RESUMEN
JAK-STAT signaling pathway has a crucial role in host innate immunity against viral infections, including HIV-1. We therefore examined the impact of HIV-1 infection and combination antiretroviral therapy (cART) on JAK-STAT signaling pathway. Compared to age-matched healthy donors (n = 18), HIV-1-infected subjects (n = 18) prior to cART had significantly lower expression of toll-like receptors (TLR-1/4/6/7/8/9), the IFN regulatory factors (IRF-3/7/9), and the antiviral factors (OAS-1, MxA, A3G, PKR, and Tetherin). Three months' cART partially restores the impaired functions of JAK-STAT-mediated antiviral immunity. We also found most factors had significantly positive correlations (p < 0.05) between each two factors in JAK-STAT pathway in healthy donors (98.25%, 168/171), but such significant positive associations were only found in small part of HIV-1-infected subjects (43.86%, 75/171), and stably increased during the cART (57.31%, 98/171 after 6 months' cART). With regard to the restoration of some HIV-1 restriction factors, HIV-1-infected subjects who had CD4+ T cell counts > 350//µl responded better to cART than those with the counts < 350/µl. These findings indicate that the impairment of JAK-STAT pathway may play a role in the immunopathogenesis of HIV-1 disease.
Asunto(s)
Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos/efectos de los fármacos , Quimioterapia Combinada , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Adulto , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Femenino , Infecciones por VIH/inmunología , Humanos , Quinasas Janus/metabolismo , Masculino , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Carga Viral , Adulto JovenRESUMEN
MicroRNAs (miRNAs) participate in host innate immunity against HIV-1 infection. We examined the impact of HIV-1 infection on viral restriction miRNAs in plasma of HIV-1-infected subjects. HIV-1-infected subjects had significantly lower plasma levels of HIV-1 restriction miRNAs (miRs-29a, -29b, -125b, -223, -198, and -382) than control subjects. Further in vitro studies showed that HIV-1 infection of macrophages suppressed production of the extracellular miRs-29b, -125b, and -223. These data demonstrate the compelling evidence that HIV-1 infection impairs host innate immunity by inhibiting antiviral miRNAs, which provide a possible mechanism for HIV-1 persistence in the host.
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Antivirales/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/patología , VIH-1/inmunología , Tolerancia Inmunológica , MicroARNs/sangre , Adulto , Femenino , Humanos , Evasión Inmune , Masculino , Persona de Mediana EdadRESUMEN
Human metapneumovirus (HMPV) is a worldwide distributed pathogen of the respiratory tract. The objectives of this study were to identify HMPV infections among children with influenza-like illness (ILI) in Wuhan and to assess circulation patterns and molecular diversity of HMPV in this area. From July 2008 to December 2013, a total of 3,883 throat swab samples were collected from ILI outpatients under 16 years old. HMPV RNA was detected in 171 samples (4.40%). All the four subtypes of HMPV were identified, among which A2 was the most common subtype (61/145, 42.1%), followed by B1, B2, and A1. During the study period, HMPV circulation presented a biennial alternation between high and low incidence in Wuhan and the seasonal peak also shift between winter and spring in two continuous seasons. Subtype A2, B1, and B2 co-circulated during the study period, with genotype A prevailing in epidemic season 2008-2009 and 2012-2013, and genotype B prevailing during other periods. This large-scale analysis of HMPV prevalence in ILI outpatient children improves the understanding of local HMPV circulation patterns and provides molecular epidemic evidence for comparative analysis of HMPV infection.
