RESUMEN
OBJECTIVES: Human herpesvirus 8 (HHV8) is rarely studied in Congo, despite its prevalence in Africa. Among healthy individuals, HHV-8 does not always lead to a life-threatening infection; however, in immunocompromised individuals, it could lead to more severe disease. The distribution of HHV-8 genotypes varies depending on ethnicity and geographic region. METHOD: A prospective cross-sectional study included 265 samples from healthy blood donors from the National Blood Transfusion Center in Brazzaville, with an average age of 35 years, with extremes ranging from 18 to 60 years. After DNA extraction, a nested PCR was carried out for molecular detection, followed by genotyping by amplification of specific primers. RESULT: In this study, 4.9% were positive for molecular detection of HHV-8 DNA. All HHV-8 positive DNA samples that were subjected to genotyping by amplification with specific primers allowing discrimination of two major genotypes (A and B). Genotype A was identified in 5 (1.9%) samples and genotype B in 2 (0.7%) samples, indicating that both genotypes were predominant. The remaining viral DNA samples not identified as the major genotypes were classified as «indeterminate¼ and consisted of 6 (2.3%) samples. CONCLUSION: The results of the study suggest that Congo is an area where HHV-8 infection is endemic.
Asunto(s)
Donantes de Sangre , ADN Viral , Genotipo , Infecciones por Herpesviridae , Herpesvirus Humano 8 , Humanos , Congo/epidemiología , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/aislamiento & purificación , Herpesvirus Humano 8/clasificación , Adulto , Masculino , Femenino , Persona de Mediana Edad , ADN Viral/genética , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/sangre , Adolescente , Estudios Transversales , Estudios Prospectivos , Reacción en Cadena de la PolimerasaRESUMEN
Human Herpesvirus 8 (HHV-8) has been classified by sequence analysis of open reading frame (ORF) K1, ORF K15, and variable sequence loci within the central constant region. The purpose of this study was to examine the molecular epidemiology of HHV-8 in an Irish population. This retrospective study included 30 patients who had HHV-8 DNA detected in plasma. Nested end-point PCR was used to characterise four regions of the HHV-8 genome, K1, T0.7 (K12), ORF 75, and K15. Sequencing data were obtained for 23 specimens from 19 patients. Phylogenetic analysis of ORF K1 demonstrated that subtypes A, B, C and F were present in 37%, 11%, 47% and 5%, respectively. For T0.7 and ORF 75, sequencing data were obtained for 12 patients. For T0.7, subtypes A/C, J, B, R and Q were present in 58%, 17%, 8%, 8%, and 8%, respectively. For ORF 75, subtypes A, B, C and D were present in 58%, 8%, 25%, and 8%, respectively. K15 sequences were determined for 13 patients. 69% had the P allele and 31% had the M allele. The data generated by this study demonstrate that a broad variety of HHV-8 subtypes are represented in patients exhibiting HHV-8-related disease in Ireland, a low prevalence country. The predominance of C and A K1 subtypes was as expected for a Western European population. The 31% prevalence for K15 subtype M was higher than expected for a Western European population. This may represent the changing and evolving epidemiology in Ireland due to altered migration patterns.
Asunto(s)
ADN Viral , Infecciones por Herpesviridae , Herpesvirus Humano 8 , Epidemiología Molecular , Filogenia , Análisis de Secuencia de ADN , Humanos , Irlanda/epidemiología , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/aislamiento & purificación , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , ADN Viral/genética , Anciano , Adulto Joven , Reacción en Cadena de la Polimerasa , Genotipo , Adolescente , Sistemas de Lectura Abierta , Anciano de 80 o más Años , Niño , Datos de Secuencia MolecularRESUMEN
Kaposi sarcoma (KS)-associated herpesvirus (KSHV/HHV-8) was first sequenced from the body cavity (BC) lymphoma cell line, BC-1, in 1996. Few other KSHV genomes have been reported. Our knowledge of sequence variation for this virus remains spotty. This study reports additional genomes from historical US patient samples and from African KS biopsies. It describes an assay that spans regions of the virus that cannot be covered by short read sequencing. These include the terminal repeats, the LANA repeats, and the origins of replication. A phylogenetic analysis, based on 107 genomes, identified three distinct clades; one containing isolates from USA/Europe/Japan collected in the 1990s and two of Sub-Saharan Africa isolates collected since 2010. This analysis indicates that the KSHV strains circulating today differ from the isolates collected at the height of the AIDS epidemic. This analysis helps experimental designs and potential vaccine studies.
