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A Chéret

Publications and source records attributed to A Chéret.

11 recordsLinked to original sources
PubMed2001

Longitudinal analysis of CD8(+) T-cell phenotype and IL-7, IL-15 and IL-16 mRNA expression in different tissues during primary simian immunodeficiency virus infection.

Infection of macaques with pathogenic isolates of simian immunodeficiency virus (SIV) represents a useful model of HIV infection that offers the unique opportunity to investigate the very early modifications that affect CD8(+) T-lymphocyte subsets and related cytokines during lentiviral infection. Herein, three cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac 251. In fresh isolated mononuclear cells from blood, lymph node and bronchoalveolar lavage, we analyzed changes in the phenotype of CD8(+) T cells and we used reverse transcription-PCR to monitor the expression of IL-7, IL-15 and IL-16 mRNA. We demonstrated that an expansion of CD8(+)CD28(-) T cells occurs from the third week of infection on in the peripheral blood and in the lung, whereas CD8(+)CD28(+) T cells expand in the lymph nodes. Concomitantly, we evidenced mRNA modulations in IL-16, IL-15 and IL-7 expression in the three compartments studied. The containment of systemic viral replication was associated with an overexpression of IL-16 mRNA in the lung and in the peripheral blood. Given the immunomodulatory properties of IL-15 and IL-7 and the potential antiviral ability of IL-16, these perturbations could have important implications in early viral dissemination and HIV immunopathogenesis.

Animals↗
PubMed1999

RANTES, IFN-gamma, CCR1, and CCR5 mRNA expression in peripheral blood, lymph node, and bronchoalveolar lavage mononuclear cells during primary simian immunodeficiency virus infection of macaques.

Primary infection of macaques with pathogenic isolates of simian immunodeficiency virus (SIV) (as a model of HIV infection in humans) represents a unique opportunity to study early lentivirus/host interactions. We sought to determine whether there is a temporal relationship linking SIV replication and dissemination and the expression of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) and the SIV/HIV coreceptor CCR5 in different tissues during acute SIV infection of macaques. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate of SIVmac251. RT-PCR was used to monitor the expression of RANTES and CCR5 mRNA in fresh isolated mononuclear cells from blood, lymph node, and bronchoalveolar lavages. These expressions were compared to those of IFN-gamma as an indicator of the development of the immune response and to another receptor for RANTES, CCR1, which is not described as a coreceptor for SIV/HIV-1 entry. An enhancement of CCR1/CCR5 mRNA expression was noticed during primary SIVmac251 infection of macaques, mainly in tissue. In the three different compartments investigated, IFN-gamma and RANTES overexpression was noticed by the time of systemic viral replication containment. Our results put CCR5 and RANTES mRNA expression back in the context of inflammatory and immune responses to SIV primary infection.

Animals↗
PubMed1998

Selective quasispecies transmission after systemic or mucosal exposure of macaques to simian immunodeficiency virus.

Sexual transmission is the major cause of the AIDS epidemic. For the development of new antiviral and vaccine strategies, we therefore need to understand the mechanisms by which lentiviruses cross the mucosal barrier and the subsequent pathogenic consequences. For this purpose, experimental approaches are greatly facilitated by the development of relevant animal models. In this study, macaques were inoculated intravenously, intrarectally, or intravaginally with a pathogenic cell-free isolate of SIVmac251. Patterns of virological and immunological events significantly differed between vaginally (transient viremia, late seroconversion) and intravenously or intrarectally inoculated monkeys (persistent viremia and early seroconversion). Two weeks after infection, analysis of the env gene nucleotide sequences of proviruses recovered from PBMCs demonstrated that most of the differences were observed in the V1 loop. Three viral variants were specifically associated with vaginal transmission, whereas no such selection was evidenced after intravenous or intrarectal transmissions. These results are in favor of specific mechanisms associated with vaginal transmission, implicating viral envelope structure.

Amino Acid Sequence↗
PubMed1996

Cytokine mRNA expression in mononuclear cells from different tissues during acute SIVmac251 infection of macaques.

