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1.
BMC Infect Dis ; 20(1): 631, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842977

RESUMO

BACKGROUND: The drug resistance and the virologic failure of antiretroviral therapy (ART) are quite severe in Liangshan. A better understanding of the virologic failure of ART and the HIV-1 transmission network dynamics is essential for the surveillance and prevention of HIV. Here, we analyzed the HIV-1 CRF07_BC strain genetic transmission networks and their associated factors among people living with HIV-1 (PLWH) who had virologic failure of ART by using close genetic links. METHODS: The drug-resistant mutations were determined using the Stanford University HIV Drug Resistance Database. HIV-1 pol genes sequences were used for phylogenetic and genotypic drug resistance analysis. The genetic transmission networks were performed by comparing sequences, constructing the phylogenetic tree, calculating the pairwise distance, and visualizing the network. RESULTS: A total of 1050 PLWH with CRF07_BC pol sequences were finally identified and included in the genetic transmission network analysis from 2016 to 2017. Of the 1050 CRF07_BC pol sequences, 346 (32.95%) fell into clusters at a genetic distance of 0.006, resulting in 137 clusters ranging in size from 2 to 40 individuals. Subjects who were widowed or divorced were less likely to form a genetic transmission network (adjusted OR: 0.50), while subjects who had shared a needle ≥ five times were more likely to form a network (adjusted OR: 1.88). CONCLUSIONS: The genetic transmission networks revealed the complex transmission pattern, highlighting the urgent need for transmission monitoring of virologic failure of ART and selection of more effective therapeutic regimens to promote viral suppression.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/genética , Grupos Minoritários , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Genes pol , Infecções por HIV/virologia , Humanos , Masculino , Mutação , Filogenia , Falha de Tratamento , Adulto Jovem
2.
BMC Infect Dis ; 20(1): 443, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576136

RESUMO

BACKGROUND: Liangshan Yi Autonomous Prefecture is one of the areas that most severely affected by human immunodeficiency virus (HIV) in China, and virological failure on antiretroviral therapy (ART) is serious in this area. Analyses of prevalence and determinants of ART failure, the genetic diversity and drug resistance among people living with HIV (PLWH) helps improve HIV treatment efficiency and prevent HIV transmission. METHODS: A total of 5157 PLWH were recruited from 2016 to 2017. The venous blood samples were subjected to RT-PCR, followed by sequencing of the HIV-1 pol gene, targeting the protease and reverse transcriptase fragments. HIV-1 diversity was analyzed using the DNAStar software and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 2156 (41.81%) PLWH showed virological failure on ART. Males (ORm = 1.25), heterosexual behaviors and drug injection (ORm = 1.44) and mother to child transmission routes (ORm = 1.58), the clinical stage of AIDS (ORm = 1.35), having used illicit drugs and shared the needles (1-4 times: ORm = 1.34; more than 5 times: ORm = 1.52), having ever replaced ART regimen (ORm = 1.48) increased the risk of virological failure among PLWH, while higher education lever (ORm = 0.77) and ≥ 12 months on ART (12 ~ 36 months: ORm = 0.72; ≥36 months: ORm = 0.66) was associated with lower likelihood of virological failure. The data revealed that CRF07_BC (1508, 95.62%) were the most common strains, and the drug-resistant rate was 32.10% among PLWH with virological failure in this area. The high frequencies of drug resistance were found in EFV and NVP of NNRTIs, ABC, FTC and 3TC of NRTIs, and TPV/r in PIs. The most common mutations in NNRTIs, NRTIs and PIs were K103N/KN (64.69%), M184V/MV/I (36.29%) and Q58E/QE (4.93%), respectively. CONCLUSION: We concluded that surveillance of virological failure, HIV-1 subtypes, and drug resistance to understand HIV-1 epidemiology and guide modification of ART guidelines, and target prevention and control strategies should be formatted to reduce the virological failure and drug resistance to promote viral suppression and prevent HIV-1 transmission.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Variação Genética , HIV-1/genética , Grupos Minoritários , Inibidores da Transcriptase Reversa/uso terapêutico , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/transmissão , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , China/epidemiologia , Feminino , Genes pol , Humanos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Masculino , Mutação , Prevalência , Inibidores da Transcriptase Reversa/efeitos adversos , Resultado do Tratamento , Adulto Jovem
3.
Sex Transm Infect ; 96(6): 451-456, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31900319

