RESUMEN
BACKGROUND: Simian T-cell leukemia virus type 1 (STLV-1) is a retrovirus closely related to human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia (ATL). It has been shown that Japanese macaques (Macaca fuscata, JMs) are one of the main hosts of STLV-1 and that a high percentage of JMs (up to 60%) are infected with STLV-1; however, the molecular epidemiology of STLV-1 in JMs has not been examined. METHODS: In this study, we analyzed full-length STLV-1 genome sequences obtained from 5 independent troops including a total of 68 JMs. RESULTS: The overall nucleotide heterogeneity was 4.7%, and the heterogeneity among the troops was 2.1%, irrespective of the formation of distinct subclusters in each troop. Moreover, the heterogeneity within each troop was extremely low (>99% genome homology) compared with cases of STLV-1 in African non-human primates as well as humans. It was previously reported that frequent G-to-A single-nucleotide variants (SNVs) occur in HTLV-1 proviral genomes in both ATL patients and HTLV-1 carriers, and that a G-to-A hypermutation is associated with the cellular antiviral restriction factor, Apobec3G. Surprisingly, these SNVs were scarcely observed in the STLV-1 genomes in JMs. CONCLUSIONS: Taken together, these results indicate that STLV-1 genomes in JMs are highly homologous, at least in part due to the lack of Apobec3G-dependent G-to-A hypermutation.
Asunto(s)
Genoma Viral , Macaca fuscata , Virus Linfotrópico T Tipo 1 de los Simios , Animales , Virus Linfotrópico T Tipo 1 de los Simios/genética , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Macaca fuscata/genética , Filogenia , Estudios de Cohortes , Infecciones por Deltaretrovirus/virología , Infecciones por Deltaretrovirus/veterinaria , Infecciones por Deltaretrovirus/epidemiología , Japón , Humanos , Análisis de Secuencia de ADN , Epidemiología Molecular , Variación GenéticaRESUMEN
BACKGROUND: Primate T-lymphotropic viruses type 1 (PTLV-1) are complex retroviruses infecting both human (HTLV-1) and simian (STLV-1) hosts. They share common epidemiological, clinical and molecular features. In addition to the canonical gag, pol, env retroviral genes, PTLV-1 purportedly encodes regulatory (i.e. Tax, Rex, and HBZ) and accessory proteins (i.e. P12/8, P13, P30). The latter have been found essential for viral persistence in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We have isolated a STLV-1 virus from a bonnet macaque (Macaca radiata-Mra18C9), a monkey from India. The complete sequence was obtained and phylogenetic analyses were performed. The Mra18C9 strain is highly divergent from the known PTLV-1 strains. Intriguingly, the Mra18C9 lacks the 3 accessory open reading frames. In order to determine if the absence of accessory proteins is specific to this particular strain, a comprehensive analysis of the complete PTLV-1 genomes available in Genbank was performed and found that the lack of one or many accessory ORF is common among PTLV-1. CONCLUSION: This study raises many questions regarding the actual nature, role and importance of accessory proteins in the PTLV-1 biology.
Asunto(s)
Infecciones por Deltaretrovirus/veterinaria , Macaca radiata/virología , Sistemas de Lectura Abierta , Virus Linfotrópico T Tipo 1 de los Simios/genética , Proteínas Reguladoras y Accesorias Virales/genética , Animales , Infecciones por Deltaretrovirus/virología , India , Filogenia , Análisis de Secuencia de ADN , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificaciónRESUMEN
Simian T-Leukemia Virus type 1 and Simian Foamy Virus infect non-human primates. While STLV-1, as HTLV-1, causes Adult T-cell Leukemia/lymphoma, SFV infection is asymptomatic. Both retroviruses can be transmitted from NHPs to humans through bites that allow contact between infected saliva and recipient blood. Because both viruses infect CD4+ T-cells, they might interfere with each other replication, and this might impact viral transmission. Impact of STLV-1 co-infection on SFV replication was analyzed in 18 SFV-positive/STLV-1-negative and 18 naturally SFV/STLV-1 co-infected Papio anubis. Even if 9 animals were found STLV-1-positive in saliva, STLV-1 PVL was much higher in the blood. SFV proviruses were detected in the saliva of all animals. Interestingly, SFV proviral load was much higher in the blood of STLV-1/SFV co-infected animals, compared to STLV-1-negative animals. Given that soluble Tax protein can enter uninfected cells, we tested its effect on foamy virus promoter and we show that Tax protein can transactivate the foamy LTR. This demonstrates that true STLV-1 co-infection or Tax only has an impact on SFV replication and may influence the ability of the virus to be zoonotically transmitted as well as its ability to promote hematological abnormalities.
