Isolation of two H1N2 influenza viruses from swine in France

Summary Samples collected in 1987 and 1988 in Brittany from influenzainfected swine made it possible to isolate and antigenically characterize two H1N2 recombinant viruses (Sw/France/5027/87 and Sw/France/5550/88). The former virus was cloned and reinoculated to swine to allow reproduction of the disease and reisolation of a strain similar to the original one. The serodiagnostic tests carried out on both the original sera and those from the experimentally infected animals confirmed that the virus was actually type Sw/H1N2.     

Interaction between cytochrome b5 and hemoglobin: involvement of beta 66 (E10) and beta 95 (FG2) lysyl residues of hemoglobin.

In erythrocytes the reduction of oxidized hemoglobin (methemoglobin) is dependent upon an electron transport reaction between cytochrome b5 and methemoglobin. These two proteins are believed to form a complex whose bonding is principally determined by complementary charge interactions between acidic groups of cytochrome b5 and basic groups of hemoglobin. In order to refine this model, three surface lysyl hemoglobin variants--namely Hb N Baltimore beta 95 (FG2) Lys leads to Glu, Hb I Toulouse beta 66 (E10) Lys leads to Glu, and Hb I Philadelphia alpha 16 (A14) Lys leads to Glu--have been studied with respect to their reducibility and ability to bind cytochrome b5. In the two former variants, the substituted amino acids are located near the heme crevice; in the third one the substitution lies far from it. Substitutions of lysine for glutamic acid in positions beta 66 and beta 95 perturb the formation of the cytochrome b5--hemoglobin complex and result in a dramatic impairment of the cytochrome b5-mediated reduction, whereas the same mutation in position alpha 16 has no effect. We conclude that the lysine residues in positions beta 66 and beta 95 are directly involved in the binding of cytochrome b5. The three-dimensional structure of hemoglobin suggests that the cytochrome b5-binding domain of hemoglobin is constituted by four lysine residues surrounding the heme crevice in both alpha and beta chains. Similarities with other interacting hemoproteins are discussed.     

Stimulation of both humoral and cellular immune responses to HIV-1 gp120 by interleukin-12 in Rhesus macaques

The adjuvant effect of recombinant Rhesus macaque interleukin-12 (RhIL-12) on the induction of cellular and humoral immune responses elicited by the HIV-1 subunit vaccine protein gp120 in Rhesus macaques was examined. RhIL-12 in conjunction with gp120 was given at day 0, 28 and 84 intramuscularly. Coadministration resulted in an approximate 10-fold increase in plasma anti-gp120 antibody levels as compared to levels generated in control monkeys receiving gp120 alone. Potentiation of the humoral arm of the immune response was evident by both ELISA and an antiviral bioassay. In addition, RhIL-12 was found to produce a significant increase in gp120-specific proliferative responses and in the frequency of antigen-specific IFN-gamma and IL-2 producing T cells after restimulation of PBMC with gp120 in vitro indicating that RhIL-12 potentiates cell-mediated immune responses as well. A critical finding was that during the course of the study, RhIL-12 did not induce a neutralizing antibody response to the administered cytokine. The doses of RhIL-12 were well tolerated and no detectable adverse side-effects on hematopoietic and hepatic parameters were noted. The data revealed that IL-12, when coadministered intramuscularly, acts as a potent adjuvant which is able to enhance not only cellular but also humoral immune responses to gp120 in non-human primates and may have to be considered in future HIV vaccine strategies.     

West Nile virus, Guadeloupe

To determine whether West Nile virus (WNV) had reached the archipelago of Guadeloupe, a serologic study in horses and birds was conducted in 2002. Immunoglobulin (Ig) G, IgM, enzyme-linked immunosorbent assay, and seroneutralization tests identified WNV infection in horses and chickens. Six months later, a high rate of seroconversion was observed in horses.     

Infectious complications in sickle cell disease are influenced by HLA class II alleles

Despite systematic antibiotic therapy, severe infections (septicemia, meningitis, or osteomyelitis) are a major cause of mortality and morbidity in children with sickle cell disease (SCD). In this study, we explored the possibility that polymorphism at the human leukocyte antigen (HLA) locus might constitute an immunogenetic modifying factor to the intrinsic susceptibility to infection in patients with SCD. A cohort of 80 SCD patients living in Paris, 43 with at least one major infectious complication and 37 without infections, were typed for HLA class II loci by polymerase chain reaction-sequence-specific primers (PCR-SSP). We found that significantly more patients without infections carry the HLA class II DRB1*15 specificity than did patients with infections (21.6% in the first group, versus 4.7% in the second group; chi(2) = 10.47, p(c) = 0.01), supporting a protective effect of this allele. Conversely, significantly more patients were found to carry the DQB1*03 specificity within the group of severe infections, supporting a negative effect (34.9% versus 12.2%, chi(2) = 9.41, p(c) = 0.01). These findings suggest a direct involvement of HLA polymorphism in the development of major infections in SCD. Together with previous data on polymorphism of the Fc receptor and of the mannose-binding lectin, they provide evidence for a polygenic immunomodulation of the constitutively increased infectious risk in SCD.     

Impairment of the Growth of Plasmodium Falciparum in HbEE Erythrocytes

HbE is a β-chain mutant frequently found among inhabitants of Southeast Asia and surrounding territories. We find that Plasmodium falciparum multiplies more slowly in erythrocytes from individuals homozygous for HbE than in cells from HbA individuals. In contrast, this parasite grows normally in erythrocytes heterozygous for HbE. This is the first direct evidence that suggests what has been suspected on the basis of circumstantial data, that HbE-containing erythrocytes might be advantageous to the carrier in regions with endemic malaria.     

Quantitation of hemoglobin A1c: a rapid, automated precision-chromatography technique.

Hemoglobin A1c is increased in patients with diabetes mellitus and its level reflects the status of blood glucose equilibrium over a period of several weeks. The practical use of its estimation was hampered by technical difficulties in investigating large series of samples. In order to apply this examination for routine purposes we describe in this paper acceleration and full automatization of the original chromatographic method allowing quantitation of hemoglobin A1c in 45 min.     

Molecular Heterogeneity of β-Thalassemia in Algeria: How to Face Up to a Major Health Problem

This study concerns the molecular characterization of β-thalassemia (β-thal) alleles in 210 chromosomes. In the studied population, mutations were detected in 98% of the β-thalassemic chromosomes. Twenty-one molecular defects have been found, where the five dominant mutations, IVS-I-110 (G>A), nonsense mutation at codon 39 (C>T), the frameshift codon (FSC) 6 (?A), IVS-I-1 (G>A), and IVS-I-6 (T>C), account for 80% of the independent chromosomes. Among the remaining alleles, 16 different mutations were identified, half of them being described for the first time in Algeria. These include the ?101 (C>T) and the ?90 (C>T) mutations in the distal and proximal promoter elements, respectively, the FSC 8 (?AA), IVS-I-5 (G>T), IVS-I-128 (T>G), FSC 47 (+A), IVS-II-1 (G>A), and the substitution in the polyadenylation signal (poly A) site AATAAA>AATGAA. Haplotype analyses on rare variants were performed. The possible origin of these mutations either by founder effect or by migrations is discussed, and raises the question of an adequate strategy to be used adapted to socio-economical status.