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Variación Genética , Genotipo , Gripe Humana/patología , Metapneumovirus/clasificación , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/patología , Adolescente , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Metapneumovirus/genética , Epidemiología Molecular , Pacientes Ambulatorios , Infecciones por Paramyxoviridae/virología , Faringe/virología , ARN Viral/análisis , Estaciones del AñoRESUMEN
Although opioids have been extensively studied for their impact on the immune system, limited information is available about the specific actions of opioids on intracellular antiviral innate immunity against HIV infection. Thus, we investigated whether heroin, one of the most abused drugs, inhibits the expression of intracellular HIV restriction microRNA (miRNA) and facilitates HIV replication in macrophages. Heroin treatment of macrophages enhanced HIV replication, which was associated with the downregulation of several HIV restriction miRNAs. These heroin-mediated actions on the miRNAs and HIV could be antagonized by naltrexone, an opioid receptor antagonist. Furthermore, the in vitro negative impact of heroin on HIV-associated miRNAs was confirmed by the in vivo observation that heroin addicts had significantly lower levels of macrophage-derived HIV restriction miRNAs than those in the control subjects. These in vitro and in vivo findings indicate that heroin use compromises intracellular anti-HIV innate immunity, providing a favorable microenvironment for HIV survival in the target cells.
RESUMEN
BACKGROUND: Hand, foot, and mouth disease (HFMD) is an infectious disease caused by a group of enteroviruses, including Coxsackievirus A16 (CVA16) and Enterovirus A71 (EV-A71). In recent decades, Asian countries have experienced frequent and widespread HFMD outbreaks, with deaths predominantly among children. In several Asian countries, epidemics usually peak in the late spring/early summer, with a second small peak in late autumn/early winter. We investigated the possible underlying association between the seasonality of HFMD epidemics and meteorological variables, which could improve our ability to predict HFMD epidemics. METHODS: We used a time series analysis composed of a spectral analysis based on the maximum entropy method (MEM) in the frequency domain and the nonlinear least squares method in the time domain. The time series analysis was applied to three kinds of monthly time series data collected in Wuhan, China, where high-quality surveillance data for HFMD have been collected: (i) reported cases of HFMD, (ii) reported cases of EV-A71 and CVA16 detected in HFMD patients, and (iii) meteorological variables. RESULTS: In the power spectral densities for HFMD and EV-A71, the dominant spectral lines were observed at frequency positions corresponding to 1-year and 6-month cycles. The optimum least squares fitting (LSF) curves calculated for the 1-year and 6-month cycles reproduced the bimodal cycles that were clearly observed in the HFMD and EV-A71 data. The peak months on the LSF curves for the HFMD data were consistent with those for the EV-A71 data. The risk of infection was relatively high at 10 °C ≤ t < 15 °C (t, temperature [°C]) and 15 °C ≤ t < 20 °C, and peaked at 20 °C ≤ t < 25 °C. CONCLUSION: In this study, the HFMD infections occurring in Wuhan showed two seasonal peaks, in summer (June) and winter (November or December). The results obtained with a time series analysis suggest that the bimodal seasonal peaks in HFMD epidemics are attributable to EV-A71 epidemics. Our results suggest that controlling the spread of EV-A71 infections when the temperature is approximately 20-25 °C should be considered to prevent HFMD infections in Wuhan, China.
Asunto(s)
Enfermedad de Boca, Mano y Pie/epidemiología , Niño , Preescolar , China/epidemiología , Enfermedades Transmisibles/epidemiología , Brotes de Enfermedades , Enterovirus/patogenicidad , Infecciones por Enterovirus/epidemiología , Humanos , Lactante , Recién Nacido , Análisis de los Mínimos Cuadrados , Modelos Teóricos , Estaciones del Año , Temperatura , Tiempo (Meteorología)RESUMEN
BACKGROUND: Mobile populations and men who have sex with men (MSM) play an increasing role in the current HIV epidemic in China and across the globe. While considerable research has addressed both of these at-risk populations, more effective HIV control requires accurate data on the number of MSM at the population level, particularly MSM among migrant populations. METHODS: Survey data from a random sample of male rural-to-urban migrants (aged 18-45, n=572) in Wuhan, China were analyzed and compared with those of randomly selected non-migrant urban (n=566) and rural counterparts (580). The GIS/GPS technologies were used for sampling and the survey estimation method was used for data analysis. RESULTS: HIV-related risk behaviors among rural-to-urban migrants were similar to those among the two comparison groups. The estimated proportion of MSM among migrants [95% CI] was 5.8% [4.7, 6.8], higher than 2.8% [1.2, 4.5] for rural residents and 1.0% [0.0, 2.4] for urban residents, respectively. Among these migrants, the MSM were more likely than non-MSM to be older in age, married, and migrated to more cities. They were also more likely to co-habit with others in rental properties located in new town and neighborhoods with fewer old acquaintances and more entertainment establishments. In addition, they were more likely to engage in commercial sex and less likely to consistently use condoms. CONCLUSION: Findings of this study indicate that compared to rural and urban populations, the migrant population in Wuhan consists of a higher proportion of MSM who also exhibit higher levels of HIV-related risk behaviors. More effective interventions should target this population with a focus on neighborhood factors, social capital and collective efficacy for risk reduction.