Asunto(s)
Coinfección/virología , Infecciones por Deltaretrovirus/virología , Infecciones por Retroviridae/virología , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Virus Espumoso de los Simios/aislamiento & purificación , Carga Viral , Animales , Sangre/virología , Infecciones por Deltaretrovirus/complicaciones , Transmisión de Enfermedad Infecciosa , Papio anubis , Provirus/aislamiento & purificación , Infecciones por Retroviridae/complicaciones , Saliva/virología , Replicación ViralRESUMEN
Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8+ T cell recognition were not observed, premature stop codons were observed in 7% and 56% of tax sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively.IMPORTANCE It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A preventive vaccine would significantly impact the global burden associated with HTLV infections. Here we provide fundamental information on the simian T lymphotropic virus (STLV) naturally transmitted in a colony of captive baboons. The limited viral sequence heterogeneity in individual baboons, the identity of the viral gene product that is the major target of cellular immune responses, the persistence of viral amino acid sequences that are the major targets of cellular immune responses, and the emergence in vivo of truncated variants in the major target of cellular immune responses all parallel what are seen with HTLV infection of humans. These results justify the use of STLV-infected baboons as a model system for vaccine development efforts.
Asunto(s)
Productos del Gen tax/química , Productos del Gen tax/genética , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Linfocitos T/inmunología , Sustitución de Aminoácidos , Animales , ADN Viral/genética , Productos del Gen tax/inmunología , Genoma Viral , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/transmisión , Secuenciación de Nucleótidos de Alto Rendimiento , Inmunidad Celular , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Papio anubis , Filogenia , Reacción en Cadena de la Polimerasa , Virus Linfotrópico T Tipo 1 de los Simios/inmunología , Linfocitos T/virología , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Simian T-lymphotropic virus 1 (STLV-1) enters human populations through contact with nonhuman primate (NHP) bushmeat. We tested whether differences in the extent of contact with STLV-1-infected NHP bushmeat foster regional differences in prevalence of human T-lymphotropic virus 1 (HTLV-1). Using serological and PCR assays, we screened humans and NHPs at two Sub-Saharan African sites where subsistence hunting was expected to be less (Taï region, Côte d'Ivoire [CIV]) or more (Bandundu region, Democratic Republic of the Congo [DRC]) developed. Only 0.7% of human participants were infected with HTLV-1 in CIV (n = 574), and 1.3% of humans were infected in DRC (n = 302). Two of the Ivorian human virus sequences were closely related to simian counterparts, indicating ongoing zoonotic transmission. Multivariate analysis of human demographic parameters and behavior confirmed that participants from CIV were less often exposed to NHPs than participants from DRC through direct contact, e.g., butchering. At the same time, numbers of STLV-1-infected NHPs were higher in CIV (39%; n = 111) than in DRC (23%; n = 39). We conclude that similar ultimate risks of zoonotic STLV-1 transmission-defined as the product of prevalence in local NHP and human rates of contact to fresh NHP carcasses-contribute to the observed comparable rates of HTLV-1 infection in humans in CIV and DRC. We found that young adult men and mature women are most likely exposed to NHPs at both sites. In view of the continued difficulties in controlling zoonotic disease outbreaks, the identification of such groups at high risk of NHP exposure may guide future prevention efforts.IMPORTANCE Multiple studies report a high risk for zoonotic transmission of blood-borne pathogens like retroviruses through contact with NHPs, and this risk seems to be particularly high in tropical Africa. Here, we reveal high levels of exposure to NHP bushmeat in two regions of Western and Central tropical Africa. We provide evidence for continued zoonotic origin of HTLV-1 in humans at CIV, and we found that young men and mature women represent risk groups for zoonotic transmission of pathogens from NHPs. Identifying such risk groups can contribute to mitigation of not only zoonotic STLV-1 transmission but also transmission of any blood-borne pathogen onto humans in Sub-Saharan Africa.