Asunto(s)
Genoma Viral , Genómica , Genotipo , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Sarcoma de Kaposi/virología , Adulto , Línea Celular , Femenino , Regulación Viral de la Expresión Génica , Genómica/métodos , Infecciones por Herpesviridae/diagnóstico , Herpesvirus Humano 8/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Filogenia , Recombinación GenéticaRESUMEN
Human herpesvirus 8 (HHV8) is endemic in Africa, although studies of this infection are rare in Congo. We evaluated seroprevalence and HHV-8 diversity among people living with HIV. We included 353 patients receiving highly active antiretroviral therapy. Antibodies against HHV-8 latency-associated nuclear antigen were detected by indirect immunofluorescence. In HHV-8 positive patients, we performed HHV-8 quantification in blood and saliva by real-time PCR and typing by Sanger sequencing of K1 open reading frame. HHV-8 seroprevalence was 19%, being male (odd ratio [OR] = 1.741, [95% Confidence interval {CI}, 0.97-3.07]; p = 0.0581) and having multiple sex partners before HIV diagnosis (OR = 1.682, [CI 95%, 0.97-2.92]; p = 0.0629) tended to be associated with HHV-8 seropositivity. Of the 64 HHV-8 seropositive patients, HHV-8 DNA was detected in 10 (16%) in saliva, 6 (9%) in whole-blood and in 2 (3%) in both whole-blood and saliva. Three out of 6 HHV-8 strains were subtypes A5, 2 subtype B1 and 1 subtype C. HHV-8 seroprevalence was relatively low with more frequent carriage in men, associated with asymptomatic oral excretion and a predominance of subtype A5. These data tend to support the hypothesis of horizontal transmission in people living with HIV in Brazzaville.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por VIH/complicaciones , VIH/aislamiento & purificación , Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8/clasificación , Saliva/virología , Adulto , África/epidemiología , Estudios Transversales , Femenino , Estudios de Seguimiento , Infecciones por VIH/virología , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/inmunología , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Pronóstico , Estudios Prospectivos , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: Classic Kaposi sarcoma (CKS) is a vascular sarcoma associated with human herpesvirus 8 (HHV-8), which is known to be more common in Mediterranean elderly men and is characterized by indolent clinical behavior. Xinjiang province in China is considered an endemic region for Kaposi's sarcoma-associated herpesvirus (KSHV), with higher incidence among adults of Kazak and Uyghur ethnicities. Cases of CKS are rarely reported in inland China. Here, we followed a case of CKS for 7 years in a patient of Miao ethnic background in southwestern China. CASE PRESENTATION: A 63-year-old Miao (southwestern China) man was initially diagnosed with CKS in 2010, having a history of limb lesions for 37 years, with left eyelid and binaural lesions for 9 years. He did not have sexual contact with men and was human immunodeficiency virus (HIV)-negative. Due to his lumbago and fever, spinal tuberculosis in the lumbar vertebra was highly suspected after computed tomography (CT) scan. However, diagnostic antituberculosis treatment for 4 weeks failed. The patient was followed up in 2016, when the rash was recovering as the systemic symptoms improved. A new CT was performed, which showed a partial response despite the absence of any medical treatment. The open reading frame (ORF)-K1 of KSHV from skin tissue of the foot was amplified and sequenced, and K1 belonged to subtype A. This genotype is consistent with the typical subtype present in Xinjiang. CONCLUSIONS: We describe spontaneous partial regression of CKS in a patient of Miao ethnicity in inland China. Our sample may represent an unknown, novel genotype. Surveillance and regulating the immune state may represent a valuable approach for this rare disease.