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Bisexualidad/estadística & datos numéricos , Homosexualidad Masculina/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Conducta Sexual/estadística & datos numéricos , Migrantes/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , China/epidemiología , Condones/estadística & datos numéricos , Sistemas de Información Geográfica , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Humanos , Actividades Recreativas , Masculino , Persona de Mediana Edad , Características de la Residencia/estadística & datos numéricos , Conducta de Reducción del Riesgo , Asunción de Riesgos , Muestreo , Trabajo Sexual/estadística & datos numéricos , Factores Socioeconómicos , Sexo Inseguro/estadística & datos numéricos , Adulto JovenRESUMEN
We report here the whole genomic analyses of two G4P[6] (RVA/Human-wt/CHN/E931/2008/G4P[6], RVA/Human-wt/CHN/R1954/2013/G4P[6]), one G3P[6] (RVA/Human-wt/CHN/R946/2006/G3P[6]) and one G4P[8] (RVA/Human-wt/CHN/E2484/2011/G4P[8]) group A rotavirus (RVA) strains detected in sporadic cases of diarrhea in humans in the city of Wuhan, China. All the four strains displayed a Wa-like genotype constellation. Strains E931 and R1954 shared a G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1 constellation, whilst the 11 gene segments of strains R946 and E2484 were assigned to G3-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 and G4-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 genotypes, respectively. Phylogenetically, the VP7 gene of R946, NSP3 gene of E931, and 10 of 11 gene segments of E2484 (except for VP7 gene) belonged to lineages of human RVAs. On the other hand, based on available data, it was difficult to ascertain porcine or human origin of VP3 genes of strains E931 and R946, and NSP2 genes of strains R946 and R1954. The remaining genes of E2484, E931, R946 and R1954 were close to those of porcine RVAs from China, and/or porcine-like human RVAs. Taken together, our observations suggested that strain R1954 might have been derived from porcine RVAs, whilst strains R946 and E931 might be reassortants possessing human RVA-like gene segments on a porcine RVA genetic backbone. Strain E2484 might be derived from reassortment events involving acquisition of a porcine-like VP7 gene by a Wa-like human RVA strain. The present study provided important insights into zoonotic transmission and complex reassortment events involving human and porcine RVAs, reiterating the significance of whole-genomic analysis of RVA strains.
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Genómica , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/microbiología , Rotavirus/genética , Proteínas Virales/genética , Alelos , Sustitución de Aminoácidos , Animales , Genoma Viral , Genotipo , Humanos , Mutación , Filogenia , Virus Reordenados , Rotavirus/clasificación , Infecciones por Rotavirus/transmisiónRESUMEN
Hepatitis C virus (HCV) infection is common among injection drug users (IDUs). There is accumulating evidence that circulating microRNAs (miRNAs) are associated with HCV infection and disease progression. The present study was undertaken to determine the in vivo impact of heroin use on HCV infection and HCV-related circulating miRNA expression. Using the blood specimens from four groups of the study subjects (HCV-infected individuals, heroin users with/without HCV infection, and healthy volunteers), we found that HCV-infected heroin users had significantly higher viral load than HCV-infected non-heroin users (p = 0.0004). Measurement of HCV-related circulating miRNAs in plasma showed that miRs-122, 141, 29a, 29b, and 29c were significantly increased in the heroin users with HCV infection, whereas miR-351, an HCV inhibitory miRNA, was significantly decreased in heroin users as compared to control subjects. Further investigation identified a negative correlation between the plasma levels of miR-29 family members and severity of HCV infection based on aspartate aminotransferase to platelet ratio index (APRI). In addition, heroin use and/or HCV infection also dysregulated a panel of plasma miRNAs. Taken together, these data for the first time revealed in vivo evidence that heroin use and/or HCV infection alter circulating miRNAs, which provides a novel mechanism for the impaired innate anti-HCV immunity among IDUs.