RESUMO

OBJECTIVES: Transgender people are disproportionately affected by the HIV-1 epidemic. We evaluated the origin of HIV-1 variants carried by South American transgenders living in Milan by combining accurate phylogenetic methods and epidemiological data. METHODS: We collected 156 HIV-1 pol sequences obtained from transgender patients engaged in sex work (TSWs) followed between 1999 and 2015 at L. Sacco Hospital, Milan, Italy. Phylogenetic analyses were conducted by HIV-TRACE, MrBayes, MacClade and Beast programs. Reference sequences were retrieved from Los Alamos and local databases. Last negative testing or proxy data from clinical records of infected individuals were used to investigate the country of infection. RESULTS: Among South American TSWs, the most represented HIV-1 subtypes were B (70.5%), F1 (12.8%) and C (4.4%). Gene flow migrations of B subtype indicated significant fluxes from TSWs to Italians (21.3%) belonging to all risk groups (26.4% to heterosexuals (HEs), 18.9% to men who have sex with men (MSM), 15.1% to injecting drug users). The largest proportion of bidirectional fluxes were observed between Italians and TSWs (24.6%). For F1 subtype, bidirectional viral fluxes involved TSWs and Italians (7.1% and 14.3%), and a similar proportion of fluxes linked TSWs and Italian HEs or MSM (both 15.8%). Significant fluxes were detected from Italians to TSWs for subtype C involving both MSM (30%) and HEs (40%). Country of HIV-1 acquisition was identified for 72 subjects; overall, the largest proportion of patients with B subtype (73.5%) acquired HIV-1 infection in South America. CONCLUSIONS: Our results indicated that South American transgenders largely contribute to the heterogeneity of HIV-1 variants in our country. The high number of clusters based on all subtypes indicated numerous transmission chains in which TSWs were constantly intermixed with HEs and MSM. Our results strongly advocate interventions to facilitate prevention, diagnosis and HIV-1 care continuum among transgender people.


Assuntos
Epidemias , Genes pol/genética , Infecções por HIV/epidemiologia , HIV-1/genética , Heterossexualidade/estatística & dados numéricos , Profissionais do Sexo/estatística & dados numéricos , Pessoas Transgênero/estatística & dados numéricos , Adulto , Idoso , Feminino , Infecções por HIV/virologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Minorias Sexuais e de Gênero/estatística & dados numéricos , América do Sul/etnologia
4.
PLoS One ; 14(12): e0216515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887110

RESUMO

The HIV genome is rich in A but not G or U and deficient in C. This nucleotide bias controls HIV phenotype by determining the highly unusual composition of all major HIV proteins. The bias is also responsible for the high frequency of narrow DNA minor groove sites in the double-stranded HIV genome as compared to cellular protein coding sequences and the bulk of the human genome. Since drugs that bind in the DNA minor groove disrupt nucleosomes on sequences that contain closely spaced oligo-A tracts which are prevalent in HIV DNA because of its bias, it was of interest to determine if these drugs exert this selective inhibitory effect on HIV chromatin. To test this possibility, nucleosomes were reconstituted onto five double-stranded DNA fragments from the HIV-1 pol gene in the presence and in the absence of several minor groove binding drugs (MGBDs). The results demonstrated that the MGBDs inhibited the assembly of nucleosomes onto all of the HIV-1 segments in a manner that was proportional to the A-bias, but had no detectable effect on the formation of nucleosomes on control cloned fragments or genomic DNA from chicken and human. Nucleosomes preassembled onto HIV DNA were also preferentially destabilized by the drugs as evidenced by enhanced nuclease accessibility in physiological ionic strength and by the preferential loss of the histone octamer in hyper-physiological salt solutions. The drugs also selectively disrupted HIV-containing nucleosomes in yeast as revealed by enhanced nuclease accessibility of the in vivo assembled HIV chromatin and reductions in superhelical densities of plasmid chromatin containing HIV sequences. A comparison of these results to the density of A-tracts in the HIV genome indicates that a large fraction of the nucleosomes that make up HIV chromatin should be preferred in vitro targets for the MGBDs. These results show that the MGBDs preferentially disrupt HIV-1 chromatin in vitro and in vivo and raise the possibility that non-toxic derivatives of certain MGBDs might serve as a novel class of anti-HIV agents.


