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1.
Preprint in English | bioRxiv | ID: ppbiorxiv-197343

ABSTRACT

Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-, interferon-{lambda}1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.

2.
Presse Med ; 34(10 Suppl): 1S8-13, 2005 Jun 04.
Article in French | MEDLINE | ID: mdl-16025661

ABSTRACT

OBJECTIVE: To evaluate clinical and laboratory results in HIV-infected patients with complete viral suppression under HAART (highly active antiretroviral treatment) for whom treatment was interrupted and to identify risk factors associated with prolonged (i.e., successful) treatment interruption. METHODS: Retrospective study of patients who interrupted therapy while on HAART with a plasma HIV RNA <400 copies/mL. Multivariate regression analysis was performed to identify factors associated with a prolonged interruption (more than 6 months). RESULTS: 36 treatment interruptions in 30 patients were analyzed. Patients' mean age was 42 years, 83% were men, and 60% were infected through homosexual contact. Median CD4 cell count at initiation of HAART was 292/mm3 and median viral load 43,000 copies/mL. Reported reasons for HAART discontinuation included patient or clinician choice (n=21) or drug toxicity (n=15). Median CD4 cell count when treatment interruption began was 606/mm3, and its median duration was 14 months. During treatment interruption, adverse clinical events or laboratory findings occurred in 9 patients (30%), all of whom had a CD4 cell count nadir < 300/mm3. When HAART resumed, median CD4 cell count was 302/mm3, and median viral load 59,800 copies/mL. Plasma HIV RNA dropped to <400 copies/mL in all patients within 4 months of resuming treatment. In multivariate analysis, the factors associated with resuming HAART within 6 month of treatment interruption were: HAART including non-nucleoside analog (adjusted Hazard Ratio [aHR]: 3.6, 95% CI: 1.2-10.6, p = 0.02), a CD4 cell count nadir < 300 (adjusted Hazard Ratio [aHR]: 5.5, 95% CI: 2.0-26, p = 0.0057), undetectable plasma HIV RNA for longer than 21 months at the interruption (aHR: 7.2, 95% CI: 2-26, p = 0.002). This probability was 45.5% in patients with a CD4 cell count nadir < 300 and 14.3% in the others (p 0.10). CONCLUSION: Antiretroviral treatment should be interrupted only with caution in patients with a CD4 cell count nadir <300/mm3 because of the risk of adverse clinical events or laboratory findings.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Adult , CD4 Lymphocyte Count , Female , HIV Reverse Transcriptase/antagonists & inhibitors , Humans , Male , Multivariate Analysis , RNA, Viral/blood , Retrospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load
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