RESUMEN
Emerging infectious diseases appear recurrently and represent a threat to global health security. Africa is particularly exposed to the risks of infectious epidemics, due to both the number of circulating infectious agents, especially in wildlife, and the social and environmental factors that promote their epidemic spread. Ebola outbreaks in West Africa in 2014 and those in the DRC that began in 2018 were an opportunity to develop and deploy new diagnostic techniques in laboratories in Guinea and the Democratic Republic of the Congo (DRC). These tools made it possible to identify the infectious agent rapidly, to trace contamination chains in real time to enable effective interventions, and to develop a reliable serological tool for differential diagnoses. Today, equipped and functional facilities exist in both countries, led by Guinean and Congolese researchers trained to high levels of competence and benefiting from unique experience and field knowledge.
Asunto(s)
Enfermedades Transmisibles Emergentes , Técnicas y Procedimientos Diagnósticos , Epidemias/prevención & control , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/prevención & control , República Democrática del Congo/epidemiología , Guinea/epidemiología , HumanosRESUMEN
We assess the genetic relationships between 49 HIV-1 group O strains from 24 and 25 patients living in Cameroon and France, respectively. Strains were sequenced in four genomic regions: gag (p24) and three env regions (C2-V3, gp41, and for 22 C2-gp41). In each of the genomic regions analyzed, the genetic diversity among the group O strains was higher than that exhibited by group M. We characterize three major group O phylogenetic clusters (O:A, O:B, and O:C) that comprised the same virus strains in each of the genomic regions analyzed. The majority of strains cluster in O:A, a cluster previously identified by analysis of pol and env sequences. Group O recombinants were also identified. Importantly, the distinction between these three major group O clades was weak compared to the strong clustering apparent in the global group M phylogenetic tree that led to the identification of subtypes. Thus, these clusters of group O viruses should not be considered as equivalent to the group M subtypes. This difference between the pattern of group O and the global group M diversity, both taking into account the pandemic status of the group M subtypes and the comparatively small number of group O-infected individuals (the majority being from Cameroon), indicates that the group O phylogeny primarily represents viral divergence in the Cameroon region, analogous to group M viral diversity present in the Democratic Republic of Congo.
Asunto(s)
Variación Genética , Infecciones por VIH/epidemiología , VIH-1/clasificación , Epidemiología Molecular , Filogenia , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Camerún , Femenino , Francia , Genes env/genética , Proteína p24 del Núcleo del VIH/química , Proteína p24 del Núcleo del VIH/genética , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp41 de Envoltorio del VIH/química , Proteína gp41 de Envoltorio del VIH/genética , Infecciones por VIH/virología , VIH-1/genética , Humanos , Lactante , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Análisis de Secuencia de ADN , SerotipificaciónRESUMEN
We report a survey of HIV-1 group O infection in Cameroon during 1986 to 1998. The prevalence of HIV-1/O decreased from 0.6% to 0.4%, while HIV-1/M increased from 19.2% to 31.5% from 1994 to 1998. We concluded that HIV-1/O infection is stable in Cameroon and may be declining slightly.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , VIH-1/clasificación , Camerún/epidemiología , Humanos , Prevalencia , Factores de TiempoRESUMEN
Thus far, simian immunodeficiency virus from chimpanzees (SIVcpz) genomes have been characterized as Pan troglodytes troglodytes and show a strong relation with human immunodeficiency virus (HIV)-1 N in their env genes. We fully characterized another SIVcpz from P. t. troglodytes. This chimpanzee (Cam5) was, as was also the host of SIVcpz-cam3, wild born in Cameroon, a region where all three groups of HIV-1 (M, N and O) co-occur. In contrast to other SIVcpz, SIVcpz-cam5 was isolated immediately after the rescue of the animal. Our data demonstrate that SIVcpz-cam5, like SIVcpz-cam3, grows easily on human peripheral blood mononuclear cells (PBMCs) and uses CCR5 as a co-receptor similar to HIV-1 N YBF30. Phylogenetic analysis based on the entire env gene shows that SIVcpz-cam5 falls into the same unique subcluster as HIV-1 N YBF30, SIVcpz-cam3 and SIVcpz-US. A phylogenetic relationship was also found with the vif gene of HIV-1 N. This study provides proof that HIV-1 N related viruses circulate in wild P. t. troglodytes.
