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1.
Proc Natl Acad Sci U S A ; 111(18): 6744-9, 2014 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24753611

RESUMO

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.


Assuntos
Flaviviridae/genética , Genoma Viral , Carrapatos/virologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Linhagem Celular , China , DNA Viral/genética , Cães , Evolução Molecular , Flaviviridae/classificação , Flaviviridae/ultraestrutura , Flavivirus/genética , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Filogenia , Proteômica , Vírus Reordenados/classificação , Vírus Reordenados/genética , Vírus Reordenados/ultraestrutura , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Proteínas não Estruturais Virais/genética
2.
J Virol ; 86(2): 972-81, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22090114

RESUMO

Despite the worldwide distribution, most of the known Seoul viruses (SEOV) are closely related to each other. In this study, the M and the S segment sequences of SEOV were recovered from 130 lung tissue samples (mostly of Norway rats) and from six patient serum samples by reverse transcription-PCR. Genetic analysis revealed that all sequences belong to SEOV and represent 136 novel strains. Phylogenetic analysis of all available M and S segment sequences of SEOV, including 136 novel Chinese strains, revealed four distinct groups. All non-Chinese SEOV strains and most of the Chinese variants fell into the phylogroup A, while the Chinese strains originating from mountainous areas clustered into three other distinct groups (B, C, and D). We estimated that phylogroup A viruses may have arisen only within the last several centuries. All non-Chinese variants appeared to be directly originated from China. Thus, phylogroup A viruses distributed worldwide may share a recent ancestor, whereas SEOV seems to be as diversified genetically as other hantaviruses. In addition, all available mitochondrial DNA (mtDNA) sequences of Norway rats, including our 44 newly recovered mtDNA sequences, were divided into two phylogenetic groups. The first group, which is associated with the group A SEOV variants, included most of rats from China and also all non-Chinese rats, while the second group consisted of a few rats originating only from mountain areas in China. We hypothesize that an ancestor of phylogroup A SEOV variants was first exported from China to Europe and then spread through the New World following the migration of Norway rats.


Assuntos
Migração Animal , Reservatórios de Doenças/virologia , Febre Hemorrágica com Síndrome Renal/virologia , Ratos/virologia , Vírus Seoul/isolamento & purificação , Animais , Reservatórios de Doenças/classificação , Humanos , Dados de Sequência Molecular , Filogenia , Filogeografia , Ratos/classificação , Ratos/fisiologia , Vírus Seoul/classificação , Vírus Seoul/genética , Proteínas Virais/genética
3.
J Virol ; 86(5): 2864-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22190717

RESUMO

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.


Assuntos
Vetores Aracnídeos/virologia , Infecções por Bunyaviridae/virologia , Bunyaviridae/classificação , Bunyaviridae/genética , Variação Genética , Filogenia , Rhipicephalus/virologia , Animais , Bunyaviridae/isolamento & purificação , China , Ecossistema , Humanos , Dados de Sequência Molecular
4.
Clin Infect Dis ; 54(4): 527-33, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22144540

RESUMO

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.


Assuntos
Infecções por Bunyaviridae/diagnóstico , Infecções por Bunyaviridae/mortalidade , Febres Hemorrágicas Virais/diagnóstico , Febres Hemorrágicas Virais/mortalidade , Orthobunyavirus/classificação , Orthobunyavirus/isolamento & purificação , Adulto , Idoso , Sangue/virologia , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/patologia , China/epidemiologia , Fezes/virologia , Feminino , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Faringe/virologia , Estudos Prospectivos , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Análise de Sobrevida , Urina/virologia , Carga Viral
5.
Am J Pathol ; 178(1): 41-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21224041

RESUMO

Several micro RNAs (miRNAs) have the ability to inhibit HIV replication in target cells. Thus, we investigated the impact of opioids (morphine and heroin), widely abused drugs among people infected with HIV, on the expression of cellular anti-HIV miRNAs in monocytes. We found that morphine-treated monocytes expressed lower levels of cellular anti-HIV miRNAs than untreated cells. In addition, morphine treatment of monocytes compromised type I interferon (IFN)-induced anti-HIV miRNA expression. These findings paralleled the observation that morphine treatment of monocytes enhanced HIV replication. These morphine-mediated actions on the anti-HIV miRNAs and HIV could be antagonized by the opioid receptor antagonists (naltrexone or Cys2, Tyr3, Arg5, Pen7-amide). Furthermore, the in vitro impact of morphine on miRNA expression was confirmed by the in vivo observation that heroin-dependent subjects had significantly lower levels of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in peripheral blood mononuclear cells than the healthy subjects. These in vitro and in vivo findings indicate that opioid use impairs intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection.