We used semiquantitative RT-PCR to monitor the expression of mRNA encoding cytokines (IL-1 beta, IL-6, TNF-alpha, and IL-10) and IFN-gamma in fresh isolated peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs), and mononuclear cells obtained after bronchoalveolar lavages (BALMCs), of four cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian immunodeficiency virus (SIVmac251). To investigate the effects of the viral load on the expression of the cytokines, two monkeys received 30 mg kg-1 day-1 of didanosine (ddI). The two nontreated monkeys became infected and seroconverted, whereas the ddI-treated monkeys were completely protected as demonstrated by all criteria of diagnosis of SIV infection. Concomitant with the peak of viral replication (2 weeks after the experimental inoculation), high levels of IL-6 mRNA were produced in PBMCs, LNMCs, and BALMCs of the two placebotreated infected monkeys. Overexpression of TNF-alpha and IL-10 mRNAs was sometimes observed in LNMCs and BALMCs. A progressive overexpression of IFN-gamma mRNA, starting 2 weeks after experimental inoculation, was observed in BALMCs from infected animals. Concurrently, a marked increase in the CD8+ lymphocyte percentage in the BAL fluids was detected by FACS analysis. Thus, our results emphasize the importance of a comparative study of the expression of cytokines in different tissues. They suggest the interactions of monocyte/macrophage monokine production with viral replication, as well as the role of IFN-gamma in the development of lung cellular immunity to SIV infection.

Acute Disease↗
PubMed1996

Superinfection of HIV-2-preinfected macaques after rectal exposure to a primary isolate of SIVmac251.

To test the protection afforded by a weakly pathogenic HIV-2 isolate against the superinfection or development of SIV-induced disease, we intrarectally challenged six HIV-2-preinfected rhesus monkeys with a pathogenic isolate of SIVmac251. At the time of SIV challenge, none of these HIV-2-infected animals was positive for virus isolation, p27-Gag antigenemia, or HIV-2 provirus detection in PBMCs or peripheral lymph nodes. However, all monkeys exhibited anti-HIV-2 antibody titers ranging from 10(2) to 10(3). Neutralizing antibodies against the challenge SIV strain were also detected in two animals. After rectal exposure to SIVmac251, five of the six HIV-2-preinfected macaques were superinfected. SIVmac251 DNA sequences were detected repeatedly in the PBMCs of the five superinfected animals and the two controls, whereas no HIV-2 provirus was detected for 14 months postchallenge. The one monkey that resisted superinfection was negative for all SIV infection criteria. This monkey exhibited the highest anti-SIV ELISA and cross-neutralizing antibody titers on the day of SIV challenge. Preinfection with a weakly pathogenic HIV-2 ROD isolate protected one of six macaques from infection with the closely related pathogenic SIVmac251 isolate, but no protection from the progression of disease was evidenced in the other five.

AIDS Vaccines↗
PubMedDate not supplied

[Tocolysis with nifedipine: its use in current practice].

OBJECTIVES: To assess tocolysis with nifedipine in preterm labour during actual clinical practice in terms of efficacy and safety. PATIENTS AND METHODS: Retrospective observational study during two years including preterm labour between 26 and 33+6 weeks of amenorrhea. Preterm labour was defined by the presence of three or more uterine contractions in 10 minutes associated to cervical modifications diagnosed by vaginal sonography (length<or=25 mm). Patients were excluded if they had more than two fetuses or other gestational pathologies. Tocolysis resulted in oral taking of 30 mg of nifedipine (3x10 mg) with continuous follow-up of blood pressure. Tocolysis was modified when contractions did not disappear. Success was defined when delivery was delayed more than 48 hours. Failure was defined either by a delivery occurring in the first two days of tocolysis or when a modification of treatment was required. RESULTS: Fifty-eight patients were included, 10 of whom having a twin pregnancy. Success was obtained in 84% of patients (49/58). All of these women did not deliver during the first seven days after introduction of tocolysis. Five patients delivered in the first two days after tocolysis and four others required a change in tocolysis. Mean gestational age at delivery was 37+5 weeks and 35 weeks for single and twin pregnancies, respectively. No maternal or fetal side effects were described. DISCUSSION AND CONCLUSION: Nifedipine could be prescribed for tocolysis in actual clinical practice because it seems to have safety and excellent tolerance.

Adolescent↗
PubMedDate not supplied

Variation in virological parameters and antibody responses in macaques after atraumatic vaginal exposure to a pathogenic primary isolate of SIVmac251.

We developed an animal model for the male-to-female transmission of human immunodeficiency virus, consisting of an atraumatic vaginal application of simian immunodeficiency virus onto the intact vaginal mucosa of cynomolgus macaques. Different doses of a pathogenic isolate of SIVmac251, with or without seminal plasma, were infused into the vaginas of female macaques. Infection of macaques could be achieved after a single exposure to the virus. Two patterns of infection were underscored with no relation to the virus dose inoculated: in 50% of the monkeys, SIV was persistently recovered and a strong antibody response to SIV was evidenced in blood and vaginal secretions. In the other infected animals, SIV infection was only transiently evidenced and a weak systemic antibody response was detected. It appeared that the presence of seminal plasma may be implicated in this variability only when low doses of virus are inoculated. Sequence analysis of the env gene of SIV revealed that most of the persistently viraemic animals were infected with a viral variant different from that of transiently viraemic macaques.