Asunto(s)
Herpesvirus Humano 8/genética , Herpesvirus Humano 8/aislamiento & purificación , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , China , Etnicidad , Genoma Viral , Genotipo , Herpesvirus Humano 8/clasificación , Humanos , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Sarcoma de Kaposi/virología , Neoplasias Cutáneas/virología , Proteínas del Envoltorio Viral/clasificación , Proteínas del Envoltorio Viral/genéticaRESUMEN
Human herpesvirus 8 (HHV-8) is the etiological agent of all forms of Kaposi's sarcoma (KS). K1 gene studies have identified five major molecular genotypes with geographical clustering. This study described the epidemiology of HHV-8 and its molecular diversity in Gabon among Bantu and Pygmy adult rural populations and KS patients. Plasma antibodies against latency-associated nuclear antigens (LANA) were searched by indirect immunofluorescence. Buffy coat DNA samples were subjected to polymerase chain reaction (PCR) to obtain a K1 gene fragment. We studied 1020 persons; 91% were Bantus and 9% Pygmies. HHV-8 seroprevalence was 48.3% and 36.5% at the 1:40 and 1:160 dilution thresholds, respectively, although the seroprevalence of HHV-8 is probably higher in Gabon. These seroprevalences did not differ by sex, age, ethnicity or province. The detection rate of HHV-8 K1 sequence was 2.6% by PCR. Most of the 31 HHV-8 strains belonged to the B genotype (24), while the remaining clustered within the A5 subgroup (6) and one belonged to the F genotype. Additionally, we reviewed the K1 molecular diversity of published HHV-8 strains in Africa. This study demonstrated a high seroprevalence of HHV-8 in rural adult populations in Gabon and the presence of genetically diverse strains with B, A and also F genotypes.
Asunto(s)
Herpesvirus Humano 8/genética , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , ADN Viral/genética , Femenino , Gabón/epidemiología , Variación Genética , Genotipo , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/inmunología , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/inmunología , Filogenia , Población Rural , Estudios Seroepidemiológicos , Proteínas Virales/genética , Adulto JovenRESUMEN
Intra-host tumor virus variants may influence the pathogenesis and treatment responses of some virally-associated cancers. However, the intra-host variability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma (KS), has to date been explored with sequencing technologies that possibly introduce more errors than that which occurs in the viral population, and these studies have only studied variable regions. Here, full-length KSHV genomes in tumors and/or oral swabs from 9 Ugandan adults with HIV-associated KS were characterized. Furthermore, we used deep, short-read sequencing using duplex unique molecular identifiers (dUMI)-random double-stranded oligonucleotides that barcode individual DNA molecules before library amplification. This allowed suppression of PCR and sequencing errors to ~10-9/base as well as afforded accurate determination of KSHV genome numbers sequenced in each sample. KSHV genomes were assembled de novo, and rearrangements observed were confirmed by PCR and Sanger sequencing. 131-kb KSHV genome sequences, excluding major repeat regions, were successfully obtained from 23 clinical specimens, averaging 2.3x104 reads/base. Strikingly, KSHV genomes were virtually identical within individuals at the point mutational level. The intra-host heterogeneity that was observed was confined to tumor-associated KSHV mutations and genome rearrangements, all impacting protein-coding sequences. Although it is unclear whether these changes were important to tumorigenesis or occurred as a result of genomic instability in tumors, similar changes were observed across individuals. These included inactivation of the K8.1 gene in tumors of 3 individuals and retention of a region around the first major internal repeat (IR1) in all instances of genomic deletions and rearrangements. Notably, the same breakpoint junctions were found in distinct tumors within single individuals, suggesting metastatic spread of rearranged KSHV genomes. These findings define KSHV intra-host heterogeneity in vivo with greater precision than has been possible in the past and suggest the possibility that aberrant KSHV genomes may contribute to aspects of KS tumorigenesis. Furthermore, study of KSHV with use of dUMI provides a proof of concept for utilizing this technique for detailed study of other virus populations in vivo.
Asunto(s)
ADN Viral/análisis , Genoma Viral , Herpesvirus Humano 8/genética , Especificidad del Huésped , Sarcoma de Kaposi/virología , Adulto , Estudios de Cohortes , ADN Viral/genética , Femenino , Genómica , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Sarcoma de Kaposi/epidemiología , Uganda/epidemiologíaRESUMEN
BACKGROUND: Kaposi sarcoma (KS)-associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex with men (MSM) living in France. METHODS: The study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)-infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant. RESULTS: We found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups. CONCLUSIONS: Subtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.