Assuntos
Cromatina/efeitos dos fármacos , Cromatina/genética , HIV/genética , Sequência de Bases , Sítios de Ligação/genética , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina , Biologia Computacional/métodos , DNA/efeitos dos fármacos , DNA/genética , Genes pol/genética , HIV/metabolismo , Infecções por HIV/genética , Humanos
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(8): 982-987, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31484265

RESUMO

Objective: To understand the distribution of HIV-1 genotypes and the status of drug resistance among people living with HIV who had prepared to initiate antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture (Dehong). Methods: A total of 170 adults with HIV were recruited in Dehong from January to June 2017, before initiating ART. HIV-1 pol genes were amplified and used to analyze the HIV-1 genotypes and drug resistance. Results: A total of 147 samples were successfully sequenced. Based on the phylogenetic analysis, 12 HIV-1 genotypes were found among the subjects, including three predominant genotypes such as subtype C (29.9%, 44/147), unique recombinant forms (URFs) (27.2%, 40/147) and CRF01_AE (19.7%, 29/147). Circulating recombinant forms (CRFs) which were newly identified in this area in recent years were also found among these subjects, including CRF62_BC, CRF64_BC, CRF86_BC and CRF96_cpx. The distribution of HIV-1 genotypes between heterosexual transmission or intravenous drug use, showed statistical difference. Surveillance drug resistance mutations (SDRMs) were found among 8.8% (13/147) of the subjects. Proportion of drug resistant strains among injecting drug users (25.0%, 8/32) was higher than that among those heterosexual transmitted individuals (4.6%, 5/109, χ(2)=10.166, P=0.002). Conclusions: Among people living with HIV-1 who had prepared to initiate ART, their HIV-1 genetics were highly complicated, with moderate prevalence rate of HIV-1 drug-resistant strains.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , Adulto , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade , China/epidemiologia , Genes pol , Genótipo , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , Humanos , Filogenia
6.
PLoS One ; 14(9): e0221879, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31479466

RESUMO

BACKGROUND: The World Health Organization (WHO) recommends a method to estimate nationally representative pretreatment HIV drug resistance (PDR) in order to evaluate the effectiveness of first -line treatments. The objective of the present study was to determine the prevalence of PDR in Cuban adults infected with HIV-1. MATERIALS AND METHODS: A cross-sectional study in Cuban adults infected with HIV-1 over 18 years was conducted. The probability proportional to size method for the selection of municipalities and patients without a prior history of antiretroviral treatment during the period from January 2017 to June 2017 was used. The plasma from 141 patients from 15 municipalities for the determination of viral subtype and HIV drug resistance was collected. Some clinical and epidemiological variables were evaluated. RESULTS: 80. 9% of the patients corresponded to the male sex and 76.3% were men who have sex with other men (MSM). The median CD4 count was 371 cells / mm3 and the median viral load was 68000 copies / mL. The predominant genetic variants were subtype B (26.9%), CRF19_cpx (24.1%), CRF 20, 23, 24_BG (23.4%) and CRF18_cpx (12%). Overall, the prevalence of PDR was 29.8% (95%, CI 22.3-38.1). The prevalence was 12.8% (95%, CI 6.07-16.9) for any nucleoside reverse transcriptase inhibitor (NRTI), 23.4% (95%, CI 16.7-31.3) for any non-reverse transcriptase inhibitor (NNRTI) and 1.4% (95%, CI 0.17-5.03) for any protease inhibitor (PI). The most frequent mutations detected were K103N (12.9%), G190A (6.4%) and Y181C (4.8%). CONCLUSIONS: The NNRTI prevalence above 10% in our study indicates that the first-line antiretroviral therapy in Cuba may be less effective and supports the need to look for new treatment options that contribute to therapeutic success and help the country achieve the global goals 90-90-90 set forth by UNAIDS.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1 , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Estudos Transversais , Cuba/epidemiologia , Farmacorresistência Viral/genética , Feminino , Genes pol , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Prevalência , Adulto Jovem
7.
Virol J ; 16(1): 103, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416460