Assuntos
Infecções por HIV/induzido quimicamente , HIV/efeitos dos fármacos , Heroína/toxicidade , MicroRNAs/antagonistas & inibidores , Monócitos/efeitos dos fármacos , Morfina/toxicidade , Replicação Viral/efeitos dos fármacos , Adulto , Células Cultivadas , HIV/fisiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Interferon-alfa/farmacologia , Interferon beta/farmacologia , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/virologia , Adulto Jovem
6.
Arch Virol ; 157(12): 2417-24, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22886184

RESUMO

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.


Assuntos
Infecções por Caliciviridae/virologia , Gastroenterite/virologia , Norovirus/classificação , Norovirus/genética , Adolescente , Adulto , Idoso , Infecções por Caliciviridae/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Variação Genética , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Prevalência , Vírus Reordenados , Adulto Jovem
7.
Arch Virol ; 156(12): 2221-31, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21986895

RESUMO

Hospital-based surveillance of rotavirus genotypes was conducted in Wuhan, China, between March 2008 and May 2011. The detection rates of group A rotavirus were 24.6% (458/1859) and 12.1% (96/795) in children and adults, respectively, with diarrhea. Among the 554 positive specimens, the most frequent genotype was G3P[8] (57.9%), followed by G1P[8] (29.4%). Compared with previous studies in Wuhan (2000-2008), the relative frequency of G3P[8] has been decreasing year by year, while the predominant genotype G3 shifted to G1 in 2011. In the present study, a rare P[8]b subtype of the VP4 gene (OP354-like P[8]) was identified in nine strains. Full-length sequences of VP7, VP4, VP6 and NSP4 genes of two G9P[8]b strains (RVA/Human-wt/CHN/E1545/2009/G9P[8]b and RVA/Human-wt/CHN/Z1108/2008/G9P[8]b) were determined for phylogenetic analysis. The four genes of these strains were closely related to one another, and the G9-VP7 genes of these strains belonged to lineage III, which contains globally spreading G9 rotaviruses. The full-length sequence of VP4 gene segments of the P[8]b strains in Wuhan clustered with those of P[8]b strains in Vietnam, Russia and Belgium, while they were distinct from those of the OP354 strain from Malawi and Bangladeshi strains. The VP6 and NSP4 genes of two P[8]b strains belonged to the I1 and E1 genotype, respectively, and clustered with those of strains belonging to Wa-like human rotaviruses from various Asian countries. These findings indicate the changing epidemiologic trend of rotavirus genotypes in Wuhan, i.e., the shift of the predominant type from G3 to G1 and the emergence of P[8]b strains genetically related to those distributed in other Asian countries.


Assuntos
Proteínas do Capsídeo/genética , Genes Virais , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/genética , Adulto , Antígenos Virais/genética , Criança , China/epidemiologia , Genótipo , Glicoproteínas/genética , Humanos , Filogenia , Rotavirus/classificação , Rotavirus/isolamento & purificação , Toxinas Biológicas/genética , Proteínas não Estruturais Virais/genética
8.
Can J Microbiol ; 57(11): 964-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22004120