Amino Acid Sequence↗
PubMedDate not supplied

Nitric oxide synthesis during acute SIV mac251 infection of macaques.

During HIV1 infection, nitric oxide (NO) could significantly contribute to immune dysregulation by its multiple effects on the modulation of the host immune response. The in vivo regulation of NO production is attributable to several nitric oxide synthases, one of which is a cytokine-inducible enzyme (iNOS). In vitro experiments suggest that iNOS expression in macrophages may be directly modulated by HIV infection. Acute infection of macaques with a pathogenic strain of the simian immunodeficiency virus (SIV) represents a relevant animal model for the in vivo study of the relationships between iNOS expression and lentiviral replication. Indeed, acute infection in this model is characterized by high rates of viral replication associated with early cytokine dysregulations, in the absence of opportunistic infection. In our experiment, two cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac251, and iNOS gene expression was investigated ex vivo during acute infection in mononuclear cells obtained from bronchoalveolar lavage (BALMCs). An enhancement of this gene expression was observed as early as the second week of infection, at the time of peak of systemic viraemia, and increased until day 31 p.i. This overexpression was concomitant with a marked linear increase in IFN gamma expression in BALMCs. At the time of systemic viral load peak, the production of NO in plasma of these two monkeys was evidenced by the detection of large amounts of nitrate.

Acute Disease↗
PubMedDate not supplied

Consequences of ddI-induced reduction of acute SIVmac251 virus load on cytokine profiles in cynomolgus macaques.

This study evaluates the consequences of antiretroviral treatment of the acute simian immunodeficiency virus (SIV) primary infection on virus load and cytokine responses. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate (SIVmac251). Animals were pretreated with 10.8 mg/kg/day of dideoxyinosine (ddI) from 4 days before inoculation, and treatment was continued for 28 days. Proinflammatory (IL6, IL1 beta and TNF alpha) and antiinflammatory (IL10) cytokine and lymphokine (IL2, IL4 and IFN gamma) polymerase chain reaction (PCR) ratios were monitored in unmanipulated peripheral blood mononuclear cells (PBMCs) during acute infection by using a semiquantitative reverse transcription (RT)-PCR method. PBMC-associated virus loads were dramatically reduced compared to those of placebo-treated macaques. Nevertheless, a transient rise in IL6, IL1 beta, TNF alpha and IL10 mRNA expression was observed in PBMCs. IL2, IL4 and IFN gamma mRNAs were either undetectable or weakly detectable throughout the study, with no major changes. Despite a dramatic reduction in the acute viral loads in ddI-treated monkeys, early cytokine mRNA profiles were comparable to those of untreated SIVmac251-infected monkeys. Contrary to what was previously evidenced during primary infection with an attenuated SIV clone, no increase in IL2 and IL4 mRNA was detected in PBMCs of the ddI-treated monkeys, although these monkeys exhibited virus loads similar to those evidenced in macaques infected by attenuated SIV. These data indicate that differential lymphokine expression patterns found in pathogenic and Nef-truncated SIV-infected monkeys may not be strictly dependent on virus load levels.

Acute Disease↗
PubMedDate not supplied

Chemoattractant factors (IP-10, MIP-1alpha, IL-16) mRNA expression in mononuclear cells from different tissues during acute SIVmac251 infection of macaques.

We have used semiquantitative RT-PCR to monitor the expression of mRNA encoding chemoattractant factors IP-10, MIP-1alpha, and IL-16 in freshly isolated peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs), and mononuclear cells obtained after bronchoalveolar lavages (BALMCs) of two cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian immunodeficiency virus, SIVmac251. Concomitant with the peak of systemic viral replication (two weeks after experimental inoculation) and proinflammatory cytokine IL-6 mRNA expression, high levels of MIP-1alpha and IP-10 mRNA were produced in LNMCs and BALMCs. In BALMCs, in which we have reported a marked progressive overexpression of IFN-gamma mRNA coinciding with an increase in the CD8+ lymphocyte percentages, we noticed a progressive overexpression of IL-16 mRNA. Our results suggest the role of chemokines IP-10, MIP-1alpha, and IL-16 in the development of inflammatory and immune responses during the early stages of lentiviral infection.

Animals↗