RESUMO

BACKGROUND: The high genetic diversity of HIV-1 has been shown to influence the global distribution, disease progression, treatment success, and the development of an effective vaccine. Despite the low HIV prevalence in Cameroon, all the major HIV subtypes alongside several circulating recombinant forms (CRFs) and unique recombinant forms (URFs) have been reported in Cameroon. To date, HIV-1 diversity in some parts of Cameroon has been largely studied however, information on circulating HIV-1 subtypes in the Northwest region (NWR) of Cameroon is dearth. Therefore the aim of this study was to determine the current circulating HIV-1 subtypes among adults in the NWR of Cameroon. METHODS: The genetic analysis of the reverse transcriptase region of the pol gene was performed on 81 samples. The samples were collected from drug naïve patients aged between 18 and 61 years residing within the rural and urban towns in the NWR during the period between February and April 2016. Viral RNA was extracted from plasma, reverse-transcribed, further amplified by nested-PCR before sequencing using an in-house protocol. Generated sequences were then phylogenetically analyzed together with references using MEGA 7. RESULTS: Phylogenetic analysis revealed a broad viral diversity including CRF02 _AG (74.1%), F2 (7.4%), D (7.4%), G (3.7%), A1 (1.2%), CRF22_01A1 (2.5%), CRF06_cpx (1.2%), CRF09_cpx (1.2%), CRF11_cpx (1.2%). Three close epidemic clusters were found among F2 (1) and CRF02_AG (2) variants. For the first time we are reporting the CRF22_01A1 subtype in this region. CONCLUSION: Our findings update HIV-1 subtypes information in Cameroon and uphold previous studies that CRF02_AG is the most prevalent subtype. This CRF02_AG subtype may have important public health, research, and clinical consequences.


Assuntos
Variação Genética , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , Filogenia , Adolescente , Adulto , Camarões/epidemiologia , Estudos Transversais , Evolução Molecular , Feminino , Genes pol , Genótipo , Geografia , HIV-1/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , DNA Polimerase Dirigida por RNA/genética , Recombinação Genética , Análise de Sequência de DNA , Adulto Jovem
8.
Cells ; 8(8)2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443253

RESUMO

HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed.


Assuntos
Genes env/genética , Genes pol/genética , Infecções por HIV , HIV-1 , RNA Viral/sangue , Adulto , Feminino , Infecções por HIV/sangue , Infecções por HIV/líquido cefalorraquidiano , HIV-1/genética , HIV-1/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Análise de Sequência de RNA , Replicação Viral , Adulto Jovem
9.
Virol J ; 16(1): 83, 2019 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-31228958

RESUMO

BACKGROUND: Shenzhen City is a rapidly growing area with a large number of floating populations, thus making it difficult to control HIV. Serial cross-sectional studies are helpful for the prediction of epidemiological tendency. In this study, two parallel cross-sectional studies were compared to explore changes in HIV epidemiology in Shenzhen, China. METHODS: Two hundred and fifty newly reported HIV-positive cases were randomly selected in Shenzhen City in 2013 and 2015. Socio-demographical information was collected with informed consent. Full-length gag and partial pol genes were amplified using nested RT-PCR followed by sequencing and phylogenetic analysis. The genotypes of anti-HIV drug resistance were also analyzed. The characteristics of the HIV epidemics of 2013 and 2015 were compared to identify patterns. RESULTS: The proportion of single, young MSMs dramatically increased in 2015 compared to 2013. Many subtypes, including CRF07_BC (36.4%), CRF01_AE (34.1%), CRF55_01B (10.2%), B (6.4%), CRF08_BC (3.4%), CRF59_01B (0.9%), C (0.7%), D (0.2%), CRF68_01B (0.2%), CRF67_01B (0.2%), and unique recombinant forms (URFs, 7.3%), were identified. Close phylogenetic relationships between strains prevalent in Shenzhen and other areas of China was observed. No epidemic cluster confined to single, young MSMs was identified. 0.4 and 2.8% of the strains contained transmitted drug-resistant mutations in 2013 and 2015, respectively. CONCLUSION: Although the interval period is short, changes in HIV epidemiology in Shenzhen City are distinct. Frequent surveillance of HIV epidemics in Shenzhen City is thus necessary. Single, young MSMs have become a high-risk population for HIV infection and should be considered as focus population for HIV prevention and behavior intervention in Shenzhen City.