Asunto(s)
Infecciones por Deltaretrovirus/transmisión , Infecciones por HTLV-I/epidemiología , Carne/virología , Primates/virología , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Zoonosis , Adulto , África Central , África del Norte/epidemiología , Animales , Animales Salvajes/virología , Côte d'Ivoire/epidemiología , Infecciones por Deltaretrovirus/epidemiología , Infecciones por Deltaretrovirus/prevención & control , Infecciones por Deltaretrovirus/virología , República Democrática del Congo/epidemiología , Brotes de Enfermedades/prevención & control , Femenino , Infecciones por HTLV-I/prevención & control , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Masculino , Filogenia , Prevalencia , Adulto Joven , Zoonosis/epidemiologíaRESUMEN
Specific pathogen free (SPF) macaques provide valuable animal models for biomedical research. In 1989, the National Center for Research Resources [now Office of Research Infrastructure Programs (ORIP)] of the National Institutes of Health initiated experimental research contracts to establish and maintain SPF colonies. The derivation and maintenance of SPF macaque colonies is a complex undertaking requiring knowledge of the biology of the agents for exclusion and normal physiology and behavior of macaques, application of the latest diagnostic technology, facilitiy management, and animal husbandry. This review provides information on the biology of the four viral agents targeted for exclusion in ORIP SPF macaque colonies, describes current state-of-the-art viral diagnostic algorithms, presents data from proficiency testing of diagnostic assays between laboratories at institutions participating in the ORIP SPF program, and outlines management strategies for maintaining the integrity of SPF colonies using results of diagnostic testing as a guide to decision making.
Asunto(s)
Macaca , Enfermedades de los Monos/diagnóstico , Virosis/veterinaria , Algoritmos , Animales , Betaretrovirus/aislamiento & purificación , Infecciones por Deltaretrovirus/diagnóstico , Infecciones por Deltaretrovirus/veterinaria , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/veterinaria , Herpesvirus Cercopitecino 1/aislamiento & purificación , Modelos Animales , Enfermedades de los Monos/virología , Control de Calidad , Infecciones por Retroviridae/diagnóstico , Infecciones por Retroviridae/veterinaria , Síndrome de Inmunodeficiencia Adquirida del Simio/diagnóstico , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Organismos Libres de Patógenos Específicos , Virosis/diagnósticoRESUMEN
Human T-cell leukemia virus type 1 (HTLV-1) is a delta-type retrovirus that induces malignant and inflammatory diseases during its long persistence in vivo. HTLV-1 can infect various kinds of cells; however, HTLV-1 provirus is predominantly found in peripheral CD4 T cells in vivo. Here we find that TCF1 and LEF1, two Wnt transcription factors that are specifically expressed in T cells, inhibit viral replication through antagonizing Tax functions. TCF1 and LEF1 can each interact with Tax and inhibit Tax-dependent viral expression and activation of NF-κB and AP-1. As a result, HTLV-1 replication is suppressed in the presence of either TCF1 or LEF1. On the other hand, T-cell activation suppresses the expression of both TCF1 and LEF1, and this suppression enables Tax to function as an activator. We analyzed the thymus of a simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaque, and found a negative correlation between proviral load and TCF1/LEF1 expression in various T-cell subsets, supporting the idea that TCF1 and LEF1 negatively regulate HTLV-1 replication and the proliferation of infected cells. Thus, this study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus.