Asunto(s)
Herpesvirus Humano 8/genética , Sarcoma de Kaposi/patología , Sarcoma de Kaposi/virología , Adulto , ADN Viral/genética , Francia/epidemiología , Variación Genética , Genoma Viral/genética , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/aislamiento & purificación , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Prevalencia , Estudios Retrospectivos , Sarcoma de Kaposi/epidemiología , Minorías Sexuales y de Género , Proteínas Virales/genéticaRESUMEN
Variations in the open reading frame (ORF) K1 gene sequence of human gammaherpesvirus 8 (HHV-8) has led to the identification of 6 major genotypic clades (A, B, C, D, E, and F) in specimens isolated from around the world. These clades exhibit clear clustering among individuals in different ethnic groups and from different geographic regions. The human population of Brazil varies greatly in ethnicity because of multiple immigration events from Africa, Europe, Asia, and indigenous communities. However, there is scant information about the HHV-8 genotypes currently circulating in Brazil. Here, we describe HHV-8 genotypic diversity in isolates from Brazilian HIV-infected patients living with Kaposi's sarcoma (KS) by analysis of the complete ORF-K1 region. We also identified the most likely geographic origins of these different Brazilian genotypes. We extracted HHV-8 DNA (24 positive samples) from individuals with HIV/KS from the states of São Paulo and Rio de Janeiro, amplified the ORF-K1 gene using nested PCR (about 870 base pairs), performed sequencing and phylogenetic analysis, and then calculated the mean genetic distances of Brazilian sequences from sequences in other regions of the world (523 sequences analyzed). Phylogenetic analysis showed that genotypes C, A, and B were present in 45.8 %, 29.2 % and 25 % of the isolates from Brazil, respectively. These isolates grouped into separate clades, rather than a single monophyletic cluster. Mean genetic distance analyses suggested that these genotypes were introduced into the Brazil multiple times from different geographical regions. HHV-8/A isolates appear to be from Ukraine, Russia, and the Tartar ethnic group; HHV-8/B isolates appear to be from Congo and Democratic Republic of the Congo; and HHV-8/C isolates appear to be from Australia, Algeria, England, and French Guiana. These results contribute to a better understanding of the genetic diversity and origins of HHV-8 strains circulating in Brazil, and will provide a foundation for further epidemiological and evolutionary studies of HHV-8.
Asunto(s)
Variación Genética , Genotipo , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Adulto , Brasil/epidemiología , Enfermedades Transmisibles Importadas/epidemiología , Enfermedades Transmisibles Importadas/virología , Femenino , Geografía , Infecciones por VIH/virología , Infecciones por Herpesviridae/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Estudios Retrospectivos , Saliva/virología , Sarcoma de Kaposi/virología , Análisis de Secuencia de ADN , Adulto JovenAsunto(s)
Herpesvirus Humano 8/clasificación , Homosexualidad Masculina , Filogenia , Abuso de Sustancias por Vía Intravenosa/sangre , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Secuencia de Bases , Recuento de Linfocito CD4 , Femenino , Variación Genética , Herpesvirus Humano 8/genética , Humanos , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Abuso de Sustancias por Vía Intravenosa/inmunología , Abuso de Sustancias por Vía Intravenosa/virología , Taiwán/epidemiología , Carga Viral , Adulto JovenRESUMEN
KSHV-associated inflammatory cytokine syndrome (KICS) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). KICS is associated with high-level, systemic replication of KSHV. This study characterized the clinical and virologic features of a KICS patient over time. Additionally, it compared the cytokine profiles of the KICS case to Kaposi's sarcoma (KS) (nâ¯=â¯11) and non-KS (nâ¯=â¯6) cases. This KICS case presented with elevated levels of KSHV and IL-10, as expected. Surprisingly, this case did not have elevated levels of IL-6 or human immunodeficiency virus 1 (HIV-1). Nevertheless, treatment with anti-IL6 receptor antibody (tocilizumab) reduced KSHV viral load and IL-10. The KSHV genome sequence showed no significant changes over time, except in ORF24. Phylogenetic analysis established this isolate as belonging to KSHV clade A and closely related to other US isolates. These findings suggest IL-10 as potential biomarker and therapy target for KICS.