Assuntos
Infecções por HIV/epidemiologia , HIV-1/genética , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Farmacorresistência Viral , Genes gag/genética , Genes pol/genética , Genótipo , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase , RNA Viral/genética , Fatores de Risco , Análise de Sequência de DNA , Adulto Jovem
10.
Intervirology ; 62(1): 9-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31104062

RESUMO

OBJECTIVE: The human endogenous retroviruses (HERVs) are endogenous retroviruses that were inserted into the germ cell DNA of humans over 30 million years ago. Insertion of HERVs into the chromosomal DNA can influence a number of host genes in various modes during human evolution and their proviral long terminal repeats can participate in the transcriptional regulation of various cellular genes. Our aim was to evaluate the pol gene expression of HERV-K and HERV-H in mesenchymal stem cells (MSCs) in relation with the expression of stemness genes such as NANOG, OCT-4, and SOX-2. METHODS: MSCs were isolated from bone marrow of healthy donors and expanded until the 5th passage in α-MEM with 10% fetal bovine serum. HERV-K, HERV-H pol gene, NANOG, OCT-4, SOX-2, and GAPDH expression was quantified by real-time PCR in MSCs during the expansion. RESULTS: HERV-K and HERV-H expression was always higher at p1 compared to other passages and this difference reached a high statistical significance when passage p1 was compared with passage 3. In addition, NANOG, OCT-4, and SOX-2 expression at p1 was significantly higher than their expression at p3. Pearson's test demonstrated a strong correlation between the expression of HERV-K and HERV-H and the expression of NANOG, OCT-4, and SOX-2. CONCLUSIONS: Our findings showed that HERV-K and H were concurrently expressed with pluripotency biomarkers NANOG, OCT-4, and SOX-2.


Assuntos
Retrovirus Endógenos/genética , Expressão Gênica , Genes pol , Células-Tronco Mesenquimais/virologia , Biomarcadores , Humanos , Proteína Homeobox Nanog/genética , Fator 3 de Transcrição de Octâmero/genética , Fatores de Transcrição SOXB1/genética
11.
BMC Infect Dis ; 19(1): 313, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961560

RESUMO

BACKGROUND: Genetic variability and liability to develop drug-resistant mutations are the main characteristics of HIV-1, which can not only increase the risk of antiretroviral treatment (ART) failure, but also can lead to the spread of resistant strains. We aim to investigate the distribution of HIV-1 genotypes and prevalence of pretreatment drug resistance (PDR) in ART-naïve HIV-1 infected patients in Shanghai China. METHODS: A cross-sectional study was performed among the newly diagnosed ART-naive HIV-1 infected patients during the period from January 2017 to November 2017 in Shanghai Public Health Clinical Center. The target fragment of 1316 bp in the pol gene spanning the reverse transcriptase and protease regions was amplified using a nested polymerase chain reaction. HIV-1 genotypes were determined by phylogenetic analysis, and PDR associated mutations were determined according to Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/ ). RESULTS: We successfully amplified pol gene sequences from blood samples of 317 patients, of whom 95.3% were male, and 68.8% were men who have sex with men. The median age was 33 years; and the median CD4 count was 275 cells/µL. The predominant HIV-1 genotype was circulating recombinant form (CRF) 01_AE (53.0%, 168/317), followed by CRF07_BC (29.7%, 94/317), B (7.6%, 24/317), CRF08_BC (1.9%, 6/317), CRF55_01B (1.9%, 6/317), CRF 59_01B (0.9%, 3/317). In addition, 5% (16/317) HIV-1 strains were identified as other subtypes or CRFs/URFs (unique recombinant forms). The overall prevalence of PDR was 17.4% (55/317). PDR frequency to non-nucleoside reverse transcriptase inhibitor (NNRTI, 16.4%) was much higher than that to nucleoside reverse transcriptase inhibitor (NRTI, 4.7%) and protease inhibitor (PI, 0.6%). The most common HIV-1 mutation pattern for NNRTI and NRTI were V179D/E (10.1%, 32/317) and M184 V (2.8%, 9/317), respectively. About half (49.1%, 27/55) of the HIV-1 strains with mutation presented as potential low-level resistant to NNRTI attributed to V179D/E. CONCLUSION: The distribution of HIV-1 genotypes in Shanghai China is diverse and complex. The high prevalence of PDR highlights the significance of baseline HIV-1 drug resistance testing. Non-NNRTI-containing regimen may be the preferred initial therapy for newly diagnosed HIV-1 patients in Shanghai in the absence of PDR test results.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/genética , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Genes pol , Variação Genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Prevalência
12.
Virus Res ; 266: 43-47, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30951792