Asunto(s)
Productos del Gen tax/antagonistas & inhibidores , Virus Linfotrópico T Tipo 1 Humano/fisiología , Factor de Unión 1 al Potenciador Linfoide/fisiología , Factor 1 de Transcripción de Linfocitos T/fisiología , Activación Transcripcional/fisiología , Animales , Línea Celular , Regulación hacia Abajo , Productos del Gen tax/fisiología , Humanos , Macaca , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Carga ViralRESUMEN
Simian T-cell lymphotropic viruses (STLV), the nonhuman primate counterparts of human T-cell lymphotropic viruses (HTLV), are endemic in many populations of African and Asian monkeys and apes. Although an etiologic link between STLV1 infection and lymphoproliferative disorders such as malignant lymphomas has been suggested in some nonhuman primate species, most STLV infections are inapparent, and infected animals remain clinically healthy. The retroviral transactivator, tax, is well known to increase transcription of viral and cellular genes, resulting in altered cytokine profiles. This study compared the cytokine profiles of peripheral blood mononuclear cell (PBMC) cultures from 25 STLV1-seropositive rhesus macaques (Macaca mulatta) with those of age- and sex-matched seronegative controls. IFNγ, TNFα, IL10, and IL2 levels in unstimulated PBMC culture supernatants were measured at 24, 48, and 72 h by using enzyme immunoassays. IFNγ concentrations were found significantly higher in the supernatants of PBMC cultures of seropositive monkeys as compared with seronegative controls. In addition, although IL2 concentrations were not significantly elevated in the supernatants of PBMC cultures of all seropositive monkeys as compared with all seronegative controls, IL2 levels were increased in a subset of 5 pairs. Increased constitutive cytokine release occurred in the absence of spontaneous proliferation. The increased constitutive release of IFNγ and IL2 suggests that STLV1 alters immune functions in infected but clinically healthy rhesus macaques and further characterizes STLV1 infection of rhesus macaques as a potential model for human HTLV1 infection.
Asunto(s)
Infecciones por Deltaretrovirus/sangre , Interferón gamma/sangre , Interleucina-2/sangre , Monocitos/metabolismo , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Animales , Células Cultivadas , Femenino , Macaca mulattaRESUMEN
Two young female baboons naturally infected with simian T-lymphotropic virus type 1 (STLV1) were euthanized due to chronic respiratory disease that was unresponsive to treatment. Massive lymphocytic infiltration of the lung interstitium suggested a diagnosis of STLV-associated lymphoma. In each case, the diagnosis was confirmed through inverse PCR (IPCR) that detected monoclonally integrated STLV1 provirus in cellular DNA extracted from lymphoma tissue and peripheral blood cells (PBC). One dominant STLV1-infected T-cell clone and 3 minor clones were detected in PBC from each baboon. Using archived PBC DNA and primers within the proviral genome and chromosomal DNA flanking the STLV1 integration sites in PCR analyses, we determined that the dominant clone in one baboon had first appeared approximately 8 mo after infection and had circulated for 4 y before clinical disease developed. ELISA testing of archived serum revealed that both baboons seroconverted to the p19 and p24 gag proteins and the envelope gp46 protein but not to the viral tax protein. Titers to p24 and gp46 rose significantly after infection and remained relatively constant until death, whereas titers to p19 increased with time. Although spontaneous STLV1-associated lymphomas have been described in baboons, the STLV1-associated lymphomas described here occurred in 2 relatively young baboons, both of whom had become infected with STLV at 3 to 4 y of age and developed lymphoma within 5 y of infection.
Asunto(s)
Linfoma/virología , Virus Linfotrópico T Tipo 1 de los Simios/patogenicidad , Animales , Secuencia de Bases , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Femenino , Genes Virales , Linfoma/inmunología , Papio , Reacción en Cadena de la Polimerasa/métodos , Virus Linfotrópico T Tipo 1 de los Simios/genética , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Carga ViralRESUMEN
Nonhuman primates are critical resources for biomedical research. Rhesus macaque is a popularly used laboratory nonhuman primate that share many characteristics with humans. However, rhesus macaques are the natural host of two exogenous retroviruses, SRV (simian type D retrovirus) and STLV (simian T lymphotropic virus). SRV and STLV may introduce potentially significant confounding factors into the study of AIDS model. Moreover, B virus (ceropithecine herpesvirus 1) is likely to harm not only rhesus macaque but also humans in experiments involving rhesus macaque. Yunnan province has large-scale breeding colonies of Chinese rhesus macaque. Therefore there is an urgent need for SPF Chinese rhesus macaque colonies. Here we investigated SRV, STLV and BV infections in 411 Chinese rhesus macaque by PCR technique. The results showed that the prevalence of SRV, STLV and BV among Chinese rhesus macaque breeding colony was 19.71% (81/411), 13.38% (55/411) and 23.11% (95/411), respectively. Comparison of viruses infection in different age-groups and male/female of Chinese rhesus macaque was also analyzed. This study will contribute to establishment of SPF Chinese rhesus macaque breeding colony.