Asunto(s)
Genes env , VIH-1/fisiología , Filogenia , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/fisiología , Secuencia de Aminoácidos , Animales , Camerún , Secuencia de Consenso , ADN Viral/genética , Productos del Gen env/química , Productos del Gen env/genética , VIH-1/clasificación , VIH-1/genética , Humanos , Linfocitos/inmunología , Linfocitos/virología , Datos de Secuencia Molecular , Pan troglodytes , Reacción en Cadena de la Polimerasa , Receptores del VIH/fisiología , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Síndrome de Inmunodeficiencia Adquirida del Simio/sangre , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genéticaRESUMEN
Human immunodeficiency virus type 1 (HIV-1) group N from Cameroon is phylogenetically close, in env, to the simian immunodeficiency virus (SIV) cpz-gab from Gabon and SIVcpz-US of unknown geographic origin. We screened 29 wild-born Cameroonian chimpanzees and found that three (Cam3, Cam4, and Cam5) were positive for HIV-1 by Western blotting. Mitochondrial DNA sequence analysis demonstrated that Cam3 and Cam5 belonged to Pan troglodytes troglodytes and that Cam4 belonged to P. t. vellerosus. Genetic analyses of the viruses together with serological data demonstrated that at least one of the two P. t. troglodytes chimpanzees (Cam5) was infected in the wild, and revealed a horizontal transmission between Cam3 and Cam4. These data confirm that P. t. troglodytes is a natural host for HIV-1-related viruses. Furthermore, they show that SIVcpz can be transmitted in captivity, from one chimpanzee subspecies to another. All three SIVcpz-cam viruses clustered with HIV-1 N in env. The full Cam3 SIVcpz genome sequence showed a very close phylogenetic relationship with SIVcpz-US, a virus identified in a P. t. troglodytes chimpanzee captured nearly 40 years earlier. Like SIVcpz-US, SIVcpz-cam3 was closely related to HIV-1 N in env, but not in pol, supporting the hypothesis that HIV-1 N results from a recombination event. SIVcpz from chimpanzees born in the wild in Cameroon are thus strongly related in env to HIV-1 N from Cameroon, demonstrating the geographic coincidence of these human and simian viruses and providing a further strong argument in favor of the origin of HIV-1 being in chimpanzees.
Asunto(s)
Genes env , VIH-1/genética , Pan troglodytes/virología , Virus de la Inmunodeficiencia de los Simios/genética , Animales , Secuencia de Bases , Cartilla de ADN , Humanos , Datos de Secuencia Molecular , FilogeniaRESUMEN
While in the United States and northern Europe, human herpesvirus 8 (HHV-8) appears to be mainly sexually transmitted with primary infection occurring in adulthood, the modes of transmission remain unknown in East and Central Africa, where Kaposi's sarcoma (KS) is a long-standing endemic disease, occurring not only in adults but also in children. The aim of our present study was to determine the prevalence of HHV-8 infection in children from Yaounde, Cameroon, Central Africa. Specific antibodies directed against both latent and lytic HHV-8 antigens were detected and titrated, with an immunofluorescence assay using the KS-1 cell line, in the plasma of 258 children and adolescents, of 32 mother and child pairs and of 189 pregnant women. Two different HHV-8 DNA-specific sequences were searched in the buffy coat by PCR assays. The overall HHV-8 seroprevalence was 27.5% among these children and adolescents. In newborns, seroprevalence reached 46%, reflecting passive transmission of maternal IgG. This was followed by a marked drop. Then, beginning around 4 years of age, a regular increase of HHV-8 antibodies took place, reaching 39% in the 12- to 14-year age group and 48% above 15 years, a rate similar (54.5%) to that observed in pregnant women. PCR detection of HHV-8 sequences was negative in seronegative children and positive in the buffy coat in 17% of HHV-8-seropositive children, reflecting a low viral load in the peripheral blood. Our results establish that in Central Africa HHV-8 infection takes place during childhood by casual routes, in contrast to the sexual transmission observed in adults in northern Europe and the United States. We hypothesize that the lymphadenopathic form of KS seen in African children is related to an early and massive infection by HHV-8 in susceptible individuals.