Asunto(s)
Hepatitis C/etiología , Dependencia de Heroína/complicaciones , MicroARNs/metabolismo , Adulto , Aspartato Aminotransferasas/sangre , Femenino , Regulación Viral de la Expresión Génica/efectos de los fármacos , Hepacivirus , Dependencia de Heroína/metabolismo , Dependencia de Heroína/virología , Humanos , Masculino , MicroARNs/efectos de los fármacos , Persona de Mediana Edad , Recuento de Plaquetas , ARN Viral/sangre , Carga ViralRESUMEN
Although segmented and unsegmented RNA viruses are commonplace, the evolutionary links between these two very different forms of genome organization are unclear. We report the discovery and characterization of a tick-borne virus--Jingmen tick virus (JMTV)--that reveals an unexpected connection between segmented and unsegmented RNA viruses. The JMTV genome comprises four segments, two of which are related to the nonstructural protein genes of the genus Flavivirus (family Flaviviridae), whereas the remaining segments are unique to this virus, have no known homologs, and contain a number of features indicative of structural protein genes. Remarkably, homology searching revealed that sequences related to JMTV were present in the cDNA library from Toxocara canis (dog roundworm; Nematoda), and that shared strong sequence and structural resemblances. Epidemiological studies showed that JMTV is distributed in tick populations across China, especially Rhipicephalus and Haemaphysalis spp., and experiences frequent host-switching and genomic reassortment. To our knowledge, JMTV is the first example of a segmented RNA virus with a genome derived in part from unsegmented viral ancestors.
Asunto(s)
Flaviviridae/genética , Genoma Viral , Garrapatas/virología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos , Línea Celular , China , ADN Viral/genética , Perros , Evolución Molecular , Flaviviridae/clasificación , Flaviviridae/ultraestructura , Flavivirus/genética , Microscopía Electrónica de Transmisión , Datos de Secuencia Molecular , Filogenia , Proteómica , Virus Reordenados/clasificación , Virus Reordenados/genética , Virus Reordenados/ultraestructura , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Proteínas no Estructurales Virales/genéticaRESUMEN
BACKGROUND: Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. Since the latter of the 1990s, G3 human rotaviruses referred to as "new variant G3" have emerged and spread in China, being a dominant genotype until 2010, although their genomic evolution has not yet been well investigated. METHODS: The complete genomes of 33 G3P[8] human rotavirus strains detected in Wuhan, China, from 2000 through 2013 were analyzed. Phylogenetic trees of concatenated sequences of all the RNA segments and individual genes were constructed together with published rotavirus sequences. RESULTS: Genotypes of 11 gene segments of all the 33 strains were assigned to G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, belonging to Wa genogroup. Phylogenetic analysis of the concatenated full genome sequences indicated that all the modern G3P[8] strains were assigned to Cluster 2 containing only one clade of G3P[8] strains in the US detected in the 1970s, which was distinct from Cluster 1 comprising most of old G3P[8] strains. While main lineages of all the 11 gene segments persisted during the study period, different lineages appeared occasionally in RNA segments encoding VP1, VP4, VP6, and NSP1-NSP5, exhibiting various allele constellations. In contrast, only a single lineage was detected for VP7, VP2, and VP3 genes. Remarkable lineage shift was observed for NSP1 gene; lineage A1-2 emerged in 2007 and became dominant in 2008-2009 epidemic season, while lineage A1-1 persisted throughout the study period. CONCLUSION: Chinese G3P[8] rotavirus strains have evolved since 2000 by intra-genogroup reassortment with co-circulating strains, accumulating more reassorted genes over the years. This is the first large-scale whole genome-based study to assess the long-term evolution of common human rotaviruses (G3P[8]) in an Asian country.