RESUMO

Human astrovirus (HAstV) was an important cause of viral gastroenteritis in infants in Wuhan city based on our previous study. The aim of the study was to investigate the nature of HAstV infection in Wuhan, People's Republic of China, especially in adults. Stool specimens were collected from 361 children and 301 adults with diarrhea from July 2007 to June 2008 and were tested for HAstV RNA by RT-PCR. The 348-bp PCR product of positive samples was further sequenced and analyzed for multiple sequence alignment and phylogenetic tree. HAstV RNA was detected in 2.33% (7/301) adults, which was significantly lower than that in children (13.57%, 49/361). HAstV-positive patients were either older than 50 years of age or younger than 3. Genetic analysis showed that the HAstV strain in adults was the same as that in children in 2007-2008. Contrarily, HAstV strains prevalent in 2007-2008 showed genetic characteristics different from those in 2004-2005 and belonged to two new groups of HAstV-1b. Thus, our data characterized HAstV infection in Wuhan 2007-2008, suggesting that HAstV infection also played an important role in adults in Wuhan, especial in patients of >50 years, and should be included for routine diagnosis in the population with diarrheal illness.


Assuntos
Infecções por Astroviridae/virologia , Mamastrovirus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Astroviridae/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Fezes/virologia , Feminino , Humanos , Lactente , Masculino , Mamastrovirus/classificação , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
9.
J Med Virol ; 82(6): 1094-102, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20419827

RESUMO

During the 2004 surveillance of rotaviruses in Wuhan, China, a G4P[6] rotavirus strain R479 was isolated from a stool specimen collected from a 2-year-old child with diarrhea. The strain R479 had an uncommon subgroup specificity I + II, and analysis of the VP6 gene suggested that it was related to porcine rotaviruses. In the present study, full-length nucleotide sequences of all the RNA segments of R479 were determined and analyzed phylogenetically to identify the origin of individual RNA segments. According to the rotavirus genotyping system based on 11 RNA segments, the genotype of R479 was expressed as G4-P[6]-I5-R1-C1-M1-A1-N1-T7-E1-H1. This genotype includes the porcine-like VP6 genotype (I5) and bovine-like NSP3 genotype (T7). Phylogenetic analysis revealed that R479 genes encoding VP1, VP2, VP3, VP6, VP7, VP8*, NSP1, NSP4, and NSP5 were more closely related to those of porcine rotaviruses than human or other animal rotaviruses. In contrast, it was remarkable that the NSP3 gene of R479 was genetically closely related to only a bovine rotavirus strain UK. The NSP2 gene of R479 was also unique and clustered with only the G5P[8] human strain IAL28 and G3P[24] simian strain TUCH. These results suggested that R479 may be a reassortant virus having the NSP3 gene from a bovine rotavirus in the genetic background of a porcine rotavirus, with an NSP2 gene related to the porcine-human reassortant strain IAL28. To our knowledge, R479 is the first porcine-bovine reassortant rotavirus isolated from a human.


Assuntos
Genoma Viral , Recombinação Genética , Infecções por Rotavirus/virologia , Rotavirus/genética , Rotavirus/isolamento & purificação , Análise de Sequência de DNA , Pré-Escolar , China , Análise por Conglomerados , Fezes/virologia , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Rotavirus/classificação , Proteínas Virais/genética
10.
J Med Virol ; 81(2): 382-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19107964

RESUMO

Prevalence and phylogenetic relatedness of rotaviruses causing diarrheal diseases in children and adults were analyzed in Wuhan, China. During a period between June 2006 and February 2008, group A rotavirus was identified in 24.9% (280/1126) and 7.6% (83/1088) of specimens taken from children and adults, respectively. G3P[8] was the most frequent genotype in both children (66.3%) and adults (62.7%), followed by G1P[8] (20.3% and 26.2%, respectively). G9 was detected in specimens from six children (2.0%) and seven adults (5.6%). The VP7 genes of G3P[8] rotaviruses from children and adults showed extremely high sequence identities to each other (98.9-100%) and also to those of G3 viruses isolated in Wuhan in 2003-2004. In the phylogenetic analysis of the VP7 gene, the G3P[8] rotaviruses in Wuhan were clustered into a single lineage with some G3 viruses, which had been referred to as "the new variant G3" rotaviruses, reported recently in East Asia and Southeast Asia. Similar to G3P[8] rotaviruses, extremely high sequence identities between children and adults were observed for VP7 genes of G1 and G9 rotaviruses. The G9 viruses were clustered in the lineage of globally spreading strains, while G1 viruses were genetically close to those reported previously in China and Japan. These findings indicated the persistence of the variant G3 rotaviruses and spread of G9 rotaviruses derived from the global G9 lineage in Wuhan, and suggested that the rotaviruses were circulating among children and adults, irrelevant to the G types.