Asunto(s)
Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/fisiología , Interleucina-10/sangre , Replicación Viral/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores/sangre , Síndrome de Liberación de Citoquinas , ADN Viral/sangre , ADN Viral/genética , Genoma Viral/genética , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/tratamiento farmacológico , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Filogenia , Sarcoma de Kaposi/inmunología , Sarcoma de Kaposi/virología , Carga ViralRESUMEN
We determined the complete genome sequence of a virus isolated from a mantled guereza that died of primary effusion lymphoma. The virus is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV) but lacks some genes implicated in KSHV pathogenesis. This finding may help determine how KSHV causes primary effusion lymphoma in humans.
Asunto(s)
Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Linfoma/veterinaria , Enfermedades de los Monos/diagnóstico , Enfermedades de los Monos/virología , Animales , Biopsia , Colobus , Genoma Viral , Genómica , Herpesvirus Humano 8/aislamiento & purificación , Inmunohistoquímica , Masculino , Enfermedades de los Monos/epidemiología , Filogenia , Secuenciación Completa del GenomaRESUMEN
HHV-8 genotypes are distributed heterogeneously worldwide. The variable K1 gene and the conserved ORF26E region serve to genotype. The aim of the study was to characterize HHV-8 isolates from patients with AIDS, classical, and iatrogenic KS, primary effusion lymphoma and Castleman's disease and one organ donor from Argentina by analysis of ORFK1 and ORF26E regions. DNA was extracted from fresh or paraffin embedded biopsies, blood, and saliva samples and submitted to HHV-8 PCR. Phylogenetic analyses of ORFK1 showed that subtypes C (C1, C2, and C3), B1 and A (A1, A2, and A3) were present in 70.8%, 16.7%, and 12.5% of cases, respectively. Analyses of ORF26E fragment revealed that most strains (45.8%) were subtype A/C while the remaining fall into K, J, B2, R, and D subtypes. Linkage between ORFK1-ORF26E subtypes corresponded to reported relationships, except for one strain that clustered with B1 (K1 African) and D (ORF26E Asian-Pacific) subtypes. This research reveals predominance of subtype C, a broad spectrum of HHV-8 genotypes and reports the first isolation of the African B genotype in Argentina.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/virología , Enfermedad de Castleman/virología , Variación Genética , Herpesvirus Humano 8/genética , Linfoma de Efusión Primaria/virología , Sarcoma de Kaposi/virología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Adulto , Anciano , Argentina/epidemiología , Enfermedad de Castleman/epidemiología , ADN Viral/genética , Evolución Molecular , Femenino , Genotipo , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Linfoma de Efusión Primaria/epidemiología , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa , Saliva/virología , Sarcoma de Kaposi/sangre , Sarcoma de Kaposi/epidemiología , Donantes de TejidosRESUMEN
It is still unclear whether different HHV-8 genotypes may have different pathogenic and tumorigenic properties associated with a diverse rate of disease progression. In some areas where genotype C was found to be prominent among classic KS patients, genotype A was shown to be more frequent among AIDS-associated KS patients. Genotype C was previously reported to be widespread in Iran, with genotype A being less frequent among patients with classic KS although no data are available with regards to the HHV-8 genotyping among Iranian HIV-infected patients. In order to analyze HHV-8 genotypes (ORF K1), six HIV-infected patients (with or without KS), and 22 HIV-negative subjects (classic/iatrogenic KS patients and IVDUs) were investigated using nested PCR. Genotype A was detected more frequently among HIV-infected patients with or without KS (three out of six) whereas genotype C was found more common among HIV-negative subjects including classic/iatrogenic KS patients and IVDSs (21 out of 22), and this difference was statistically significant (P = 0.044). In conclusion, our data further support the dominancy of HHV-8 genotype C in Iranian general population. Moreover, genotype A was more common among HIV-infected patients with or without KS. J. Med. Virol. 89:703-709, 2017. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Genotipo , Infecciones por VIH/complicaciones , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Tipificación Molecular , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Técnicas de Genotipaje , Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Reacción en Cadena de la PolimerasaRESUMEN
The prevalence of Human Herpesvirus 8 (HHV8) DNA and antiviral antibodies in Diabetes type 2 (DM2) and control subjects was studied, in order to confirm a possible link between DM2 and HHV8 infection. The HHV8-DNA from diabetic patients was typed for detecting possible genomic differences with known HHV8 reference viruses.DM2 patients and healthy controls were examined for the presence of HHV8 DNA into the peripheral blood lymphocytes. Both anti-lytic and latent phase antibodies were detected in HHV8 positive and negative diabetic patients, as well in a number of controls. The HHV8 ORF K1 and ORF 26 genes from DM2 patients were typed and matched to reference strains.A significant prevalence of HHV8 DNA in DM2 subjects versus healthy controls was detected (about 58 % against 27 %). Anti-lytic phase, but not anti-latent phase antibodies, were significantly increased in DM2 patients versus controls. In addition, about 30 % of HHV8 strains isolated from DM2 lymphocytes showed consistent differences in the ORF 26 gene sequence, so that a new HHV8 subtype was proposed. These findings give additional support to the hypothesis that HHV8 could be considered an additional risk factor for DM2 onset.
