Search PubMed⌕ Search

Biomedical subjects

R Cantin

Publications and source records attributed to R Cantin.

15 recordsLinked to original sources
PubMed2000

Interaction between virion-bound host intercellular adhesion molecule-1 and the high-affinity state of lymphocyte function-associated antigen-1 on target cells renders R5 and X4 isolates of human immunodeficiency virus type 1 more refractory to neutralization.

The oligomeric nature of the viral envelope proteins has been partly held responsible for the observed differences in neutralization sensitivity between primary and laboratory-adapted strains of human immunodeficiency virus type 1 (HIV-1). However, recent evidence suggests that host factors can also modify the sensitivity of HIV-1 particles to neutralization. Having previously demonstrated that the acquisition of host-encoded intercellular adhesion molecule (ICAM)-1 proteins by newly formed viruses has a functional significance for the life cycle of HIV-1, we investigated whether the acquisition of host-derived ICAM-1 by HIV-1 could affect the virus sensitivity to neutralization. In this study, we have first shown that the physical presence of host cell membrane ICAM-1 on HIV-1 was not modifying virus sensitivity to neutralization by either two different anti-gp120 monoclonal antibodies (0.5beta and 4.8D) or soluble CD4. However, the ability of the F105 anti-gp120 monoclonal antibody (specific for the CD4-binding site) to neutralize ICAM-1-bearing virions was diminished when target cells were pretreated with an lymphocyte function-associated antigen-1 (LFA-1)-activating antibody. Interestingly, ICAM-1/POS progeny viruses were found to be slightly more resistant to neutralization by individual human sera in target cells expressing a low-affinity form of LFA-1 than viruses devoid of host-encoded ICAM-1 proteins. This resistance was markedly enhanced when target cells expressed an activated LFA-1 form on their surface. These results suggest that the interaction between virally embedded host ICAM-1 and target cell surface LFA-1 should be considered a factor modulating neutralization sensitivity of HIV-1 by human sera from HIV-1-infected individuals.

Adult↗
PubMed1998

T cells expressing activated LFA-1 are more susceptible to infection with human immunodeficiency virus type 1 particles bearing host-encoded ICAM-1.

The incorporation of host-derived proteins in nascent human immunodeficiency virus type 1 (HIV-1) particles is a well-established phenomenon. We recently demonstrated that the physical presence of host-encoded ICAM-1 glycoproteins on HIV-1 leads to a significant increase in virus infectivity in an ICAM-1/LFA-1-dependent fashion (J.-F. Fortin, R. Cantin, G. Lamontagne, and M. Tremblay, J. Virol. 71:3588-3596, 1997). We show here that conversion of LFA-1 to high affinity for ICAM-1 with the use of anti-LFA-1 antibodies (clones NKI-L16 and MEM83) markedly enhances the susceptibility of different target T-lymphoid cell lines, as well as of primary peripheral blood mononuclear cells, to infection by ICAM-1-bearing HIV-1 particles (6- to 95-fold). It is known that T-cell receptor (TCR) cross-linking induces a transient increase in LFA-1 affinity for ICAM-1. Treatment of peripheral blood mononuclear cells with anti-TCR antibodies (clone OKT3) resulted in a transient increase in susceptibility to infection by ICAM-1-positive virions that parallels the previously reported kinetics of the LFA-1/ICAM-1 adhesion mechanism. Our results led us to postulate that the strong interaction taking place between virally incorporated ICAM-1 and cell surface-activated LFA-1 markedly enhances the efficiency of virus binding and entry, thus favoring greater infection by ICAM-1-bearing HIV-1 particles. In view of the knowledge that primary HIV-1 isolates harbor host-derived ICAM-1 on their surfaces, these results provide new information about the role of host-derived ICAM-1 in the life cycle of HIV-1 and how it could positively modulate the dynamics of the viral infection, mainly in cellular compartments, such as the lymphoid tissues, where the level of cellular activation is high and where the probability of encountering a T cell expressing the activated LFA-1 form is also elevated.

Antibodies↗
PubMed1997

The acquisition of host-derived major histocompatibility complex class II glycoproteins by human immunodeficiency virus type 1 accelerates the process of virus entry and infection in human T-lymphoid cells.

Infection by human immunodeficiency virus type 1 (HIV-1) results in a progressive depletion of CD4+ T lymphocytes, leading to fatal immunodeficiency. The mechanisms causing the marked loss of CD4+ T lymphocytes are incompletely understood. However, several lines of evidence indicate that direct cytopathology mediated by HIV-1 is a key element in such CD4+ T-cell depletion. In this study, we investigated whether the previously reported incorporation of host-derived major histocompatibility class II glycoproteins (MHC-II) on HIV-1 can alter its replicative capacity. To achieve this goal, virus stocks were produced in parental MHC-II-expressing RAJI cells and in MHC-II-negative RAJI mutants (RM3), both of which have been stably transfected with human CD4 cDNA to allow productive infection with HIV-1. An enhancement of the rate/efficiency of virus entry was seen after infection with normalized amounts of virions carrying host-derived MHC-II on their surface as compared with inoculation with virions devoid of cellular MHC-II. Data from time-course and infectivity experiments showed that the kinetics of infection were more rapid for virions bearing host-derived MHC-II glycoproteins than for MHC-II-free HIV-1 particles. These results suggest that virally embedded cellular MHC-II glycoproteins are functional and can have a positive effect on early events in the virus replicative cycle. Therefore, we show that the acquisition of cellular MHC-II glycoproteins by HIV-1 can modify its biologic properties and might, consequently, influence the pathogenesis of this retroviral disease.