Assuntos
Fezes/virologia , Infecções por Rotavirus/genética , Rotavirus/classificação , Rotavirus/isolamento & purificação , Adolescente , Adulto , Sequência de Aminoácidos , Antígenos Virais/química , Antígenos Virais/genética , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Criança , Pré-Escolar , China , Genótipo , Humanos , Lactente , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Alinhamento de Sequência , Adulto Jovem
11.
Infect Genet Evol ; 9(1): 87-96, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19041424

RESUMO

There have been three major rabies epidemics in China since the 1950s. To gain more insights into the molecular epidemiology of rabies viruses (RVs) for the third (the current) epidemic, we isolated RV from dogs and humans in major endemic areas, and characterized these isolates genetically by sequencing the entire glycoprotein (G) gene and the G-L non-coding region. These sequences were also compared phylogenetically with RVs isolated in China during previous epidemics and those around the world. Comparison of the entire G genes among the Chinese isolates revealed up to 21.8% divergence at the nucleotide level and 17.8% at the amino acid level. The available Chinese isolates could be divided into two distinct clades, each of which could be further divided into six lineages. Viruses in clade I include most of the Chinese viruses as well as viruses from southeast Asian countries including Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. The viruses in the other clade were found infrequently in China, but are closely related to viruses distributed worldwide among terrestrial animals. Interestingly, most of the viruses isolated during the past 10 years belong to lineage A viruses within clade I whereas most of the viruses isolated before 1996 belong to other lineages within clades I and II. Our results indicated that lineages A viruses have been predominant during the past 10 years and thus are largely responsible for the third and the current epidemic in China. Our results also suggested that the Chinese RV isolates in clade I share a common recent ancestor with those circulating in southeast Asia.


Assuntos
Variação Genética , Vírus da Raiva/classificação , Vírus da Raiva/genética , Sequência de Aminoácidos , Animais , Antígenos Virais/química , Antígenos Virais/genética , Encéfalo/virologia , China , Cães , Glicoproteínas/química , Glicoproteínas/genética , Humanos , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Raiva/epidemiologia , Raiva/virologia , Vírus da Raiva/isolamento & purificação , Saliva/virologia , Alinhamento de Sequência , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas Virais/genética
12.
Virus Res ; 135(1): 191-6, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18353479

RESUMO

Since the majority of heroin abusers use injection as the primary route of admission, heroin abuse contributes significantly to the transmission of hepatitis C virus (HCV). We determined HCV infection and its genotype distribution among injection heroin users in Wuhan, the largest city in the central China. Eight hundred seventy-eight (84%) out of 1046 serum specimens from the injection drug users were positive for HCV antibody. Out of randomly selected 122 specimens positive for HCV antibody, seventy-eight (64%) had detectable HCV RNA with genotype 6a as the predominant strain (50%), followed by 3b (32.2%), 1a (8.1%), 1b (6.5%), and 3a (3.2%). HCV RNA levels in male heroin users were significantly higher (P=0.013) than those in the female subjects. Although there was no significant difference in HCV RNA levels among the specimens positive for HCV 6a and 1a/1b, the samples with 6a or 1a/1b contained higher levels of HCV RNA than the specimens positive for HCV 3b (P=0.019, P=0.012, respectively). These findings indicate that there is a high prevalence of HCV infection with genotypes 6a and 3b as predominated strains among injection heroin users in Wuhan, China.