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Evolución Molecular , Genoma Viral , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Rotavirus/genética , Sustitución de Aminoácidos , China/epidemiología , Frecuencia de los Genes , Genes Virales , Variación Genética , Genotipo , Historia del Siglo XXI , Humanos , Fenotipo , Filogenia , Prevalencia , ARN Viral , Rotavirus/clasificación , Infecciones por Rotavirus/historia , Estaciones del Año , Análisis de Secuencia de ADN , Análisis Espacio-TemporalRESUMEN
The group A rotavirus (RVA) G3P[9] is a rare VP7-VP4 genotype combination, detected occasionally in humans and cats. Other than the prototype G3P[9] strain, RVA/Human- tc/JPN/AU-l/1982/G3P3[9], the whole genomes of only two human G3P[9] RVA strains and two feline G3P[9] RVA strains have been analyzed so far, revealing complex evolutionary patterns, distinct from that of AU-1. We report here the whole genomic analyses of two human G3P[9] RVA strains, RVA/Human-tc/CHN/L621/2006/G3P[9] and RVA/Human-wt/CHN/E2451/2011/G3P[9], detected in patients with diarrhea in China. Strains L621 and E2451 possessed a H6 NSP5 genotype on an AU-1-like genotype constellation, not reported previously. However, not all the genes of L621 and E2451 were closely related to those of AU-1, or to each other, revealing different evolutionary patterns among the AU-1-like RVAs. The VP7, VP4, VP6 and NSP4 genes of E2451 and L621 were found to cluster together with human G3P[9] RVA strains believed to be of possible feline/canine origin, and feline or raccoon dog RVA strains. The VP1, VP3, NSP2 and NSP5 genes of E2451 and L621 formed distinct clusters in genotypes typically found in feline/canine RVA strains or RVA strains from other host species which are believed to be of feline/canine RVA origin. The VP2 genes of E2451 and L621, and NSP3 gene of L621 clustered among RVA strains from different host species which are believed to have a complete or partial feline/canine RVA origin. The NSP1 genes of E2451 and L621, and NSP3 gene of E2451 clustered with AU-1 and several other strains possessing a complete or partial feline RVA strain BA222-05-like genotype constellation. Taken together, these observations suggest that nearly all the eleven gene segments of G3P[9] RVA strains L621 and E2451 might have originated from feline/canine RVAs, and that reassortments may have occurred among these feline/canine RVA strains, before being transmitted to humans.
Asunto(s)
Infecciones por Rotavirus/virología , Rotavirus/genética , Animales , Gatos , Preescolar , Perros , Genoma Viral , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Rotavirus/clasificación , Infecciones por Rotavirus/genética , Proteínas no Estructurales Virales/genéticaRESUMEN
G1P[8] rotaviruses are an important cause of diarrhea in humans in China. To date, there are no reports on the whole genomic analysis of the Chinese G1P[8] rotaviruses. To determine the origin and overall genetic makeup of the recent Chinese G1P[8] strains, the whole genomes of three strains, RVA/Human-wt/CHN/E1911/2009/G1P[8], RVA/Human-tc/CHN/R588/2005/G1P[8] and RVA/Human-tc/CHN/Y128/2004/G1P[8], detected in an infant, a child and an adult, respectively, were analyzed. Strains E1911, R588 and Y128 exhibited a typical Wa-like genotype constellation. Except for the NSP3 gene of E1911, the whole genomes of strains E1911, R588 and Y128 were found to be more closely related to those of the recent Wa-like common human strains from different countries than those of the prototype G1P[8] strain, or other old strains. On the other hand, the NSP3 gene of E1911 was genetically distinct from those of Y128, R588, or other Wa-like common human strains, and appeared to share a common origin with those of the porcine-like human G9 strains, providing evidence for intergenotype reassortment events. Comparisons of the amino acid residues defining the VP7 and VP4 antigenic domains revealed several mismatches between these Chinese G1P[8] strains and the G1 and P[8] strains contained in the currently licensed rotavirus vaccines Rotarix(TM )and RotaTeq(TM).