B-Lymphocytes↗
PubMed1997

The presence of host-derived HLA-DR1 on human immunodeficiency virus type 1 increases viral infectivity.

Human immunodeficiency virus type 1 (HIV-1) incorporates several host cell components when budding out of the infected cell. One of the most abundant host-derived molecules acquired by HIV-1 is the HLA-DR determinant of the major histocompatibility complex class II (MHC-II) molecules. The fact that CD4 is the natural ligand of MHC-II prompted us to determine if such virally embedded cellular components can affect the biology of the virus. Herein, we report for the first time that the incorporation of cellular HLA-DR1 within HIV-1 enhances its infectivity. This observation was made possible with virions bearing or not bearing on their surfaces host-derived HLA-DR1 glycoproteins. Such virus stocks were prepared by a transient-expression system based on transfection of 293T cells with a recombinant luciferase-encoding HIV-1 molecular clone along with plasmids encoding the alpha and beta chains of HLA-DR1. Cell-free virions recovered from transfected cells were shown to have efficiently incorporated host-derived HLA-DR1 glycoproteins. Infectivity was increased by a factor of 1.6 to 2.3 for virions bearing on their surfaces host-derived HLA-DR1. The observed enhancement of HIV-1 infectivity was independent of the virus stocks used and was seen in several T-lymphoid cell lines, in a premonocytoid cell line, and in primary peripheral blood mononuclear cells. Finally, we determined that the presence of virion-bound cellular HLA-DR1 is associated with faster kinetics of virus infection. Taken together, these results suggest that HLA-DR-1-bearing HIV-1 particles had a greater infectivity per picogram of viral p24 protein than HLA-DR1-free virions.

Cell Line↗
PubMed1997

Host-derived ICAM-1 glycoproteins incorporated on human immunodeficiency virus type 1 are biologically active and enhance viral infectivity.

Human immunodeficiency virus type 1 (HIV-1) acquires several host cell membrane proteins when it buds from infected cells. To study the effect of virally incorporated host-derived ICAM-1 glycoproteins on the biology of HIV-1, we have developed a transient expression system that has enabled us to produce virus particles differing only in the absence or the presence of virion-bound ICAM-1. By using a single-round infection assay based on an ICAM-1-negative target T-cell line stably transfected with an HIV-1 long terminal repeat driven luciferase gene construct, we have been able to demonstrate that the acquisition of host-derived ICAM-1 by HIV-1 has functional significance, since it leads to a pronounced increase in viral infectivity (4.6- to 9.8-fold) in an ICAM-1/LFA-1-dependent fashion, as shown by blocking with anti-ICAM-1 and -LFA-1 antibodies. The same potentiating effect on viral infectivity was also observed with monocytoid cells. Studies of the kinetics of infection revealed that the positive effect mediated by virally embedded host cell membrane ICAM-1 is due to an increase in the efficiency of early steps in the viral life cycle. These results provide new insights into how incorporation of host proteins can modulate the biological properties of HIV-1. Our findings have direct clinical relevance, considering that ICAM-1 is expressed on the surface of virus-infected cells and, more importantly, that host-derived ICAM-1 has been shown to be acquired by clinical HIV-1 isolates grown on primary mononuclear cells. These data justify a more complete analysis of the other putative role(s) that virally incorporated ICAM-1 may play in the life cycle of HIV-1, for example, at the level of neutralization sensitivity.

Cell Line↗
PubMed1996

The amount of host HLA-DR proteins acquired by HIV-1 is virus strain- and cell type-specific.

We semiquantitatively monitored the incorporation of host membrane proteins on different strains of human immunodeficiency virus type 1 (HIV-1) grown in several human CD4+ lymphoid cell lines and in primary mitogen-stimulated peripheral blood mononuclear cells. The relative amounts of virally acquired cell proteins were estimated by the ability of HIV-1 to be captured by magnetic beads coated with monoclonal antibodies. Here we report that, among host surface proteins studied, HLA-DR molecules were the most abundant virion-bound host molecules. We have also found that, in contrast to previous studies, HLA-DP and -DQ isotypes were also present on virus progeny. More importantly, we determined that the relative levels of virally acquired host HLA-DR proteins, as estimated by capture with immunomagnetic beads, greatly differed depending on the virus strain and the producer cell. These observations extend beyond already published results and suggest that the process of incorporation of cellular molecules on newly released virus particles is a phenomenon that relies on both the virus strain and producer cell line. These in vitro observations are of prime importance considering that virus-acquired host molecules have been recently shown to affect the biology of HIV.