Assuntos
Variação Genética , Hepacivirus/genética , Hepatite C/virologia , Dependência de Heroína/virologia , Adulto , Fatores Etários , Anticorpos Antivirais/sangue , China/epidemiologia , Estudos de Coortes , Feminino , Hepacivirus/classificação , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Fatores Sexuais , Proteínas Virais/genética
13.
Virus Res ; 124(1-2): 125-38, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17129631

RESUMO

A group of 31 rabies viruses (RABVs), recovered primarily from dogs, one deer and one human case, were collected from various areas in China between 1989 and 2006. Complete G gene sequences determined for these isolates indicated identities of nucleotide and amino acid sequences of >or=87% and 93.8%, respectively. Phylogenetic analysis of these and some additional Chinese isolates clearly supported the placement of all Chinese viruses in Lyssavirus genotype 1 and divided all Chinese isolates between four distinct groups (I-IV). Several variants identified within the most commonly encountered group I were distributed according to their geographical origins. A comparison of representative Chinese viruses with other isolates retrieved world-wide indicated a close evolutionary relationship between China group I and II viruses and those of Indonesia while China group III viruses formed an outlying branch to variants from Malaysia and Thailand. China group IV viruses were closely related to several vaccine strains. The predicted glycoprotein sequences of these RABVs variants are presented and discussed with respect to the utility of the anti-rabies biologicals currently employed in China.


Assuntos
Antígenos Virais/genética , Glicoproteínas/genética , Vírus da Raiva/classificação , Vírus da Raiva/genética , Raiva/virologia , Proteínas do Envelope Viral/genética , Sequência de Aminoácidos , Animais , Antígenos Virais/química , Sequência de Bases , China , Cervos , Cães , Evolução Molecular , Feminino , Genótipo , Glicoproteínas/química , Glicosilação , Humanos , Dados de Sequência Molecular , Filogenia , Raiva/veterinária , Vírus da Raiva/isolamento & purificação , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Proteínas do Envelope Viral/química
14.
Oncotarget ; 8(14): 22524-22533, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28186978

RESUMO

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.


Assuntos
Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Feminino , Infecções por HIV/imunologia , Humanos , Janus Quinases/metabolismo , Masculino , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Carga Viral , Adulto Jovem
15.
AIDS Res Hum Retroviruses ; 32(4): 386-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26607272

RESUMO

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.


Assuntos
Antivirais/sangue , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1/imunologia , Tolerância Imunológica , MicroRNAs/sangue , Adulto , Feminino , Humanos , Evasão da Resposta Imune , Masculino , Pessoa de Meia-Idade
16.
Infect Genet Evol ; 33: 55-71, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25891280

RESUMO

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.


Assuntos
Genômica , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/microbiologia , Rotavirus/genética , Proteínas Virais/genética , Alelos , Substituição de Aminoácidos , Animais , Genoma Viral , Genótipo , Humanos , Mutação , Filogenia , Vírus Reordenados , Rotavirus/classificação , Infecções por Rotavirus/transmissão
17.
Front Microbiol ; 6: 1230, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26583016

RESUMO

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.

18.
PLoS One ; 9(3): e88850, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24676363

RESUMO

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.


Assuntos
Evolução Molecular , Genoma Viral , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/genética , Substituição de Aminoácidos , China/epidemiologia , Frequência do Gene , Genes Virais , Variação Genética , Genótipo , História do Século XXI , Humanos , Fenótipo , Filogenia , Prevalência , RNA Viral , Rotavirus/classificação , Infecções por Rotavirus/história , Estações do Ano , Análise de Sequência de DNA , Análise Espaço-Temporal
19.
Infect Genet Evol ; 16: 103-12, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23403096

RESUMO

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.


Assuntos
Infecções por Rotavirus/virologia , Rotavirus/genética , Animais , Gatos , Pré-Escolar , Cães , Genoma Viral , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Rotavirus/classificação , Infecções por Rotavirus/genética , Proteínas não Estruturais Virais/genética
20.
Viruses ; 4(8): 1289-304, 2012 08.
Artigo em Inglês | MEDLINE | ID: mdl-23012626

RESUMO

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).


Assuntos
Diarreia/virologia , Genoma Viral , Infecções por Rotavirus/virologia , Rotavirus/genética , Rotavirus/isolamento & purificação , Idoso , Sequência de Aminoácidos , Pré-Escolar , China , Genômica , Genótipo , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Filogenia , Rotavirus/química , Rotavirus/classificação , Alinhamento de Sequência , Análise de Sequência de DNA , Proteínas Virais/química , Proteínas Virais/genética
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