Asunto(s)
Infecciones por Herpesviridae/veterinaria , Herpesvirus Cercopitecino 1/aislamiento & purificación , Macaca mulatta/virología , Enfermedades de los Primates/virología , Infecciones por Retroviridae/veterinaria , Retrovirus de los Simios/aislamiento & purificación , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Animales , Cruzamiento , China/epidemiología , Femenino , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Herpesvirus Cercopitecino 1/genética , Humanos , Macaca mulatta/genética , Masculino , Enfermedades de los Primates/epidemiología , Infecciones por Retroviridae/epidemiología , Infecciones por Retroviridae/virología , Retrovirus de los Simios/genética , Virus Linfotrópico T Tipo 1 de los Simios/genéticaRESUMEN
Serological inspection of Simian T-lymphotropic Virus Type 1 was conducted for a wild colony of Macaca fuscata, which was captured in the middle Honshu, Japan. The increase of positive rate after the juvenile stage with the positive rate reaching 100% (or 35/35) in youngster and adult stages, was observed. This finding suggests that, in contrast with human T-lymphotropic Virus Type 1, horizontal transmission play an important role in increasing prevalence of STLV-1 with age among M. fuscata.
Asunto(s)
Transmisión Vertical de Enfermedad Infecciosa , Síndrome de Inmunodeficiencia Adquirida del Simio/epidemiología , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Animales , Femenino , Macaca , Masculino , Embarazo , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisiónRESUMEN
Simian retroviruses are precursors of all human retroviral pathogens. However, little is known about the prevalence and coinfection rates or the genetic diversity of major retroviruses-simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus type 1 (STLV-1), and simian foamy virus (SFV)-in wild populations of nonhuman primates. Such information would contribute to the understanding of the natural history of retroviruses in various host species. Here, we estimate these parameters for wild West African red colobus monkeys (Piliocolobus badius badius) in the Taï National Park, Côte d'Ivoire. We collected samples from a total of 54 red colobus monkeys; samples consisted of blood and/or internal organs from 22 monkeys and additionally muscle and other tissue samples from another 32 monkeys. PCR analyses revealed a high prevalence of SIV, STLV-1, and SFV in this population, with rates of 82%, 50%, and 86%, respectively. Forty-five percent of the monkeys were coinfected with all three viruses while another 32% were coinfected with SIV in combination with either STLV or SFV. As expected, phylogenetic analyses showed a host-specific pattern for SIV and SFV strains. In contrast, STLV-1 strains appeared to be distributed in genetically distinct and distant clades, which are unique to the Taï forest and include strains previously described from wild chimpanzees in the same area. The high prevalence of all three retroviral infections in P. b. badius represents a source of infection to chimpanzees and possibly to humans, who hunt them.
Asunto(s)
Colobus/virología , Variación Genética , Enfermedades de los Monos/epidemiología , Infecciones por Retroviridae/veterinaria , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Virus Espumoso de los Simios/aislamiento & purificación , Animales , Análisis por Conglomerados , Comorbilidad , Côte d'Ivoire/epidemiología , Datos de Secuencia Molecular , Enfermedades de los Monos/virología , Filogenia , Prevalencia , Infecciones por Retroviridae/epidemiología , Infecciones por Retroviridae/virología , Análisis de Secuencia de ADN , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genética , Virus Linfotrópico T Tipo 1 de los Simios/clasificación , Virus Linfotrópico T Tipo 1 de los Simios/genética , Virus Espumoso de los Simios/clasificación , Virus Espumoso de los Simios/genéticaRESUMEN
Simian T-lymphotropic viruses type 1 (STLV-1) are regarded as a highly conserved group of viruses with genotypes clustering according to geographic regions rather than to infected species. In free living West African chimpanzees we have described a variety of STLV-1 strains and suggested that this diversity results from interspecies transmissions. Here we present new data on STLV-1 infections in these chimpanzees with the presence of two new distinct clades, proposing the establishing of two new STLV-1 subtypes. Moreover, in one of the chimpanzees, the Central African STLV-1 subtype B was detected. The STLV-1 strains detected here display a much wider diversity than heretofore reported for STLV-1 with presence of three distinct subtypes in chimpanzees from one distinct geographic region. In conclusion, the hypothesis of primate T-lymphotropic virus type 1 (PTLV-1) clustering by geography rather than host should be reconsidered, at least regarding STLV-1 infections in chimpanzees.