Antibodies, Monoclonal↗
PubMed1996

Repression of human immunodeficiency virus type 1 long terminal repeat-driven gene expression by binding of the virus to its primary cellular receptor, the CD4 molecule.

We have previously postulated that the binding of the human immunodeficiency virus type 1 (HIV-1) to cell surface CD4 induces signal transduction pathways that down-modulate production of progeny virions in acutely infected T cells (M. Tremblay, S. Meloche, S. Gratton, M. A. Wainberg, and R.-P. Sékaly, EMBO J. 13:774-783, 1994). To evaluate the possibility that CD4 cross-linking might indeed affect viral gene expression, we have introduced a molecular construct made of the luciferase reporter gene placed under the control of the regulatory elements of HIV-1 in several CD4-positive T-cell lines. We found that cross-linking of CD4 with defective HIV-1 particles and heat-inactivated viruses inhibits long terminal repeat-dependent luciferase expression. Experiments revealed that the gp120-CD4 interaction was necessary to repress HIV-1 long terminal repeat-dependent luciferase activity. The cytoplasmic domain of CD4 was also found to be required for this effect to occur. The virus-mediated signal transduction was shown to be mediated via p56lck-dependent and -independent pathways. These results indicate that the earliest event in the HIV-1 replicative cycle, namely, the binding of the virus to its cellular receptor, can lead to signal transduction culminating in down-modulation of viral gene expression. Thus we propose that defective viruses could regulate the pathogenesis of HIV disease as they constitute the vast majority of circulating HIV-1 particles.

CD4 Antigens↗
PubMed1989

[Acute organic psychoses in the general hospital. II. Treatment and development].

This paper outlines the importance of close collaboration between the consultant psychiatrist and the non-psychiatric team. The aetiological treatment requires the competence of the physician, while the management of behavioral disturbances may require the intervention of the psychiatrist. The latter may be helpful in the choice of the right psychotropic medication and/or in counselling the team regarding the attitudes to be held towards the patient. Furthermore, the course of acute organic psychotic disorders is described.

Acute Disease↗
PubMed1989

[Acute organic psychoses in the hospital. I. Clinical and differential diagnosis].

In the general hospital, some patients may exhibit major mental disturbances secondary to a physical disorder. Early diagnosis of the organic etiology of these psychiatric disorders is essential, since the sooner an etiological treatment is applied, the better is the prognosis. In most cases, these psychiatric organic disorders should be treated in the general hospital. The article intends to make the non-psychiatric physician more familiar with the diagnosis of acute psychoses, especially in helping him to distinguish the organic from the 'functional' psychoses.

Acute Disease↗
PubMed1988

Intimal hyperplasia and thrombosis of the visceral arteries in a young woman: possible relation with oral contraceptives and smoking.

This is a report of a 26-year-old woman who died of a massive intestinal infarction caused by occlusion of the celiac axis and the superior and inferior mesenteric arteries. Autopsy showed intimal hyperplasia and an overlying thrombus that obstructed the lumen of the vessel. As shown by Irey et al., exogenous or endogenous female reproductive steroids can act on the vascular system as a target organ and induce intimal hyperplasia and thrombus formation. The effects of contraceptive estrogens and progestogens are discussed, but the catalytic effect of heavy cigarette smoking appears to be the factor that induces, in predisposed women with hyperplasia, thrombosis of visceral arteries. In this case report we want to emphasize that the association between smoking and oral contraceptives can cause cardiovascular disease in young women. Failure to recognize this fact could result in delayed diagnosis and worsen the prognosis.

Adult↗
PubMed1982

Desmoplastic diffuse mesothelioma.

Twenty-seven cases of desmoplastic diffuse malignant mesothelioma (26 pleural, one peritoneal) are described. In 19 cases the tumor cell type was sarcomatous and in six others it was biphasic (malignant elements of both epithelial and mesenchymal aspect). There were only two cases where the tumor cell type was purely epithelial. The clinical course was often rapid; the mean survival period in 11 cases of purely sarcomatous type was 6.18 months. Only one case of purely sarcomatous type lived for more than 1 year as opposed to four of eight cases with an epithelial component. Metastases occurred more frequently in desmoplastic (60.1%) than in nondesmoplastic diffuse mesothelioma (42.5%). The tumor cell type (epithelial, mesenchymal) accompanying desmoplastic mesotheliomas and not the extent of desmoplasia determines their behavior. Desmoplasia in diffuse mesotheliomas is often the result of tumor cells assuming the functional capacity of fibroblasts and has frequently been confused with reactive fibrosis. Cytologic abnormalities, tissue infiltration, and foci of necrosis indicate the neoplastic nature of the process in most instances.

Adult↗
PubMedDate not supplied

Management of dental caries as an infectious disease.

Dental caries is an infectious disease that demineralizes tooth structure as a consequence of bacterial metabolism. Chemical suppression of bacteria, especially using stannous fluoride, is gaining popularity because of its practicality and clinical efficacy.

Child, Preschool↗