RESUMEN
Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. Moreover, seven different guenons (Cercopithecus spp.) shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/genética , Antígenos CD4/genética , Catarrinos/genética , Catarrinos/virología , Variación Genética , VIH , Síndrome de Inmunodeficiencia Adquirida del Simio/genética , Virus de la Inmunodeficiencia de los Simios , Alelos , Animales , Antígenos CD4/química , Evolución Molecular , Productos del Gen env/química , Humanos , Unión Proteica , Dominios ProteicosRESUMEN
BACKGROUND: Gabon is an endemic area for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and the risk of co-infection is high. METHOD: Between November 2015 and April 2016, we conducted retrospective study on HCV infection among people living with HIV/AIDS (PLHA). A total of 491 PLHA were included in this study and tested for the presence of HCV infection. HIV viral loads were obtained using the Generic HIV viral Load® assay and the CD4+ T cells count was performed using BD FACSCount™ CD4 reagents. HCV screening was performed using the MP Diagnostics HCV ELISA 4.0 kit. HCV genotypes were determined by sequence analysis of NS5B and Core regions. The Mann-Whitney test was used to compare the groups. Chi-2 test and Fisher's Exact Test were used to compare prevalence. RESULTS: HCV seroprevalence was 2.9% (14/491), (95% confidence interval (CI):1.4-4.3%). The percentage of HCV viremic patients, defined by the detection of HCV RNA in plasma, was 57% (8/14), representing 1.6% of the total population. HCV seroprevalence and replicative infection were not statistically differ with gender. The percentage of co-infection increased with age. No correlation with CD4+ T cells count and HIV viral load level was registered in this study. Identified HCV strains were predominantly of genotype 4 (87.5%) including 4k, 4e, 4g, 4p, 4f and 4c subtypes. Only one strain belonged to genotype 2 (subtype 2q). Analysis of the NS5B region did not reveal the presence of resistance-associated substitutions for sofosbuvir. CONCLUSION: A systematic screening of hepatitis C is therefore strongly recommended as well as genotyping of HCV strains in order to adapt treatments for the specific case of people living with HIV/AIDS in Central Africa.
Asunto(s)
Genotipo , Infecciones por VIH/epidemiología , Hepacivirus/genética , Hepatitis C/epidemiología , Adolescente , Adulto , Recuento de Linfocito CD4 , Femenino , Gabón/epidemiología , Genes Virales , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/genética , VIH-1/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Carga Viral , Adulto JovenRESUMEN
In Gabon, a central African country, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are endemic. In a recent study, conducted in a semi-urban area (Franceville, Gabon), HBV infection was found to be more prevalent among HIV infected individuals. This study aims to investigate the prevalence and genetic diversity of hepatitis B virus infection among HIV infected individuals, predominantly under antiretroviral therapy, living in fully urbanized area: Libreville, capital of Gabon. Serological and molecular tests were performed to detect HBV infection among patients living with HIV/AIDS (PLHA). We used Monolisa HBsAg ULTRA, Anti-HBc Plus and Anti-HBs Plus EIA kits for serological analyses. HBV DNA viral load (HBV DNA VL) was determined by real time PCR and molecular characterization of HBV strains was performed by sequencing and phylogenetic analysis of partial HBV surface and core genes. At all, 70.2% of patients were under antiretroviral therapy. The prevalence of HBsAg was 8.8% (43/487). Detectable HBV DNA was found in 69.7% (30/43) of HBsAg positive patients and in 17.5% (24/137) HBsAg negative patients. HBV DNA VL was significantly higher among patient with CD4 cell counts less than 200 cells/mm3 than those with CD4 cell counts greater than 500 cells/mm3 (p = 0.008). We confirmed the presence of HBV sub-genotypes QS-A3 (40%), and A4 (20%) and HBV-E genotype (40%). The percentage of resistance to Lamivudine was high (40%) and varied according to the M204V/I motif. Occult hepatitis B infection (OBI) was found in patients with isolated HBcAb and among patients who had completed their HBsAg seroconversion. We detected HBV DNA for one patient without any HBV serological marker. This study provides a new landmark for the comprehension of HBV infection in PLHA in urban areas. OBI enhances HBV DNA prevalence and should be investigated in all HBsAg negative individuals.