Asunto(s)
Diabetes Mellitus Tipo 2/virología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/aislamiento & purificación , Anciano , Femenino , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Humanos , Masculino , Persona de Mediana Edad , FilogeniaRESUMEN
The envelope-associated glycoprotein B (gB) is highly conserved within the Herpesviridae and plays a critical role in viral entry. We analyzed the evolutionary conservation of sequence and structural motifs within the Kaposi׳s sarcoma-associated herpesvirus (KSHV) gB and homologs of Old World primate rhadinoviruses belonging to the distinct RV1 and RV2 rhadinovirus lineages. In addition to gB homologs of rhadinoviruses infecting the pig-tailed and rhesus macaques, we cloned and sequenced gB homologs of RV1 and RV2 rhadinoviruses infecting chimpanzees. A structural model of the KSHV gB was determined, and functional motifs and sequence variants were mapped to the model structure. Conserved domains and motifs were identified, including an "RGD" motif that plays a critical role in KSHV binding and entry through the cellular integrin αVß3. The RGD motif was only detected in RV1 rhadinoviruses suggesting an important difference in cell tropism between the two rhadinovirus lineages.
Asunto(s)
Secuencia Conservada , Evolución Molecular , Herpesvirus Humano 8/genética , Rhadinovirus/genética , Proteínas del Envoltorio Viral/genética , Secuencias de Aminoácidos , Animales , Secuencia de Bases , Variación Genética , Genoma Viral , Herpesvirus Humano 8/clasificación , Humanos , Macaca mulatta , Modelos Moleculares , Pan troglodytes , Filogenia , Regiones Promotoras Genéticas , Dominios y Motivos de Interacción de Proteínas , Estructura Secundaria de Proteína , Rhadinovirus/clasificación , Análisis de Secuencia de ADN , Homología de Secuencia , Relación Estructura-Actividad , Proteínas del Envoltorio Viral/químicaRESUMEN
Human herpes virus 8 (HHV8) is the etiological agent of all forms of Kaposi's sarcoma (KS). Six major subtypes (A-F), based on genetic variability of open reading frame (ORF)-K1, have been identified. Numerous studies point to differing tumorigenic and pathogenic properties of the HHV8 subtypes. The study objectives were to determine the HHV8 subtypes and their prevalence in a cohort of clinical and histologically confirmed KS in Cape Town, South Africa, and analyze associations between the different subtypes and clinical presentation of KS. Clinical records were prospectively reviewed to extract clinical presentation; demographic data were retrospectively collected and tissue biopsies were taken for ORF-K1 subtyping. Eighty six patients were subtyped; 81 AIDS (acquired immune deficiency syndrome)-KS and 5 African endemic-KS. Subtype A5 (42/86) and B2 (16/86) predominated. B1, B3, A1 and A4 subtypes were identified in 10/86, 9/86, 4/86 and 1/86 patients, respectively. A5 and B subtypes were found in African blacks and individuals of mixed ancestry, while subtypes A1 and A4 were found only in whites and individuals of mixed ancestry. Subtype A5 was associated with >10 KS lesions at presentation in the AIDS cohort (adjusted OR: 3.13; CI: 1.02-9.58). Subtypes A1 and A4 combined were less likely to be associated with poor risk tumor extension (P = 0.031) and A1 was associated with lower likelihood of lower limb involvement (P = 0.019). In conclusion, these results indicate that subtype A5 and B predominate in South Africa and A5 may be associated with more extensive disease.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Variación Genética , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/virología , Síndrome de Inmunodeficiencia Adquirida/patología , Adulto , Femenino , Genotipo , Herpesvirus Humano 8/aislamiento & purificación , Humanos , Masculino , Epidemiología Molecular , Prevalencia , Estudios Retrospectivos , Sarcoma de Kaposi/patología , Sudáfrica/epidemiologíaRESUMEN