Asunto(s)
Diarrea/virología , Genoma Viral , Infecciones por Rotavirus/virología , Rotavirus/genética , Rotavirus/aislamiento & purificación , Anciano , Secuencia de Aminoácidos , Preescolar , China , Genómica , Genotipo , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Filogenia , Rotavirus/química , Rotavirus/clasificación , Alineación de Secuencia , Análisis de Secuencia de ADN , Proteínas Virales/química , Proteínas Virales/genéticaRESUMEN
Hemorrhagic fever with renal syndrome (HFRS) has been a significant public problem since the first cases were reported in 1961 in Wuhan city (capital of Hubei province of China). Epidemiological surveys were carried out to better understand the dynamics of hantavirus infection in humans and animals in Wuhan. During 1961-2011, a total of 21,820 HFRS cases were registered in Wuhan. The two large epidemics had occurred during 1970-1991. They reached peaks in 1973 and 1983, respectively. There have been <10 cases since 2005. The disease occurred in the whole region including the downtown areas, but mainly in two districts. Although in 1980s and 1990s HFRS cases mainly recorded in August and winter, since 2000 the disease has mainly occurred in spring and summer. In this study, hantaviruses were identified in Apodemus mice, Rattus rats, and Mus mice by indirect immunofluorescent-assay and RT-PCR. Serological and genetic analyses showed that Hantaan virus (HTNV) and Seoul virus (SEOV) co-circulated in rodents. Phylogenetic analysis of hantaviral genome sequences revealed a novel genetic lineage of HTNV circulating in rodents in Wuhan. Another lineage of HTNV was closely related to the lineages from the provinces located in the origin and delta of Yangtze River. Remarkably, SEOV variants identified in Wuhan were more closely related to the variants found outside China. Results of the present study showed that HFRS cases in Wuhan are caused by HTNV and SEOV. Phylogenetic analysis of the hantavirus sequences revealed that a novel genetic lineage of HTNV is present in rodents in Wuhan.
Asunto(s)
Virus Hantaan/clasificación , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Fiebre Hemorrágica con Síndrome Renal/virología , Virus Seoul/clasificación , Animales , Anticuerpos Antivirales/sangre , China/epidemiología , Epidemias , Genes Virales/genética , Virus Hantaan/genética , Virus Hantaan/aislamiento & purificación , Humanos , Ratones , Filogenia , Prevalencia , ARN Viral/análisis , ARN Viral/química , Ratas , Estaciones del Año , Virus Seoul/genética , Virus Seoul/aislamiento & purificaciónRESUMEN
OBJECTIVE: To identify and analyze the genetic characteristics of nucleoprotein (N) and glycoprotein (G) genes of rabies virus (RABV) isolated from a donkey in Wuhan. N gene and G gene of the virus were compared with other representative street strains isolated around Hubei areas as well as the vaccine strains used in China and abroad. METHODS: RABV in brain tissue of a donkey was detected by direct immunofluorescent method and then inoculated in suckling mice to observe the incidence of rabies. Brain samples of the donkey and infected suckling mice were detected by ELISA. The N gene and G gene fragment of the isolated RABV were amplified by RT-PCR and cloned into pMD18-T vector for sequencing and genetic analysis. RESULTS: RABVs were detected in both donkey brain and suckling mice brain samples. The N gene and G gene nucleotide homology of RABV isolated from the donkey with other representative street strains found around Hubei areas as well as vaccine strains used in China and abroad were 85.7% - 99.1% and 82.2% - 99.7%, and the deduced amino acid identity were 95.6% - 99.8% and 87.8% - 99.4%, respectively. CONCLUSION: Novel RABV was successfully identified and isolated from a donkey and showed close relationship to the representative street strains found around Hubei areas as well as vaccine strains used in China through genetic analysis.
Asunto(s)
Equidae/virología , Virus de la Rabia/genética , Animales , Antígenos Virales/genética , Encéfalo/virología , China , Glicoproteínas/genética , Ratones , Proteínas de la Nucleocápside/genética , Virus de la Rabia/aislamiento & purificación , Proteínas del Envoltorio Viral/genéticaRESUMEN
To study epidemiological features and genetic characteristics of noroviruses in children and adults with acute gastroenteritis, fecal specimens were collected in three hospitals from Jan. 2007 to May 2010 in Wuhan, China. Noroviruses were detected in 25.9 % (286/1103) and 24.6 % (202/822) of the specimens from children and adults, respectively, with genogroup II (GII) being predominant (99.2 %). The most frequent genotype among GII strains was GII.4 (2006b variant) (77.3 %) (72.0 % in children and 87.9 % in adults), followed by GII.3 (15.0 %) and GII.6 (3.4 %). Potential recombinant genotypes (polymerase/capsid) were detected in 51 GII strains (15.9 %), including the most frequent type, GII.12/GII.3 (28 strains), and GII.16/GII.2, detected for the first time in China, which were found in only children. The results indicated that genetically similar noroviruses were circulating among children and adults as a cause of gastroenteritis, except for some recombinant genotypes.