Asunto(s)
Enfermedades del Simio Antropoideo/virología , Infecciones por Deltaretrovirus/veterinaria , Pan troglodytes/virología , Polimorfismo Genético , ARN Viral/genética , Virus Linfotrópico T Tipo 1 de los Simios/clasificación , Virus Linfotrópico T Tipo 1 de los Simios/genética , Animales , Enfermedades del Simio Antropoideo/epidemiología , Análisis por Conglomerados , Côte d'Ivoire/epidemiología , Infecciones por Deltaretrovirus/epidemiología , Infecciones por Deltaretrovirus/virología , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Homología de Secuencia , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificaciónRESUMEN
A wild-born, 34-yr-old female western lowland gorilla (Gorilla gorilla gorilla) was transferred between zoologic collections in the United Kingdom. Adjustment to its new environment was difficult and a series of health problems ensued. Progressive severe illness of multiple etiologies, and a failure to respond to multiple therapies, led to its euthanasia 5 mo later. Disease processes included severe thoracic and axillary cutaneous ulceration of T2-3 dermatome distribution, gastroenteritis, ulcerative stomatitis, emaciation, hind limb weakness or paresis, and decubitus ulcers of the ankles and elbows. Ante- and postmortem infectious disease screening revealed that this animal was not infected with Mycobacterium tuberculosis, simian varicella virus (SVV), simian immunodeficiency virus (SIV), or hepatitis B virus; but was infected with varicella-zoster virus (VZV) and simian T-lymphotropic virus (STLV). It is hypothesized that recrudescence of VZV and other disease processes described were associated with chronic STLV infection and the end of a characteristically long incubation period.
Asunto(s)
Enfermedades del Simio Antropoideo/virología , Infecciones por Deltaretrovirus/veterinaria , Gorilla gorilla , Herpes Zóster/veterinaria , Herpesvirus Humano 3/aislamiento & purificación , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Animales , Enfermedad Crónica , Infecciones por Deltaretrovirus/virología , Femenino , Herpes Zóster/virologíaRESUMEN
OBJECTIVE: To assess the incidence of lymphoma and wasting-related deaths in the National Baboon Colony of Australia and relate it to the presence of simian T-cell lymphotrophic virus 1 (STLV-1) infection. DESIGN AND PROCEDURE: The records of all animals that had died since establishment of the National Baboon Colony in Australia were reviewed retrospectively. The clinical signs and histopathological findings were recorded and assessed to determine the involvement of lymphoma in the deaths. The presence of STLV-1 was recorded if known and correlated with the STLV-1 status of the colony. RESULTS: Of the deaths from disease or illness, 53% were diagnosed as or suspected to be lymphoma, occurring in mature animals with no sex predisposition. The most common presentation was rapidly occurring generalised lymphadenomegaly. CONCLUSIONS: This study has described a relatively high prevalence of lymphoma in a colony of captive-bred baboons, and it is evident that STLV-1 may play a role in the disease. Management practices in baboon colonies need to take into account the possible presence of STLV-1 and aim to reduce the transmission of the virus by preventing sexual contact between positive and negative animals. Lymphoma needs to be considered as one of the more common causes of wasting and death.
