Biological Properties of Interferon‐α Produced <i>Ex Vivo</i> by Whole Blood of Patients Infected by Human Immunodeficiency Virus‐1

Chehadeh, Wassim; Hober, Didier; Chieux, Vincent; Alm, G.; Harvey, Jack; Lion, Georges; Mouton, Y; Wattré, P

doi:10.1046/j.1365-3083.1999.00552.x

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Consistent with these results, it was shown in a group of HIV-infected patients that only a minority of the patients had elevated IFN-␣ plasma levels, whereas almost all of the patients had increased Mx protein levels in their PBMC (108). In addition, the level of PBMC-associated Mx protein correlated with the disease stage of the patient (20,108). As we have shown for the monkeys in the present study, the rapid HIV progressors had higher Mx levels than slow progressors (108).…”

Section: Discussionsupporting

confidence: 81%

The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-α/β) and IFN-α/β-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection

Abel

Alegria-Hartman

Rothaeusler

et al. 2002

J Virol

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To define the role of alpha/beta interferons (IFN-α/β) in simian immunodeficiency virus (SIV) infection, IFN-α and IFN-β mRNA levels and mRNA levels of Mx, an antiviral effector molecule, were determined in lymphoid tissues of rhesus macaques infected with pathogenic SIV. IFN-α/β responses were induced during the acute phase and persisted in various lymphoid tissues throughout the chronic phase of infection. IFN-α/β responses were most consistent in tissues with high viral RNA levels; thus, IFN-α/β responses were not generally associated with effective control of SIV replication. IFN-α/β responses were differentially regulated in different lymphoid tissues and at different stages of infection. The most consistent IFN-α/β responses in acute and chronic SIV infection were observed in peripheral lymph nodes. In the spleen, only a transient increase in IFN-α/β mRNA levels during acute SIV infection was observed. Further, IFN-α and IFN-β mRNA levels showed a tissue-specific expression pattern during the chronic, but not the acute, phase of infection. In the acute phase of infection, SIV RNA levels in lymphoid tissues of rhesus macaques correlated with mRNA levels of both IFN-α and IFN-β, whereas during chronic SIV infection only increased IFN-α mRNA levels correlated with the level of virus replication in the same tissues. In lymphoid tissues of all SIV-infected monkeys, higher viral RNA levels were associated with increased Mx mRNA levels. We found no evidence that monkeys with increased Mx mRNA levels in lymphoid tissues had enhanced control of virus replication. In fact, Mx mRNA levels were associated with high viral RNA levels in lymphoid tissues of chronically infected animals.

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Section: Discussionsupporting

confidence: 81%

The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-α/β) and IFN-α/β-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection

Abel

Alegria-Hartman

Rothaeusler

et al. 2002

J Virol

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“…Extracted RNA was then dissolved in 50 mL of diethylpyrocarbonate (DEPC)-treated water (Sigma-Aldrich, Saint Quentin Fallavier, France) and used in the RT-PCR assays. Two positive extraction controls were used: the at Florida International University on May 26, 2015 http://jid.oxfordjournals.org/ Downloaded from first was used for IFN-a RNA detection and consisted of RNA extracted from whole blood cultivated as described elsewhere [20] and activated by Sendai virus (provided by Dr. D. Garcin, Department of Genetics and Microbiology, University of Geneva) for 5 h to induce IFN-a mRNA synthesis. The second positive control consisted of RNA extracted from Hep-2 cells (Biowhittaker) infected with CVB3 (ATCC) for 4 h and was used for EV RNA detection.…”

Section: Rna Extractionmentioning

confidence: 99%

Increased Level of Interferon‐α in Blood of Patients with Insulin‐Dependent Diabetes Mellitus: Relationship with Coxsackievirus B Infection

et al. 2000

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The activation of the interferon (IFN)-alpha system and its relationship with coxsackievirus B (CVB) infection has been analyzed in 56 patients with insulin-dependent diabetes mellitus (IDDM; 25 children and 31 adults). Elevated levels of IFN-alpha were found in plasma of 70% of patients (39/56), and a positive detection of IFN-alpha mRNA in blood cells by reverse transcriptase-polymerase chain reaction (RT-PCR) was observed in 75% of patients (42/56). Enterovirus (EV) RNA assayed by seminested RT-PCR was detected in the blood of 50% of IFN-alpha-positive patients but not in any IFN-alpha-negative patients. The results of genotype analysis of amplified EV RNA sequences (5 CVB2, 8 CVB3, and 8 CVB4) were concordant with the results of CVB-neutralization tests. The comparison between IFN-alpha, EV RNA, and serology suggested that the proportion of CVB infection associated with IFN-alpha positivity might be higher than is predicted from the investigation of EV RNA. Together, the results suggest that, in a majority of cases, a CVB infection is associated with clinical IDDM.

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“…The concentration of IFN-a in PBMCs culture supernatants was determined by a specific and sensitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), as described previously [Chehadeh et al, 1999[Chehadeh et al, , 2000b. The assay detection limit was 0.5 IU IFNa/ml.…”

Section: Immunoassay For Ifn-amentioning

confidence: 99%

A part of the VP4 capsid protein exhibited by coxsackievirus B4 E2 is the target of antibodies contained in plasma from patients with type 1 diabetes

Sauter

Chehadeh

Lobert

et al. 2008

Journal of Medical Virology

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The capsid protein VP4 was identified previously as the target of antibodies contained in plasma enhancing the coxscakievirus B4 (CV-B4) E2-induced production of IFN-alpha by peripheral blood mononuclear cells (PBMCs). The sequence of VP4 recognized by these antibodies was investigated. This sequence was identified as amino acids 11 to 30 by using synthetic overlapping peptides spanning VP4(CV-B4 E2) in competition experiments for antibodies enhancing the CV(B4 E2) induced production of IFN-alpha by PBMCs. This amino acid sequence was the major target of anti-VP4 antibodies according to enzyme-linked immunosorbent assays (ELISA). There was a positive correlation between the levels of anti-VP4 and anti-VP4(11-30) peptide antibodies detected by ELISA. The levels and the prevalences of these antibodies were significantly higher in patients with type 1 diabetes than in healthy controls. The proportions and the levels of those antibodies in patients were independent of HLA-DR alleles, age, or presence of ketosis in blood and were not associated with newly or previously diagnosed disease. The VP4(CV-B4 E2) amino acid sequence was submitted to the Swiss-model in project mode to visualize the possible shape of the sequence of VP4 corresponding to amino acids 11-30 which appeared to be constituted principally by an non-structured loop. In conclusion, the sequence of VP4 corresponding to amino acids 11-30, or a part of it plays a role in the plasma-dependent enhancement of CV-B4 E2-induced production of IFN-alpha by PBMCs, suggesting that at 37 degrees C the virus exhibits that region of VP4 to antibodies.

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Biological Properties of Interferon‐α Produced Ex Vivo by Whole Blood of Patients Infected by Human Immunodeficiency Virus‐1

Cited by 7 publications

References 29 publications

The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-α/β) and IFN-α/β-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection

The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-α/β) and IFN-α/β-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection

Increased Level of Interferon‐α in Blood of Patients with Insulin‐Dependent Diabetes Mellitus: Relationship with Coxsackievirus B Infection

A part of the VP4 capsid protein exhibited by coxsackievirus B4 E2 is the target of antibodies contained in plasma from patients with type 1 diabetes

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