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Infecciones por Caliciviridae/virología , Gastroenteritis/virología , Norovirus/clasificación , Norovirus/genética , Adolescente , Adulto , Anciano , Infecciones por Caliciviridae/epidemiología , Niño , Preescolar , China/epidemiología , Heces/virología , Femenino , Gastroenteritis/epidemiología , Variación Genética , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Prevalencia , Virus Reordenados , Adulto JovenRESUMEN
The complete genomic sequence of a rabies virus isolate WH11, isolated from brain tissue of a rabid donkey in China, was determined and compared with other rabies viruses. This is the first Chinese street strain which was isolated from donkey and the entire length and organization of the virus was similar to that of other rabies viruses. Multiple alignments of amino acid sequences of the nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and large protein of WH11 with those of other rabies viruses were undertaken to examine the conservative degree of functional regions. Phylogenetic analysis using the complete genomic sequence of WH11 determined that this isolate is most closely related with rabies viruses previously isolated in China and the attenuated Chinese vaccine strain CTN181.
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Equidae/virología , Genoma Viral , Virus de la Rabia/genética , Rabia/veterinaria , Secuencia de Aminoácidos , Animales , Antígenos Virales/genética , Encéfalo/virología , China , Secuencia Conservada , Glicoproteínas/genética , Chaperonas Moleculares , Datos de Secuencia Molecular , Proteínas de la Nucleocápside/genética , Fosfoproteínas/genética , Filogenia , ARN Viral/genética , Rabia/virología , Virus de la Rabia/aislamiento & purificación , Alineación de Secuencia , Proteínas del Envoltorio Viral/genética , Proteínas Estructurales Virales/genéticaRESUMEN
BACKGROUND: Interferon lambda 3 (IFN-λ3) is a newly identified cytokine with antiviral activity, and its single nucleotide polymorphisms are strongly associated with the treatment effectiveness and development of chronic hepatitis C virus infection. We thus examined the potential of IFN-λ3 to inhibit HIV replication and the possible mechanisms of the anti-HIV action by IFN-λ3 in human macrophages. PRINCIPAL FINDINGS: Under different conditions (before, during, and after HIV infection), IFN-λ3 significantly inhibited viral replication in macrophages, which was associated with the induction of multiple antiviral cellular factors (ISG56, MxA, OAS-1, A3G/F and tetherin) and IFN regulatory factors (IRF-1, 3, 5, 7 and 9). This anti-HIV action of IFN-λ3 could be compromised by the JAK-STAT inhibitor. In addition, IFN-λ3 treatment of macrophages induced the expression of toll-like receptor 3 (TLR3) and two key adaptors (MyD88 and TRIF) in type I IFN pathway activation. However, HIV infection compromised IFN-λ3-mediated induction of the key elements in JAK-STAT signaling pathway. CONCLUSIONS: These data indicate that IFN-λ3 exerts its anti-HIV function by activating JAK-STAT pathway-mediated innate immunity in macrophages. Future in vivo studies are necessary in order to explore the potential for developing IFN-λ3-based therapy for HIV disease.