Asunto(s)
ADN Viral/aislamiento & purificación , Infecciones por VIH/complicaciones , Virus de la Hepatitis B/genética , Hepatitis B/complicaciones , Adolescente , Adulto , Recuento de Linfocito CD4 , Femenino , Gabón/epidemiología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Carga Viral , Adulto JovenRESUMEN
Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.
Asunto(s)
Coinfección , Genotipo , Infecciones por VIH/virología , Virus de la Hepatitis B/genética , Hepatitis B/virología , Mutación , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Gabón/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Seropositividad para VIH , VIH-1/inmunología , Hepatitis B/epidemiología , Hepatitis B/inmunología , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de la Hepatitis B/genética , Antígenos de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Prevalencia , Análisis de Secuencia de ADN , Carga ViralRESUMEN
Hepatitis B virus (HBV) and hepatitis delta virus (HDV) occur worldwide and are prevalent in both urban and remote rural communities. In a remote village in Gabon, central Africa, we observed a high prevalence of HBsAg carriage and HDV infection, particularly in children and adolescents. The prevalence of HBsAg differed significantly by gender and age, females being more likely than males to carry the HBsAg during the first 10 years of life, while the prevalence was higher among males than females aged 11-20 years. We also characterised HBV and HDV strains circulating in the village. The principal HBV strains belonged to genotype HBV-E and subgenotype QS-A3. Complete genome analysis revealed for the first time the presence of the HBV-D genotype in Gabon, in the form of an HBV-D/E recombinant. Molecular analysis of HDV strains and their complete genomic characterisation revealed two distinct groups within the dominant HDV clade 8. Molecular analysis of HBV and HDV strains did not reveal vertical transmission within the families studied but rather horizontal, intrafamilial transmission among children aged 0-10 years. Our findings indicate that HBV is transmitted in early childhood by body fluids rather than by sexual contact. Health education adapted to the different age groups might therefore help to reduce HBV transmission. Young children should be vaccinated to control HBV infection in areas of extremely high prevalence.
Asunto(s)
Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis B/transmisión , Hepatitis D/epidemiología , Hepatitis D/transmisión , Virus de la Hepatitis Delta/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Coinfección/virología , Femenino , Gabón/epidemiología , Genotipo , Hepatitis B/inmunología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/inmunología , Hepatitis D/inmunología , Hepatitis D/virología , Virus de la Hepatitis Delta/clasificación , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Población Rural , Adulto JovenRESUMEN
Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates.
Asunto(s)
Coinfección/veterinaria , Infecciones por Deltaretrovirus/veterinaria , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Animales , Coinfección/complicaciones , Coinfección/inmunología , Coinfección/virología , Infecciones por Deltaretrovirus/complicaciones , Infecciones por Deltaretrovirus/inmunología , Infecciones por Deltaretrovirus/virología , Mandrillus , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Subgrupos de Linfocitos T/inmunología , Carga ViralRESUMEN
Studies of primate lentiviruses continue to provide information about the evolution of simian immunodeficiency viruses (SIVs) and the origin and emergence of HIV since chimpanzees in west-central Africa (Pan troglodytes troglodytes) were recognized as the reservoir of SIVcpzPtt viruses, which have been related phylogenetically to HIV-1. Using in-house peptide ELISAs to study SIV prevalence, we tested 104 wild-born captive chimpanzees from Gabon and Congo. We identified two new cases of SIVcpz infection in Gabon and characterized a new SIVcpz strain, SIVcpzPtt-Gab4. The complete sequence (9093 bp) was obtained by a PCR-based 'genome walking' approach to generate 17 overlapping fragments. Phylogenetic analyses of separated genes (gag, pol-vif and env-nef) showed that SIVcpzPtt-Gab4 is closely related to SIVcpzPtt-Gab1 and SIVcpzPtt-Gab2. No significant variation in viral load was observed during 3 years of follow-up, but a significantly lower CD4+ T cells count was found in infected than in uninfected chimpanzees (p<0.05). No clinical symptoms of SIV infection were observed in the SIV-positive chimpanzees. Further field studies with non-invasive methods are needed to determine the prevalence, geographic distribution, species association, and natural history of SIVcpz strains in the chimpanzee habitat in Gabon.