Asunto(s)
Infecciones por Deltaretrovirus/veterinaria , Linfoma/veterinaria , Enfermedades de los Monos/epidemiología , Papio hamadryas , Virus Linfotrópico T Tipo 1 de los Simios , Síndrome Debilitante/veterinaria , Animales , Australia/epidemiología , Infecciones por Deltaretrovirus/epidemiología , Infecciones por Deltaretrovirus/prevención & control , Ensayo de Inmunoadsorción Enzimática , Femenino , Incidencia , Linfoma/epidemiología , Linfoma/patología , Linfoma/virología , Masculino , Enfermedades de los Monos/patología , Enfermedades de los Monos/virología , Mortalidad , Estudios Retrospectivos , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Síndrome Debilitante/epidemiología , Síndrome Debilitante/virologíaRESUMEN
A single-tube, multiplex, real-time PCR assay with molecular beacons was established in which various probes were used for the simultaneous detection, differentiation, and quantification of human T-cell leukemia virus types 1, 2, and 3 (HTLV-1, HTLV-2, and HTLV-3, respectively) and of simian T-cell leukemia virus types 1 and 3 (STLV-1 and STLV-3, respectively). The quantitative amplification of the standards with MT4 (HTLV-1) and C19 (HTLV-2) cell lines and a molecular clone of HTLV-3 was linear, with the simplex and multiplex methods having similar efficiencies. A maximum difference of 0.9 (mean, 0.4; range, 0.0 to 0.9) was found between threshold cycle values in single and multiplex reactions. The efficiency with each probe in the multiplex reaction was close to 100%, indicating strong linear amplification. The albumin gene was used to standardize the copy number. Comparable results for the detection and quantification of HTLV-1 were obtained with our new methods and with other real-time PCR methods described previously. With our new multiplex assay, however, we were able to detect and quantify HTLV-2 and -3 and STLV-1 and -3 in clinical specimens, with an excellent dynamic range of 10(6) to 10(0) copies per assay, which the other assays could not do. Thus, it will be possible to determine a wide range of HTLV types in both standard and clinical samples, with a detection of 1 to 10 HTLV copies in samples containing at least 100 cells. Furthermore, our system can provide evidence for multiple infections with the three HTLV types, with separate proviral load results. Our new method also could be used for epidemiological studies in Africa and in countries where HTLVs and STLVs are endemic.
Asunto(s)
Infecciones por Deltaretrovirus/diagnóstico , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Virus Linfotrópico T Tipo 2 Humano/aislamiento & purificación , Sondas de Oligonucleótidos/genética , Reacción en Cadena de la Polimerasa/métodos , Virus Linfotrópico T Tipo 3 de los Primates/aislamiento & purificación , Infecciones Tumorales por Virus/diagnóstico , África , Sangre/virología , Infecciones por Deltaretrovirus/virología , Femenino , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 2 Humano/genética , Humanos , Reacción en Cadena de la Polimerasa/normas , Embarazo , Virus Linfotrópico T Tipo 3 de los Primates/genética , Sensibilidad y Especificidad , Virus Linfotrópico T Tipo 1 de los Simios/genética , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Infecciones Tumorales por Virus/virologíaRESUMEN
Cross-species transmission of retroviruses is common in Cameroon. To determine risk for simian T-cell lymphotropic virus (STLV) transmission from nonhuman primates to hunters, we examined 170 hunter-collected dried blood spots (DBS) from 12 species for STLV. PCR with generic tax and group-specific long terminal repeat primers showed that 12 (7%) specimens from 4 nonhuman primate species were infected with STLV. Phylogenetic analyses showed broad diversity of STLV, including novel STLV-1 and STLV-3 sequences and a highly divergent STLV-3 subtype found in Cercopithecus mona and C. nictitans monkeys. Screening of peripheral blood mononuclear cell DNA from 63 HTLV-seroreactive, PCR-negative hunters did not identify human infections with this divergent STLV-3. Therefore, hunter-collected DBS can effectively capture STLV diversity at the point where pathogen spillover occurs. Broad screening using this relatively easy collection strategy has potential for large-scale monitoring of retrovirus cross-species transmission among highly exposed human populations.
Asunto(s)
Animales Salvajes/virología , Cercopithecidae/virología , Infecciones por Deltaretrovirus/veterinaria , Variación Genética , Virus Linfotrópico T Tipo 3 de los Primates/clasificación , Virus Linfotrópico T Tipo 1 de los Simios/clasificación , Strepsirhini/virología , Animales , Animales Salvajes/clasificación , Recolección de Muestras de Sangre/métodos , Camerún/epidemiología , Cercopithecidae/clasificación , Infecciones por Deltaretrovirus/epidemiología , Infecciones por Deltaretrovirus/virología , Humanos , Carne/virología , Enfermedades de los Monos/epidemiología , Enfermedades de los Monos/virología , Reacción en Cadena de la Polimerasa , Virus Linfotrópico T Tipo 3 de los Primates/genética , Virus Linfotrópico T Tipo 3 de los Primates/aislamiento & purificación , Análisis de Secuencia de ADN , Virus Linfotrópico T Tipo 1 de los Simios/genética , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Strepsirhini/clasificaciónRESUMEN
The molecular identification of proviruses from ancient tissues (and particularly from bones) remains a contentious issue. It can be expected that the copy number of proviruses will be low, which magnifies the risk of contamination with retroviruses from exogenous sources. To assess the feasibility of paleoretrovirological studies, we attempted to identify proviruses from early 20th century bones of museum specimens while following a strict ancient DNA methodology. Simian T-cell leukemia virus type 1 sequences were successfully obtained and authenticated from a Chlorocebus pygerythrus specimen. This represents the first clear evidence that it will be possible to use museum specimens to better characterize simian and human T-tropic retrovirus genetic diversity and analyze their origin and evolution, in greater detail.