RESUMO

In 1936, John Joseph Bittner identified mouse mammary tumor virus (MMTV), a milk transmitted beta retrovirus, a form of single-stranded positive-sense RNA virus. A retrovirus inserts a copy of its genome into the DNA of a host cell, thus altering the cell's genome. In the current analysis, we searched for MMTV sequences within the human genome. To compare the MMTV genome to the human genome, we used BLAT, the Blast-Like Alignment Tool of the UCSC Genome Browser. BLAT can align a user sequence of 25 bases or more to the genome. 60 MMTV sequences were in the human genome. Of 56 sequences from the MMTV POL gene, 36 POL sequences were from the same part of the gene, beginning at viral nucleotide 4800 but of different lengths. 8 viral sequences began at nucleotide ∼3430 of the POL gene. Four viral sequences were from GAGdUTPase, encoded by the MMTV PRO gene. Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is an enzyme present in several major retroviral families. In MMTV dUTPase may be essential for viral replication. Since BLAT identified no MMTV envelope (env) sequence in the human genome, the env sequences from breast tumors and normal breast tissue found in other studies may have come from an MMTV infection. However, no one is certain how MMTV could enter human cells, since the cells do not have a cellular receptor for MMTV, as do mouse cells.


Assuntos
Neoplasias da Mama/virologia , Mama/virologia , Genes env/genética , Vírus do Tumor Mamário do Camundongo/genética , Sequência de Bases , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Bases de Dados Genéticas , Feminino , Genes pol/genética , Genoma Humano/genética , Humanos , Pirofosfatases/genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Software
13.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(2): 196-201, 2019 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-30744272

RESUMO

Objective: To understand the prevalence of drug resistance in treatment-naive injecting drug users (IDUs) infected with HIV-1 in Guangzhou. Methods: HIV-1 RNA were extracted from the serum specimens of the newly confirmed HIV-1 positive IDUs living in Guangzhou, being infected through injecting drug use and receiving no antiretroviral therapy at the time of confirmation during 2008-2015. Full sequence of pol protease (PR) gene and partial sequence of reverse transcriptase (RT) gene were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and sequenced. After that, data were submitted to the HIV resistance database of Stanford University for drug resistance analysis. Results: Among the 518 HIV-1 infected IDUs, HIV-1pol gene segments were successfully obtained from the serum samples of 407 HIV-1 infected IDUs (78.57%) aged 18-64 (37.44±8.14) years. Among them, males accounted for 89.68% (365/407), those of Han ethnic group accounted for 89.93% (366/407), the unmarried accounted for 55.28% (225/407), and those with education level of junior high school or below accounted for 83.78% (341/407). The distribution of subtypes was predominated by CRF07_BC (47.18%, 192/407), followed by CRF01_AE (23.83%, 97/407), CRF08_BC (22.85%, 93/407), and other subtypes (6.14%, 25/407). The overall prevalence of drug resistance was 3.44% (14/407). The prevalence of drug resistance to protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors were 1.47%(6/407), 0.25% (1/407) and 1.72% (7/407) respectively. The mutation rate was 12.29% (50/407). No major drug resistance mutation was detected in protease and nucleoside reverse transcriptase regions. Higher rate of V179E mutation in the non-nucleoside reverse transcriptase region was detected in other subtypes and subtype CRF07_BC. Mutation seemed to have occurred in all 8 cases of subtype CRF55_01B in other subtypes. The highest mutation rate of E138A was detected in subtype CRF08_BC (3.23%). Two cases were resistant to all four drugs of NNRTIs. Conclusions: The prevalence of drug resistance in treatment-naive HIV-1 positive IDUs remained at a relatively low level during 2008-2015, in Guangzhou. Most infections were sensitive to existing antiviral drugs. However, drug resistance surveillance in IDUs infected with HIV should be strengthened to prevent the prevalence of multi-drug resistance and cross drug resistance.