Asunto(s)
Animales Salvajes/virología , Pan troglodytes/virología , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , África Central , Secuencia de Aminoácidos , Animales , Animales Salvajes/inmunología , Western Blotting , Femenino , Genes env , Genoma Viral/genética , Geografía , Masculino , Datos de Secuencia Molecular , Pan troglodytes/inmunología , Filogenia , ARN Viral/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/sangre , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/inmunología , Virus de la Inmunodeficiencia de los Simios/fisiología , Proteínas Virales/química , Proteínas Virales/genética , Replicación Viral/fisiologíaRESUMEN
Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.
Asunto(s)
Predisposición Genética a la Enfermedad , Mandrillus/fisiología , Síndrome de Inmunodeficiencia Adquirida del Simio/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Conducta Social , Agresión , Animales , Anticuerpos Antivirales/sangre , Teorema de Bayes , Femenino , Gabón/epidemiología , Inmunoensayo , Estudios Longitudinales , Masculino , Modelos Biológicos , Estaciones del Año , Conducta Sexual Animal , Síndrome de Inmunodeficiencia Adquirida del Simio/sangre , Síndrome de Inmunodeficiencia Adquirida del Simio/epidemiología , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genéticaRESUMEN
Simian immunodeficiency virus (SIV) infection in African nonhuman primate (NHP) natural hosts is usually nonpathogenic, despite high levels of virus replication. We have previously shown that chronic SIV infection in sooty mangabeys (SMs) and African green monkeys (AGMs) is associated with low levels of immune activation and bystander T cell apoptosis. To compare these features with those observed in another natural host, the mandrill (MND), we conducted a cross-sectional survey of the 23 SIV-infected and 25 uninfected MNDs from the only semifree colony of mandrills available worldwide. Viral loads (VLs) were determined and phenotypic and functional analysis of peripheral blood- and lymph node-derived lymphocytes was performed. We found that mandrills chronically infected with SIVmnd-1 or SIVmnd-2 have similar levels of viral replication, and we observed a trend toward lower CD4+ T cell counts in chronically SIVmnd-2-infected MNDs than SIVmnd-1-infected MNDs. No correlation between CD4+ T cell counts and VLs in SIV-infected MNDs could be established. Of note, the levels of T cell activation, proliferation, and apoptosis were comparable between SIVmnd-1- and SIVmnd-2-infected MNDs and to those observed in uninfected animals, with the only exception being an increase in tumor necrosis factor alpha-producing CD8+ T cells in SIVmnd-2-infected MNDs. Overall, these findings recapitulate previous observations in SIV-infected SMs and AGMs and lend further evidence to the hypothesis that low levels of immune activation protect natural SIV hosts from disease progression.
Asunto(s)
Mandrillus/inmunología , Mandrillus/virología , Enfermedades de los Primates/inmunología , Enfermedades de los Primates/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Animales , Apoptosis , Sangre/inmunología , Recuento de Linfocito CD4 , Proliferación Celular , Estudios Transversales , Ganglios Linfáticos/inmunología , Activación de Linfocitos , Linfocitos/inmunología , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genética , Virus de la Inmunodeficiencia de los Simios/inmunología , Carga ViralRESUMEN
Simian immunodeficiency virus (SIV) lineages have been identified that are endemic to Bioko Island. The time the island formed offers a geological time scale calibration point for dating the most recent common ancestor of SIV. The Bioko viruses cover the whole range of SIV genetic diversity, and each Bioko SIV clade is most closely related to viruses circulating in hosts of the same genus on the African mainland rather than to SIVs of other Bioko species. Our phylogeographic approach establishes that SIV is ancient and at least 32,000 years old. Our conservative calibration point and analyses of gene sequence saturation and dating bias suggest it may be much older.