Asunto(s)
Cercopithecinae/virología , ADN Viral/aislamiento & purificación , Evolución Molecular , Variación Genética , Provirus/aislamiento & purificación , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Animales , ADN Viral/genética , ADN Viral/historia , Historia del Siglo XX , Filogenia , Provirus/clasificación , Provirus/genética , Virus Linfotrópico T Tipo 1 de los Simios/clasificación , Virus Linfotrópico T Tipo 1 de los Simios/genética , Secuencias Repetidas TerminalesRESUMEN
Humans and simian species are infected by deltaretroviruses (HTLV and STLV respectively), which are collectively called primate T-cell lymphotropic viruses (PTLVs). In humans, four types of HTLV have been described (HTLV-1 to -4) with three of them having closely related simian virus analogues named STLV-1, 2 and 3. In this study, our aim was to search for a simian HTLV-4-related virus and to document and characterize further the diversity of STLV infections in wild primate populations. We screened 1297 whole blood samples from 13 different primate species from southern Cameroon. Overall, 93 samples gave HTLV-1, HTLV-2 or dual HTLV-1/-2 INNOLIA profiles, 12 were HTLV positive but untypeable and 14 were indeterminate. Subsequently, we performed generic and specific (STLV-1 to -3) tax-rex PCRs to discriminate the different PTLV types, completed with phylogenetic analysis of 450-bp LTR sequences for STLV-1 and 900 bp pX-LTR sequences for STLV-3. We show for the first time that Lophocebus albigena and Cercopithecus cephus carry both STLV-1 and a divergent STLV-3. We also identified a new STLV-1 lineage in one C. cephus. Finally, we identify relative divergence levels in the tax/rex phylogeny suggesting that additional types of PTLV should be defined, particularly for the highly divergent STLV-1(MarB43) strain that we provisionally name STLV-5.
Asunto(s)
Animales Salvajes/virología , Enfermedades del Simio Antropoideo/virología , Infecciones por Deltaretrovirus/veterinaria , Enfermedades de los Monos/virología , Virus Linfotrópico T Tipo 3 de los Primates/clasificación , Virus Linfotrópico T Tipo 1 de los Simios/clasificación , Animales , Anticuerpos Antivirales/sangre , Enfermedades del Simio Antropoideo/epidemiología , Camerún , Cercocebus , Infecciones por Deltaretrovirus/epidemiología , Infecciones por Deltaretrovirus/virología , Variación Genética , Gorilla gorilla , Haplorrinos , Datos de Secuencia Molecular , Enfermedades de los Monos/epidemiología , Filogenia , Virus Linfotrópico T Tipo 3 de los Primates/genética , Virus Linfotrópico T Tipo 3 de los Primates/inmunología , Virus Linfotrópico T Tipo 3 de los Primates/aislamiento & purificación , Análisis de Secuencia de ADN , Virus Linfotrópico T Tipo 1 de los Simios/genética , Virus Linfotrópico T Tipo 1 de los Simios/inmunología , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Secuencias Repetidas Terminales/genéticaRESUMEN
Immunophenotyping of cultured continuous simian lymphoid cultures using a panel containing monoclonal antibodies to human B- and T-cell antigens has been carried out, by employing enzyme immunoassay and flow cytofluorometry. The test cultures showed a wide variety of cells containing B- and T-cell antigens with their varying expression. The cultures were also found to comprise lymphoblasts simultaneously containing B- and T-cell markers. Simian lymphotropic viruses, such as EBV-like and STLV-1 retrovirus, detected apart or simultaneously, have been verified by polymerase chain reaction. Whether there is a possible relationship between the type of cells in the culture and the type of their replicating virus(es) is discussed in the paper.