Functional evaluation of DC-SIGN monoclonal antibodies reveals DC-SIGN interactions with ICAM-3 do not promote human immunodeficiency virus type 1 transmission.

DC-SIGN, a type II membrane-spanning C-type lectin that is expressed on the surface of dendritic cells (DC), captures and promotes human and simian immunodeficiency virus (HIV and SIV) infection of CD4(+) T cells in trans. To better understand the mechanism of DC-SIGN-mediated virus transmission, we generated and functionally evaluated a panel of seven monoclonal antibodies (MAbs) against DC-SIGN family molecules. Six of the MAbs reacted with myeloid-lineage DC, whereas one MAb preferentially bound DC-SIGNR/L-SIGN, a homolog of DC-SIGN.

Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity.

Proteoglycans that modulate the activities of growth factors, chemokines, and coagulation factors regulate in turn the vascular endothelium with respect to processes such as inflammation, hemostasis, and angiogenesis. Endothelial cell-specific molecule-1 is mainly expressed by endothelial cells and regulated by pro-inflammatory cytokines (Lassalle, P., Molet, S.

The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1.

The trafficking of leukocytes through tissues is supported by an interaction between the beta 2 (CD18) integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) and their ligand ICAM-1. The most recently identified and fourth member of the beta 2 integrins, alpha D beta 2, selectively binds ICAM-3 and does not appear to bind ICAM-1. We have reported recently that alpha D beta 2 can support eosinophil adhesion to VCAM-1.

ICAM-3 and E-selectin endothelial cell expression differentiate two phases of angiogenesis in infantile hemangiomas.

Cellular adhesion molecules are newly identified mediators of angiogenesis. Infantile hemangiomas, characterized in the early stages by a proliferation of poorly differentiated vessels followed in the late stages by a vascular differentiation and regression of the tumor, represent an interesting model to study angiogenesis. We studied by immunohistochemistry the distribution of HLA-DR and three adhesion molecules ICAM-3, E-selectin and VCAM-1 on endothelial cells in different stages of vessel differentiation in infantile hemangiomas.

Intercellular adhesion molecule-3 on endothelial cells. Expression in tumors but not in inflammatory responses.

Intercellular adhesion molecule-3 (ICAM-3) was identified as the third counter-receptor for lymphocyte function-associated antigen-1. ICAM-3 is absent on endothelial cells in normal tissues but found on endothelial cells in lymphomas. Here, we examined ICAM-3 expression on vascular endothelial cells in lymphomas, nonlymphoid malignancies, benign tumors, and inflammatory diseases.

Expression of ICAM-R (ICAM-3), a novel counter-receptor for LFA-1, in rheumatoid and nonrheumatoid synovium. Comparison with other adhesion molecules.

Objective: To study the distribution of intercellular adhesion molecule receptor (ICAM-R, or ICAM-3), a novel ligand for the leukointegrin lymphocyte function-associated antigen 1 (LFA-1), in normal and rheumatoid synovial membranes and to compare this with the distribution of ICAM-1, ICAM-2, vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1).

Methods: We performed immunohistochemical analyses of frozen sections of normal and rheumatoid synovial tissue using monoclonal antibodies to the molecules examined.

Results: ICAM-1 staining was detectable on the vascular endothelium and the synovial lining cells of both normal and rheumatoid synovial membranes.

[Cerebral lymphoma in AIDS: clinical study and clinicopathological correlations].

We report the natural history of 17 brain lymphomas (11 primary, 6 disseminated) from a post-mortem series of 130 patients with AIDS. Primary lymphomas appeared lately in the course of AIDS. They were often associated with a severe T-cell immunodepression and with more frequent opportunistic disorders than disseminated lymphomas.

HIV-1-associated cognitive/motor complex: absence of neuronal loss in the cerebral neocortex.

We performed a postmortem morphometric study in six AIDS patients and six controls to determine if a neocortical neuronal loss occurs in HIV-1-associated cognitive/motor complex. Patients were selected during a prospective study including psychometric evaluation and neuroimaging, and none had focal lesions. Two had HIV-1-associated myelopathy with mild cognitive impairment, and four had HIV-1-associated dementia complex.

[A neuropathological study of 10 HIV-infected children].

In 10 children infected by HIV at birth, who presented early and severe immunodeficiency encephalopathy, the lesions observed in the central nervous system were different from those found in adults. Using standard neuropathological techniques, the main abnormalities were white matter palor and atrophy, pyramidal tract demyelination, moderate perivascular inflammation, numerous calcifications of blood vessels in basal ganglia, white matter and occasional in the cortex, few opportunistic infections including cytomegalovirus ventriculitis, polymorphonuclear microabcessses and aspergillus abscesses; no toxoplasma was detected. An 18-month-old girl presented with an angiocentric lymphoproliferative disorder in central and peripheral nervous system and muscle, with predominance of B cells.

Cloning and characterization of a new intercellular adhesion molecule ICAM-R.

The human intercellular adhesion molecules ICAM-1, ICAM-2 and their counter-receptors, the beta 2 or leukointegrins, mediate a variety of homotypic and heterotypic leukocyte and endothelial cell-cell adhesions central to immunocompetence. It has been found that cell-cell adhesion which is dependent on expression of the leukocyte function-associated antigen LFA-1 is not always blocked completely by antibodies raised against ICAM-1 and ICAM-2. Other leukointegrin ligands therefore probably exist, such as a glycoprotein of M(r) 124K that binds LFA-1 and has been designated ICAM-3 on the basis of this function.

Detection of human immunodeficiency virus type 2 in brain tissue.