Asunto(s)
Cercopithecidae/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genética , Animales , Cercopithecus/virología , Colobus/virología , Guinea Ecuatorial , Evolución Molecular , Genes pol , Variación Genética , Geografía , Mandrillus/virología , Datos de Secuencia Molecular , Filogenia , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Factores de TiempoRESUMEN
We used mandrills (Mandrillus sphinx) naturally infected with simian T-cell leukemia virus type 1 (STLV-1) as a model for evaluating the influence of natural STLV-1 infection on the dynamics and evolution of the immune system during chronic infection. Furthermore, in order to evaluate the role of the immune system in controlling the infection during latency, we induced immunosuppression in the infected monkeys. We first showed that the STLV-1 proviral load was higher in males than in females and increased significantly with the duration of infection: mandrills infected for 10-6 years had a significantly higher proviral load than those infected for 2-4 years. Curiously, this observation was associated with a clear reduction in CD4+ T-cell number with age. We also found that the percentage of CD4(+) T cells co-expressing the activation marker HLA-DR and the mean percentage of CD25(+) in CD4(+) and CD8(+) T cells were significantly higher in infected than in uninfected animals. Furthermore, the STLV-1 proviral load correlated positively with T-cell activation but not with the frequency of T cells secreting interferon gamma in response to Tax peptides. Lastly, we showed that, during immunosuppression in infected monkeys, the percentages of CD8(+) T cells expressing HLA-DR(+) and of CD4(+) T cells expressing the proliferation marker Ki67 decreased significantly, although the percentage of CD8(+) T cells expressing HLA-DR(+) and Ki67 increased significantly by the end of treatment. Interestingly, the proviral load increased significantly after immunosuppression in the monkey with the highest load. Our study demonstrates that mandrills naturally infected with STLV-1 could be a suitable model for studying the relations between host and virus. Further studies are needed to determine whether the different compartments of the immune response during infection induce the long latency by controlling viral replication over time. Such studies would provide important information for the development of immune-based therapeutic strategies.
Asunto(s)
Inmunosupresores/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus Linfotrópico T Tipo 1 de los Simios/inmunología , Linfocitos T/inmunología , Linfocitos T/virología , Carga Viral , Animales , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/virología , Femenino , Citometría de Flujo/métodos , Antígenos HLA-DR/metabolismo , Interferón gamma/metabolismo , Subunidad alfa del Receptor de Interleucina-2/biosíntesis , Masculino , Mandrillus , Tacrolimus/uso terapéuticoRESUMEN
The prevalence of hepatitis B virus (HBV) surface antigen was significantly higher in urban (12.9%) than in rural (7.6%) populations (P = 0.003), but no difference was found in the prevalence of hepatitis delta virus (HDV), which was high in both populations. Phylogenetic analysis showed the circulation of HBV-A3 and -E genotypes and the presence of HDV-1, HDV-7, and HDV-8 clades.
Asunto(s)
Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis D/epidemiología , Virus de la Hepatitis Delta/clasificación , Virus de la Hepatitis Delta/genética , Polimorfismo Genético , Adolescente , Adulto , África Central/epidemiología , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Femenino , Gabón/epidemiología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis D/virología , Virus de la Hepatitis Delta/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Prevalencia , Población Rural , Análisis de Secuencia de ADN , Homología de Secuencia , Población Urbana , Adulto JovenRESUMEN
BACKGROUND: Although a wide variety of non-human primates are susceptible to simian T-cell leukaemia virus type 1 (STLV-1), little is known about the virological or molecular determinants of natural STLV-1 infection. METHODS: We determined STLV-1 virus tropism in vivo and its relation to the immune response by evaluating cytokine production and T-cell subsets in naturally infected and uninfected mandrills. RESULTS: With real-time PCR methods, we found that STLV-1 in mandrills infects both CD4(+) and CD8(+) T cells; however, proviral loads were significantly higher (P = 0.01) in CD4(+) than in CD8(+) cells (mean STLV-1 copies number per 100 cells (+/- SD) was 7.8 +/- 8 in CD4(+) T cells and 3.9 +/- 4.5 in CD8(+) T cells). After culture, STLV-1 provirus was detected in enriched CD4(+) but not in enriched CD8(+) T cells. After 6 months of culture, STLV-1-transformed cell lines expressing CD3(+), CD4(+) and HLADR(+) were established, and STLV-1 proteins and tax/rex mRNA were detected. In STLV-1 infected monkeys, there was a correlation between high proviral load and elevated levels of interleukin (IL)-2, IL-6, IL-10, interferon-gamma and tumour necrosis factor-alpha. The two monkeys with the highest STLV-1 proviral load had activated CD4(+)HLADR(+) and CD8(+)HLADR(+) T-cell subsets and a high percentage of CD25(+) in CD4(+) and CD8(+) T cells. CONCLUSIONS: Our study provides the first cellular, immunological and virological characterization of natural STLV-1 infection in mandrills and shows that they are an appropriate animal model for further physiopathological studies of the natural history of human T-cell leukaemia viruses.
