthermore, at very high concentrations, viability of C.

A 60 kD heat-shock protein-like molecule interacts with the HIV transmembrane glycoprotein gp41.

The heat-shock protein hsp60 is typically found in mitochondria, but, in smaller amounts, also in the cell cytoplasm and associated with the cell membrane. Since heat-shock proteins are known to interact with a variety of molecules and since purified HIV-1 particles were described to contain hsp60 molecules, we tested the possibility that a previously described putative receptor for HIV transmembrane protein gp41 is identical to hsp60. The gp41-binding human protein P62 was purified from H9 and Raji cell lysates by a gp41-coupled affinity column.

Modulation of cell surface protein expression by infection with HIV-1.

The examples discussed above show the profound influence of HIV infection on expression pattern of cell surface proteins and the functional relevance thereof. Altered cell surface pattern is involved in all aspects of HIV-induced pathogenesis such as viral spreading viral adhesion and cellular apoptosis and is an important parameter for therapeutical approaches. The regulatory mechanism is not homogenous for all proteins but includes divergent effects like modulation of gene transcription and proteolytic cleavage.

Human immunodeficiency virus type 1 derived from cocultures of immature dendritic cells with autologous T cells carries T-cell-specific molecules on its surface and is highly infectious.

During the budding process, human immunodeficiency virus type 1 (HIV-1) acquires cell surface molecules; thus, the viral surface of HIV-1 reflects the antigenic pattern of the host cell. To determine the source of HIV-1 released from cocultures of dendritic cells (DC) with T cells, immature DC (imDC), mature DC (mDC), T cells, and their cocultures were infected with different HIV-1 isolates. The macrophage-tropic HIV-1 isolate Ba-L allowed viral replication in both imDC and mDC, whereas the T-cell-line-tropic primary isolate PI21 replicated in mDC only.

The network approach and interventions to prevent HIV among injection drug users.

Objective: To review human immunodeficiency virus (HIV) risk reduction interventions among injecting drug users (IDUs) that have adopted a network approach.

Methods: The design and outcomes of selected network-based interventions among IDUs are reviewed using the network concepts of the dyad (two-person relationship), the personal risk network (an index person and all of his or her relationship), and the "sociometric" network (the complete set of relations between people in a population) and community.

Results: In a dyad intervention among HIV-serodiscordant couples, many of which included IDUs, there were no HIV seroconversions.

HIV serostatus and risk behaviors in a multisite sample of drug users.

In developing HIV prevention efforts, it is critical to determine whether interventions are effective in achieving declines in risk behavior among both HIV-positive and HIV-negative individuals. Based on a multisite intervention study of injection drug users (IDUs) and crack smokers, 488 seropositive IDUs and 364 seropositive crack users were compared with randomly selected matched samples of seronegatives (with matching based on recruitment site, gender, age group and ethnicity) at baseline and six-month follow-up to compare changes in risk behaviors by serostatus. Results indicated that overall, risk behaviors declined substantially over time; significant interaction effects indicated that seropositives reported a greater decline in sex risk behaviors than seronegatives.

Neopterin derivatives modulate the nitration of tyrosine by peroxynitrite.

The impact of neopterin and 7,8-dihydroneopterin on peroxynitrite-induced nitration of l-tyrosine was studied. Neopterin derivatives and peroxynitrite are formed during immune response. Tyrosine nitration represents one major effect of nitric oxide-mediated cytotoxicity.

Predictors of HIV infection among women drug users in New York and Miami.

In the US, the number of women diagnosed with AIDS continues to increase. In this study, women in New York City (East Harlem) and Miami, two sites with high rates of drug use and HIV infection, were first compared on sociodemographic variables and risk behaviors. Logistic regression analyses were used to identify significant, independent predictors of HIV infection in each city.

gp41 envelope protein of human immunodeficiency virus induces interleukin (IL)-10 in monocytes, but not in B, T, or NK cells, leading to reduced IL-2 and interferon-gamma production.

The effect of extracellular domain of human immunodeficiency virus (HIV-1) transmembrane glycoprotein gp41 on interleukin (IL)-10, IL-2, interferon (IFN)-y, IL-4, and tumor necrosis factor-alpha production by human peripheral blood mononuclear cells (PBMC) was assessed by ELISA. Rapid gp41-induced increase of IL-10 production was detected in resting PBMC and isolated monocytes but not in B, T, or NK cells. Furthermore, gp41 also enhanced IL-10 production in staphylococcal enterotoxin B-stimulated PBMC, while synthesis of IL-2, IFN-gamma, and IL-4 in these cells was down-modulated.

Correlates and distribution of HIV risk behaviors among homeless youths in New York City: implications for prevention and policy.

Homeless youths are at high risk for poor health outcomes, including repeated exposure to STDs and high rates of unplanned pregnancies, untreated TB, HIV infection, and accelerated immune dysfunction associated with AIDS. This article examines the nature and distribution of HIV-risk behavior in a broad, street-based sample of homeless and runaway youths in New York City (N = 929). Although street youths in general are shown at high risk, the highest risks nest within older age segments of the male street youth population.

Streptococcal erythrogenic toxins induce tryptophan degradation in human peripheral blood mononuclear cells.

Background: In various cells including monocytes the cytokine interferon-gamma as well as lipopolysaccharide induce indoleamine 2,3-dioxygenase which degrades tryptophan to form L-kynurenine. We addressed the question of whether the exposure of human peripheral mononuclear cells to superantigens derived from streptococci is associated with tryptophan degradation in vitro.

Methods: Peripheral blood mononuclear cells were exposed to streptococcal erythrogenic toxins A and B and a streptococcal-derived mitogen named BX.

Acquisition of host cell-surface-derived molecules by HIV-1.

Objective: To determine the acquisition of host cell-membrane-derived molecules by HIV-1 during the budding process, and to investigate whether the uptake of these molecules is cell-type-specific and selective.

Design: Virions, propagated by four different cell types were analysed for the presence of adhesion molecules, glycosylphosphatidylinositol (GPI)-anchored proteins and various cell-surface markers. The pattern was compared with the phenotype of the HIV-1-infected cell.

HIV-1 gp41 selectively inhibits spontaneous cell proliferation of human cell lines and mitogen- and recall antigen-induced lymphocyte proliferation.

Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein 41 (gp41) contains an immunosuppressive domain (Env amino acids 583-599). Previous studies by us and others using recombinant soluble gp41 (rsgp41; amino acids 539-684) and immunosuppressive peptide (1SP; a gp41 peptide, amino acids 583-599) have shown that HIV-1 gp41 by the immunosuppressive domain could bind to several proteins on human T, B and monocyte cell lines, and also to normal human peripheral blood mononuclear cells. In this study we demonstrated that HIV-1 rsgp41 could inhibit spontaneous cell proliferation of human T cell lines H9 and Jurkat, B cell lines Raji and Daudi, monocyte cell line U937, but could not inhibit cell proliferation of human fibroblast cell line HEF and green monkey kidney cell line Cos-1.

Human complement proteins C3b, C4b, factor H and properdin react with specific sites in gp120 and gp41, the envelope proteins of HIV-1.

Recently we reported the basic phenomenon of an interaction between the envelope glycoproteins of HIV-1 gp120 and gp41 and components of the human complement system, i.e. activated C4 (C4b) and activated C3 (C3b) and the complement regulator proteins factor H and properdin.