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VIH-1/efectos de los fármacos , Interleucinas/farmacología , Quinasas Janus/inmunología , Macrófagos/efectos de los fármacos , Factores de Transcripción STAT/inmunología , Transducción de Señal/efectos de los fármacos , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/inmunología , Antígenos de Diferenciación de Linfocitos B/genética , Antígenos de Diferenciación de Linfocitos B/inmunología , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , VIH-1/fisiología , Humanos , Inmunidad Innata , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/inmunología , Interferones , Interleucinas/inmunología , Quinasas Janus/antagonistas & inhibidores , Quinasas Janus/genética , Macrófagos/inmunología , Macrófagos/virología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/inmunología , Factores de Transcripción STAT/genética , Receptor Toll-Like 3/genética , Receptor Toll-Like 3/inmunología , Replicación Viral/efectos de los fármacosRESUMEN
Influenza-like illness can be caused by a wide range of respiratory viruses. In order to investigate the epidemiology of viral pathogens related to influenza-like illness in children of Wuhan, the largest city in central China, throat swab samples were collected from 1,472 young patients, from July 2008 to June 2010, before and after the occurrence of the 2009 pandemic influenza A (H1N1) virus (pH1N1). It was found that 923 patients (62.7%) were positive for at least 1 virus and 90 patients (9.8%) were detected for multiple (≥2) respiratory viruses by real-time PCR detection of 16 viruses. Seasonal influenza A virus was the predominant pathogen among all the 16 viruses with a positive rate of 13.3% (196/1,472), which was followed by pH1N1 (159/1,472). It was also noted that the viral distribution pattern in Wuhan changed upon the introduction of the pH1N1 virus.
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Gripe Humana/epidemiología , Gripe Humana/virología , Orthomyxoviridae/clasificación , Orthomyxoviridae/aislamiento & purificación , Adolescente , Pueblo Asiatico , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Orthomyxoviridae/genética , Faringe/virología , Reacción en Cadena de la Polimerasa , PrevalenciaRESUMEN
Surveys were carried out to better understand the tick vector ecology and genetic diversity of Huaiyangshan virus (HYSV) in both regions of endemicity and regions of nonendemicity. Haemaphysalis longicornis ticks were dominant in regions of endemicity, while Rhipicephalus microplus is more abundant in regions of nonendemicity. HYSV RNA was found in human and both tick species, with greater prevalence in H. longicornis and lesser prevalence in R. microplus. Phylogenetic analyses indicate that HYSV is a novel species of the genus Phlebovirus.
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Vectores Arácnidos/virología , Infecciones por Bunyaviridae/virología , Bunyaviridae/clasificación , Bunyaviridae/genética , Variación Genética , Filogenia , Rhipicephalus/virología , Animales , Bunyaviridae/aislamiento & purificación , China , Ecosistema , Humanos , Datos de Secuencia MolecularRESUMEN
BACKGROUND: Hemorrhagic fever-like illness caused by a novel Bunyavirus, Huaiyangshan virus (HYSV, also known as Severe Fever with Thrombocytopenia virus [SFTSV] and Fever, Thrombocytopenia and Leukopenia Syndrome [FTLS]), has recently been described in China. METHODS: Patients with laboratory-confirmed HYSV infection who were admitted to Union Hospital or Zhongnan Hospital between April 2010 and October 2010 were included in this study. Clinical and routine laboratory data were collected and blood, throat swab, urine, or feces were obtained when possible. Viral RNA was quantified by real-time reverse-transcriptase polymerase chain reaction. Blood levels of a range of cytokines, chemokines, and acute phase proteins were assayed. RESULTS: A total of 49 patients with hemorrhagic fever caused by HYSV were included; 8 (16.3%) patients died. A fatal outcome was associated with high viral RNA load in blood at admission, as well as higher serum liver transaminase levels, more pronounced coagulation disturbances (activated partial thromboplastin time, thrombin time), and higher levels of acute phase proteins (phospholipase A, fibrinogen, hepcidin), cytokines (interleukin [IL]-6, IL-10, interferon-γ), and chemokines (IL-8, monocyte chemotactic protein 1, macrophage inflammatory protein 1b). The levels of these host parameters correlated with viral RNA levels. Blood viral RNA levels gradually declined over 3-4 weeks after illness onset, accompanied by resolution of symptoms and laboratory abnormalities. Viral RNA was also detectable in throat, urine, and fecal specimens of a substantial proportion of patients, including all fatal cases assayed. CONCLUSIONS. Viral replication and host immune responses play an important role in determining the severity and clinical outcome in patients with infection by HYSV.