Asunto(s)
Citocinas/metabolismo , Mandrillus , Virus Linfotrópico T Tipo 1 de los Simios/inmunología , Linfocitos T/fisiología , Animales , Anticuerpos , Células Cultivadas , Enfermedad Crónica , Perfilación de la Expresión Génica , Regulación Viral de la Expresión Génica/fisiología , Reacción en Cadena de la Polimerasa/veterinaria , Linfocitos T/citología , Carga ViralRESUMEN
OBJECTIVE: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV. DESIGN: : Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251. METHODS: ZDV/3TC/IDV treatment was initiated 4 h after exposure and continued for 28 days. Groups of six animals received a placebo or a combination of oral ZDV (4.5 mg/kg), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily or subcutaneous ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) twice daily, and a higher dose of IDV (60 mg/kg) administered orally twice daily. RESULTS: In the placebo group, all animals were infected. Antiretroviral association protected one of the six animals if all drugs were administered orally and four of the six animals if ZDV and 3TC were administered subcutaneously and IDV was given orally at triple dose. In infected animals, viremia was significantly delayed and lowered in treated animals than in animals given placebo, and high CD4 cell counts were maintained in the treated animals, at least in the medium term. Antiretroviral dosages made in macaques receiving the same treatments showed that protection efficacy could be linked to antiretroviral plasmatic concentration. CONCLUSION: This study shows, for the first time in macaques, that the postexposure prophylaxis recommended for humans may be effective after vaginal exposure. Improvements in pharmacokinetic parameters significantly increased treatment efficiency.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Enfermedades Virales de Transmisión Sexual/prevención & control , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Administración Oral , Animales , Fármacos Anti-VIH/sangre , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Femenino , Indinavir/sangre , Indinavir/uso terapéutico , Inyecciones Subcutáneas , Lamivudine/sangre , Lamivudine/uso terapéutico , Macaca fascicularis , Enfermedades Virales de Transmisión Sexual/inmunología , Enfermedades Virales de Transmisión Sexual/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Vagina/virología , Carga Viral , Viremia/prevención & control , Zidovudina/sangre , Zidovudina/uso terapéuticoRESUMEN
The mandrill (Mandrillus sphinx) is naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd types 1 and 2. Both of these viruses cause long-term, non-progressive infections in their natural host despite high plasma viral loads. This study assessed the susceptibility of rhesus macaques to infection by these two types of SIVmnd and compared the virological and basic immunological characteristics of the resulting infections with those observed in natural infection in mandrills. Whilst both SIVmnd types induced similar levels of virus replication during acute infection in both mandrills and macaques, they produced a more pronounced CD4(+) T-cell depletion in rhesus macaques that persisted longer during the initial stage of infection. Pro-inflammatory cytokine responses were also induced at higher levels in rhesus macaques early in the infection. During the chronic phase of infection in mandrills, which in this case was followed for up to 2 years after infection, high levels of chronic virus replication did not induce significant changes in CD4(+) or CD8(+) T-cell counts. In rhesus macaques, the overall chronic virus replication level was lower than in mandrills. At the end of the follow-up period, although the viral loads of SIVmnd-1 and SIVmnd-2 were relatively similar in rhesus macaques, only SIVmnd-1-infected rhesus macaques showed significant CD4(+) T-cell depletion, in the context of higher levels of CD4(+) and CD8(+) T-cell activation, compared with SIVmnd-infected mandrills. The demonstration of the ability of both SIVmnd types to induce persistent infections in rhesus macaques calls for a careful assessment of the potential of these two viruses to emerge as new human pathogens.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Macaca mulatta/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Animales , Formación de Anticuerpos , Cartilla de ADN , Femenino , Haplorrinos/virología , Hominidae/virología , Activación de Linfocitos/inmunología , Depleción Linfocítica , Masculino , Mandrillus/virología , ARN Viral/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/epidemiología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/clasificación , Especificidad de la EspecieRESUMEN
Miners in sub-Saharan African are known to have an extremely high prevalence of HIV-1 infection. We therefore evaluated the prevalence of HIV-1 infection among manganese miners in Gabon, central Africa and examined the diversity of HIV-1 strains by characterizing the polymorphism of the pol gene in order to observe drug resistance-associated mutations. In 857 samples tested, the HIV-1 prevalence was 2.9%. By pol sequence analysis, we showed that all the HIV-1 strains belonged to group M, with a majority of CRF02_AG (57%) followed by subtype A (9%) and CRF01_AE or subtype B (4%). The remaining HIV-1 strains demonstrated discordant genomic results and exhibited a mosaic pol genome (30%). Most of the mutations detected in pol coding regions corresponded to the subtype polymorphism, with no specific antiretroviral drug resistance. To avoid the rapid emergence of resistant viruses in this part of central Africa, continuous surveillance of the circulation of drug-resistant viruses must be maintained to guide treatment strategies.
Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Mutación Missense , Adulto , Fármacos Anti-VIH/farmacología , Femenino , Gabón/epidemiología , VIH-1/clasificación , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Polimorfismo Genético , Análisis de Secuencia de ADN , Estudios Seroepidemiológicos , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
Simian immunodeficiency virus (SIV) persistence in wild populations of African nonhuman primates (NHPs) may occur through horizontal and vertical transmission. However, the mechanism(s) and timing of the latter type of transmission have not been investigated to date. Here we present the first study of SIV transmissibility by breast-feeding in an African NHP host. Six mandrill dames were infected with plasma containing 300 50% tissue culture infective doses of SIVmnd-1 on the day after delivery. All female mandrills became infected, as demonstrated by both plasma viral loads (VLs) and anti-SIVmnd-1 seroconversion. Neither fever nor lymphadenopathy was observed. At the peak of SIVmnd-1 viral replication (days 7 to 10 postinoculation), plasma VLs were high (8 x 10(6) to 8 x 10(8) RNA copies/ml) and paralleled the high VLs in milk (4.7 x 10(4) to 5.6 x 10(5) RNA/ml). However, at the end of the breast-feeding period, after 6 months of follow-up, no sign of infection was observed for the offspring. Later on, during a 4-year follow-up examination, two of the offspring showed virological evidence of SIVmnd-1 infection. Both animals seroconverted at least 6 months after the interruption of lactation. In conclusion, despite extensive viral replication in mandrill mothers and high levels of free virus in milk, no SIVmnd-1 transmission was detectable at the time of breast-feeding or during the following months. Since we observed a markedly lower expression of CCR5 on the CD4(+) T cells of young mandrills and African green monkeys than on those of adults, we propose that low levels of this viral coreceptor on CD4(+) T cells may be involved in the lack of breast-feeding transmission in natural hosts of SIVs.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Conducta Alimentaria/fisiología , Mandrillus/inmunología , Mandrillus/virología , Receptores CCR5/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Femenino , Dosificación de Gen/genética , Recuento de Linfocitos , Leche/metabolismo , Leche/virología , ARN Viral/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Síndrome de Inmunodeficiencia Adquirida del Simio/virologíaRESUMEN
Hepatitis B virus (HBV) surface antigen (HBsAg) was found in 9.2% of 1,186 pregnant women from Gabon, of whom 10.1% had the HBe antigen and 89.9% had anti-HBe antibodies. Antibodies to the hepatitis delta virus (HDV) were found in 15.6% of the HBsAg-positive women. The HBV strains were of the A3 and E genotypes. The HDV strains belonged to HDV clades 1 and 8. These results provide clear evidence that HDV clade 8 is indigenous to Africa.
Asunto(s)
Enfermedades Endémicas , Variación Genética , Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis D/epidemiología , Virus de la Hepatitis Delta/genética , Adolescente , Adulto , Análisis por Conglomerados , Gabón/epidemiología , Anticuerpos Antihepatitis/sangre , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis D/virología , Virus de la Hepatitis Delta/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Filogenia , Mujeres Embarazadas , Análisis de Secuencia de ADN , Estudios SeroepidemiológicosRESUMEN
In order to determine whether geographical or species clustering accounts for the distribution of hepatitis B virus (HBV) in subspecies of chimpanzees in Africa, four complete chimpanzee HBV (ChHBV) genome sequences were obtained from eight hepatitis B surface antigen-positive wild-born chimpanzees from Cameroon, Republic of Congo and Gabon. The serological profiles of these chimpanzees corresponded to the acute or chronic highly replicative phase of HBV infection, as confirmed by high plasma HBV loads. Analysis of the sequence alignment of 256 aa (S region) from the eight HBV-infected chimpanzees allowed us to determine the HBV amino acid patterns specific to each chimpanzee subspecies and to their geographical origin. Phylogenetic analysis of both the S region and the complete genome confirmed this distinctive clustering of eight novel ChHBV strains within Pan troglodytes. The strong phylogenetic associations of ChHBV sequences with both chimpanzee subspecies and their geographical origin were therefore confirmed.