Asunto(s)
Herpesvirus Humano 8 , Sarcoma de Kaposi/virología , Adolescente , Adulto , Camerún/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Reacción en Cadena de la Polimerasa , Embarazo , Prevalencia , Sarcoma de Kaposi/epidemiología , Pruebas SerológicasRESUMEN
Antibodies that are present in the serum of healthy individuals in the absence of deliberate immunization with any antigen, are refered to as natural antibodies. A vast majority of natural antibodies react with one or more self antigens and are termed as natural autoantibodies. The importance of natural autoantibodies in immune regulation has long been neglected, since tolerance to self was thought to be primarily dependent on the deletion of autoreactive clones, rather than on peripheral suppressive mechanisms. Clonal deletion and energy cannot account, however, for the prevalence of natural autoreactivity among healthy individuals. It is now well established that autoreactive antibodies and B cells, and autoreactive T cells, are present in healthy individuals, and in virtually all vertebrate species. Autoreactive repertoires are predominantly selected early in ontogeny. Questions pertaining to the role of natural antibodies in the regulation of the immune response and maintenance of immune homeostasis and to the distinction between natural autoreactivity and pathological autoimmunity have not been adequately addressed. Here, we focus on the current knowledge on the physicochemical and functional properties of NAA in man, and the use of NAA for therapeutic intervention. reserved.
Asunto(s)
Autoanticuerpos/inmunología , Autoanticuerpos/fisiología , Humanos , Inmunidad InnataRESUMEN
Given that normal individuals maintain significant levels of serum autoantibodies that share many characteristics with those found in association with autoimmune diseases (AID), it has been proposed that disease could result from defects in supraclonal regulation, namely deviations of normal patterns of immunoglobulin (Ig) connectivity. Using conventional methods, together with a recently developed technique to quantitatively score a variety of V-region-dependent serum IgG interactions, the authors have now compared serum Ig connectivity in a group of patients with systemic lupus erythematosus (SLE) to healthy controls. The results demonstrate the existence of V-region interactions of serum IgG and IgM in SLE patients and healthy donors, with comparable connectivity titres, diversity and average affinities (microM range), but a wider individual variation and a tendency for higher F(ab')2 directed reactivities in the group of SLE patients. Multivariate statistics analysis of the data derived from reactivity patterns on F(ab')2 subsets, however, distinguished the two groups of donors, and demonstrated a larger dispersion and wider time-dependent variations in the patient population, as compared to healthy controls. The authors conclude that SLE is associated with circulating antibody repertoires that deviate from the patterns and levels of V-region connectivity characteristic of healthy individuals. These findings may shed light on the mechanisms of disease maintenance, and on the basis for the therapeutic effects of normal polyclonal Igs at high doses.
Asunto(s)
Inmunoglobulinas/sangre , Lupus Eritematoso Sistémico/inmunología , Adolescente , Adulto , Anciano , Afinidad de Anticuerpos , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/sangre , Inmunoglobulina G/sangre , Región Variable de Inmunoglobulina/sangre , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana EdadRESUMEN
There is to date no quantitative method for scoring putative V-region interactions among serum antibodies, and the available qualitative techniques are not amenable to routine utilization. This deficit may explain the paucity of observations on the characteristics of the immune network, in contrast with the multiplicity of phenomenological descriptions on idiotype regulation. We describe here a novel methodology that uses isoelectric focusing (IEF) to resolve human F(ab')2 preparations from large pools of normal serum IgG into multiple bands, and computer-aided data processing to analyze interactions between the resulting blotted proteins and normal serum IgG from individual donors. Our results show that in all normal human sera tested, there are IgG-mediated interactions with a large number of IEF fractions of human F(ab')2. These interactions are V region specific, as assessed by inhibition experiments and by lack of binding of IgG monoclonal antibodies, and are characterized by average affinities that are in the micromolar range, as measured by surface plasmon resonance.