Infection due to human immunodeficiency virus (HIV) type 2 is believed to cause a clinical picture similar to that of HIV-1, although extensive data are not available. In 2 patients with West African exposure and neurologic symptoms, HIV-2 was detected in the central nervous system using DNA and RNA polymerase chain reaction, in situ hybridization, and immunohistology. In the first patient, the neurologic disease was most likely due to productive infection with HIV-2.

Low levels of human immunodeficiency virus replication in the brain tissue of children with severe acquired immunodeficiency syndrome encephalopathy.

The authors examined the autopsy brain samples of nine children infected with human immunodeficiency virus (HIV) at birth by histology, immunologic staining, and in situ hybridization. Surprisingly, although seven of these children presented with typical AIDS encephalopathy, the authors could detect a multifocal HIV infection in the brains of only three of these patients. The authors could not detect any significant HIV replication in the brain of four other children despite severe neurologic disease.

Clinical and virological aspects of HIV2 infection in rhesus monkeys.

To establish an animal model of AIDS, two different "wild" or "adapted" HIV2 Rod and Eho strains were cultivated on monkey cells from different species (baboons, cynomolgus, Rhesus monkeys). Five different available strains were then injected both by intravenous (i.v.

Early viral replication in the brain of SIV-infected rhesus monkeys.

To investigate the mechanism of simian immunodeficiency virus (SIV) entry into the central nervous system (CNS) and the initial events leading to neuropathogenesis, SIV replication was studied by in situ hybridization in the CNS of 5 Rhesus macaques at 7 days, 1, 2, and 3 months after SIV intravenous inoculation. CNS infection was found to be a frequent and early event, as SIV was detected in the CNS of all the animals studied and as early as 7 days postinoculation. At the earliest stage, the infection localized mainly to perivascular cells.

HIV proteins absent from placentas of 75 HIV-1-positive women studied by immunohistochemistry.

Recent epidemiological and virological data suggest that the incidence of maternofetal transmission of HIV-1 infection is between 20 and 30%. The available evidence points to a possible role of peri- and postnatal contamination, but the isolation of HIV from fetuses shows that transplacental transmission also occurs. We attempted to detect, by means of an immunohistochemical method, HIV proteins in frozen placentas from 75 HIV-1-positive women (30 at term, 45 induced abortions).

AIDS encephalopathy and tropism of HIV for brain monocytes/macrophages and microglial cells.

HIV induces severe dementia in about 20% of adult AIDS patients. In children HIV-infected at birth, the incidence of specific neurological complications is still higher since severe encephalopathy occurs in almost all children who develop an early and severe immunosuppression. In all cases, the brain monocytes/macrophages and the microglial cells are the only cells which replicate HIV in the central nervous system (CNS) of these patients, and the appearance of neurological symptoms seems induced by an interaction between HIV-infected macrophages with neurons and glial cells.

Skeletal muscle involvement in human immunodeficiency virus infection.

In addition to muscle changes due to peripheral nervous system involvement, primary myopathic changes associated with the human immunodeficiency virus (HIV) have also been described. We studied seven cases: two had developed an acquired immunodeficiency syndrome (AIDS), four had seroconverted to HIV but were otherwise asymptomatic, one was HIV seronegative when the biopsy was performed and one was biopsied twice. Besides the HIV no other infectious agent was detected.

[AIDS dementia].

Human immunodeficiency virus type I (HIV), the etiology of AIDS is also the cause of a primary infection of the central nervous system. The AIDS Dementia Complex is a common and important cause of morbidity in patients in advanced stages of infection. Subacute encephalitis demonstrating, the neuropathogenicity of HIV 1 constitute an human model for slow virus encephalitis.

Severe encephalitis resulting from coinfections with HIV and JC virus.

We observed 3 cases of progressive multifocal leukoencephalopathy (PML) among frozen CNS samples obtained at autopsy from 102 adult AIDS patients. In 2 patients, PML was associated with severe HIV encephalitis. In those 2 cases, the areas of extensive JC-induced demyelination were massively infiltrated by HIV infected macrophages/microglial cells with evidence for localized increase of HIV encephalitis in PML lesions.

MRI pattern of progressive multifocal leukoencephalopathy (PML) in AIDS. Pathological correlations.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease which occurs in immunodepressed subjects and is particularly frequent in AIDS. Some authors having drawn attention to the protean aspect of the disease and claimed that AIDS may lose its basic characteristics and affect the grey matter as well as the white matter, we reviewed a series of 8 patients who had been biopsied and/or autopsied and had been examined at least once by MRI. In this series, contrary to what is regularly observed in toxoplasmic abscesses we did not find any lesion of the grey matter or any mass effect.

The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization.

By in situ hybridization analysis and immunoprecipitations following transfection of COS cells, we show that the Rev protein of the human immunodeficiency virus is necessary for envelope protein expression, which is correlated with the appearance in the cytoplasm of envelope-specific RNA. In the absence of cotransfection with a plasmid expressing Rev, envelope-specific RNA is retained in the nucleus. Several cis-acting sites in the envelope are involved, one of which is between nucleotides 7330 and 7735 and is required for the response to Rev.

HIV-associated endometritis.

Using immunohistochemical staining, in situ hybridization and a combination of both, we demonstrate here the replication of HIV in the endometrial stroma. Infected cells do not belong to the T-lymphocyte lineage but rather to a monocyte-macrophage cell type. This report suggests a possible relationship between HIV infection and endometritis.

HIV-2 in rhesus monkeys: serological, virological and clinical results.

Diseases induced by animal retroviruses are not considered to be good models for the human acquired immunodeficiency syndrome (AIDS) at present. The lack of an animal model for the human immunodeficiency virus (HIV) infection presents a main problem in the complete understanding of the pathogenesis of HIV-mediated diseases. Because of the homologies between simian immunodeficiency virus (SIV) and HIV-2, we inoculated rhesus monkeys with HIV-2 and HIV-2 adapted in vitro to monkey cells.