Blood samples were collected from 101 untreated pulmonary tuberculosis (TB) patients and 101 age- and sex-matched healthy control subjects. TB patients had lower lymphocyte and a higher monocyte counts than control subjects (p <0.0001 for both). The seropositive rate of human herpesvirus (HHV) type 8 antibody was higher in patients (30/101) than in control subjects (15/101) (p = 0.01). Antibody titres in patients also exceeded those in control subjects (p 0.006). Lymphocyte and monocyte counts between seronegative and seropositive subjects were not different. Four patients were positive for HHV-8 DNA. The study revealed a significantly higher HHV-8 seroprevalence in untreated pulmonary TB patients than in general population.
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Coinfección , Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8 , Tuberculosis Pulmonar/epidemiología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Estudios de Casos y Controles , Femenino , Infecciones por Herpesviridae/inmunología , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/inmunología , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Prevalencia , Sarcoma de Kaposi/epidemiología , Sarcoma de Kaposi/inmunología , Estudios Seroepidemiológicos , Taiwán/epidemiología , Tuberculosis Pulmonar/inmunologíaRESUMEN
BACKGROUND: Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with cKS or in HHV-8 infected subjects either asymptomatic or with cKS-unrelated cutaneous lymphoproliferative disorders. METHODS: The VR1 and VR2 regions of the ORF K1 sequence were analyzed in samples (peripheral blood and/or lesional tissue) collected between 2000 and 2010 from 27 subjects with HHV-8 infection, established by the presence of anti-HHV-8 antibodies. On the basis of viral genotyping, a phylogenetic analysis and a time-scaled evaluation were performed. RESULTS: Two main clades of HHV-8, corresponding to A and C subtypes, were identified. Moreover, for each subtype, two main clusters were found distinctively associated to cKS or non-cKS subjects. Selective pressure analysis showed twelve sites of the K1 coding gene (VR1 and VR2 regions) under positive selective pressure and one site under negative pressure. CONCLUSION: Thus, present data suggest that HHV-8 genetic variants may influence the susceptibility to cKS in individuals with HHV-8 infection.
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Variación Genética , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Proteínas de la Membrana/genética , Sarcoma de Kaposi/genética , Proteínas del Envoltorio Viral/genética , Adulto , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Femenino , Humanos , Masculino , Persona de Mediana Edad , FilogeniaRESUMEN
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent of all forms of Kaposi's sarcoma (KS), including AIDS-KS, endemic KS, classic KS and iatrogenic KS. Based on Open reading frame (ORF) K1 sequence analysis, KSHV has been classified into seven major molecular subtypes (A, B, C, D, E, F and Z). The distribution of KSHV strains varies according to geography and ethnicity. Xinjiang is a unique region where the seroprevalence of KSHV is significantly higher than other parts of China. The genotyping of KSHV strains in this region has not been thoroughly studied. The present study aimed to evaluate the frequency of KSHV genotypes isolated from KS tissues in Classical KS and AIDS KS patients from Xinjiang, China. ORF-K1 of KSHV from tissue samples of 28 KS patients was amplified and sequenced. Two subtypes of KSHV were identified according to K1 genotyping. Twenty-three of them belonged to subtype A, while five of them were subtype C. More genotype A than genotype C strains were found in both Classical KS and AIDS KS. No significant difference was found in the prevalence of different genotype between Classical KS and AIDS KS.