Asunto(s)
Inmunoglobulina G/sangre , Inmunoglobulina G/química , Región Variable de Inmunoglobulina/sangre , Región Variable de Inmunoglobulina/química , Afinidad de Anticuerpos , Especificidad de Anticuerpos , Humanos , Fragmentos Fab de Inmunoglobulinas/sangre , Fragmentos Fab de Inmunoglobulinas/química , Focalización IsoeléctricaRESUMEN
We describe herein the refined high resolution x-ray structures of two components of the bacterial cell wall, muramic acid and muramyl dipeptide complexed to isolectin I from Lathyrus ochrus seeds. In both complexes, only the ring hydroxyl oxygen atoms of the bound sugar establish direct hydrogen bonds with isolectin I, as in the case of all the previously determined monosaccharide-lectin complexes. In addition, the lactyl methyl of both components strongly interacts via hydrophobic contacts with the side chains of residues Tyr100 and Trp128 of isolectin I, which could explain the higher affinity of isolectin I for muramic acid as compared with glucose. These 2 residues, however, are not involved in the stabilization of the oligosaccharide-isolectin I complexes. The dipeptide (D-Ala-D-iGln) of the second component is in stacking interaction with the N-acetyl group of glucose and with loop Gly97-Gly98 of isolectin I. In addition to these van der Waals' contacts, the dipeptide interacts with the lectin via well ordered water molecules also. Superposition of the structures of the muramyl dipeptide complex and of the muramic acid complex shows that the glucose ring in the dipeptide compound is tilted by about 15 degrees in comparison with that of muramic acid. The fact that the lactyl group has the same confrontation in both components reveals that the lectin is stereospecific and recognizes only diastereoisomer S of this group, which better fits the saccharide-binding site.
Asunto(s)
Acetilmuramil-Alanil-Isoglutamina/química , Lectinas/química , Ácidos Murámicos/química , Lectinas de Plantas , Secuencia de Aminoácidos , Bacterias , Sitios de Unión , Conformación de Carbohidratos , Pared Celular/metabolismo , Cromatografía de Afinidad , Cristalización , Cristalografía por Rayos X , Dipéptidos/química , Glucosa/química , Enlace de Hidrógeno , Lectinas/aislamiento & purificación , Modelos Moleculares , Datos de Secuencia Molecular , Monosacáridos , Conformación Proteica , EstereoisomerismoRESUMEN
Various monosaccharides and oligosaccharides were used to define the specificity of the Butea frondosa lectin using the hapten inhibition technique of human erythrocyte agglutination. Although B. frondosa lectin exhibited higher affinity for N-acetylgalactosamine, lactose and N-acetyllactosamine appeared to be relatively good inhibitors of haemagglutination. The behaviour of N-acetyllactosamine-type oligosaccharides and glycopeptides on a column of B. frondosa lectin immobilized on Sepharose 4B showed that the sugar-binding specificity of the lectin is directed towards unmasked N-acetyllactosamine sequences. Substitution of these N-acetyllactosamine sequences by sialic acid residues completely abolished the affinity of the lectin for the saccharides. The presence of one or several alpha Fuc(1-3)GlcNAc groups completely inhibited the interaction between the glycopeptides and the lectin. Substitution of the core beta-mannose residue by an additional bisecting beta(1-4)GlcNAc residue decreases the affinity of the lectin for these structures as compared with the unsubstituted ones.
Asunto(s)
Lectinas/metabolismo , Monosacáridos/metabolismo , Oligosacáridos/metabolismo , Secuencia de Carbohidratos , Glicoproteínas/metabolismo , Pruebas de Inhibición de Hemaglutinación , Lectinas/aislamiento & purificación , Datos de Secuencia Molecular , Lectinas de Plantas , Semillas/metabolismo , Especificidad por SustratoRESUMEN
The inhibitory potency of both muramic acid (MurAc) and N-acetylmuramic acid (MurNAc) on various legume lectins, including Glc/Man- and Gal/GalNAc-specific lectins, was investigated by a haemagglutination inhibition technique. Data indicated that many lectins, especially those specific for Glc/Man, specifically interact with MurAc and MurNAc often to a greater extent than with other monosaccharides and their derivatives, such as N-acetylglucosamine (GlcNAc) and sialic acid. Glc/Man-specific lectins were also shown to interact with the muramyl-dipeptide MurNAc-D-Ala-D-isoGln. These interactions could explain why various lectins readily agglutinate some bacterial strains of which cell walls contain peptidoglycans with high amounts of MurNAc.