Assuntos
Farmacorresistência Viral/genética , Usuários de Drogas , Infecções por HIV/tratamento farmacológico , HIV-1/genética , RNA Viral/genética , Adolescente , Adulto , Criança , Genes pol/genética , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/etnologia , Infecções por HIV/psicologia , HIV-1/isolamento & purificação , Humanos , Masculino , Mutação , Prevalência , RNA Viral/efeitos dos fármacos , Adulto Jovem
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(2): 202-206, 2019 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-30744273

RESUMO

Objective: To understand the epidemiological characteristics of one large HIV molecular transmission cluster in Jiaxing city, Zhejiang province, 2017 in order to select those people under high-risk and providing basis for programs on prevention. Methods: During 2017, newly diagnosed HIV/AIDS cases in this city were recruited. Plasma samples were collected from subjects, followed by RNA extraction, RT-PCR and nest-PCR for pol gene amplification, before being sequenced and aligned. Mega 6.0 software was used to construct phylogenetic tree, and Cytoscape 3.6.0 software was used to identify HIV molecular transmission clusters. Cases within the large transmission clusters were investigated, using a field-epidemiology-questionnaire. Data related to socio-demographics and previous sexual behaviors were collected and EpiData 3.0 and SPSS 20.0 software were used. Results: In the large transmission cluster with subtype identified as CRF07_BC, in Jiaxing, 2017, 26 cases of the total 30 cases were investigated. A total of 80.8% (21/26) could be identified as newly infected within the last two years and 30.8%(8/26) could be identified as newly infected within the last one year, including 22 cases infected locally. Among several infected cases who were at age 45 years or older, they admitted that they had experienced unprotected sexual contacts in local city for long time and having had more than 10 disclosed sexual contacts within the last two years at the local venues. Conclusions: This molecular cluster had been formed and scaled up quickly in recent two years, it has played an important role in promoting and scaling up the HIV transmission. Three cases identificed as high risk played an importantrde role in scaling up this cluster.


Assuntos
Genes pol , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/classificação , HIV-1/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , China/epidemiologia , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/genética , HIV-1/isolamento & purificação , Humanos , Epidemiologia Molecular , Filogenia , Reação em Cadeia da Polimerase , RNA Viral/sangue , Comportamento Sexual , Produtos do Gene pol do Vírus da Imunodeficiência Humana
15.
Sci Data ; 5: 180148, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-30063225

RESUMO

Accurate classification of HIV-1 group M lineages, henceforth referred to as subtyping, is essential for understanding global HIV-1 molecular epidemiology. Because most HIV-1 sequencing is done for genotypic resistance testing pol gene, we sought to develop a set of geographically-stratified pol sequences that represent HIV-1 group M sequence diversity. Representative pol sequences differ from representative complete genome sequences because not all CRFs have pol recombination points and because complete genome sequences may not faithfully reflect HIV-1 pol diversity. We developed a software pipeline that compiled 6,034 one-per-person complete HIV-1 pol sequences annotated by country and year belonging to 11 pure subtypes and 70 CRFs and selected a set of sequences whose average distance to the remaining sequences is minimized for each subtype/CRF and country to generate a Geographically-Stratified set of 716 Pol Subtype/CRF (GSPS) reference sequences. We provide extensive data on pol diversity within each subtype/CRF and country combination. The GSPS reference set will also be useful for HIV-1 pol subtyping.


Assuntos
Genes pol , Infecções por HIV/virologia , HIV-1/genética , Infecções por HIV/epidemiologia , HIV-1/classificação , Humanos , Epidemiologia Molecular , Recombinação Genética
16.
BMC Biol ; 16(1): 75, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29996827

RESUMO

BACKGROUND: RNA-guided CRISPR/Cas9 systems can be designed to mutate or excise the integrated HIV genome from latently infected cells and have therefore been proposed as a curative approach for HIV. However, most studies to date have focused on molecular clones with ideal target site recognition and do not account for target site variability observed within and between patients. For clinical success and broad applicability, guide RNA (gRNA) selection must account for circulating strain diversity and incorporate the within-host diversity of HIV. RESULTS: We identified a set of gRNAs targeting HIV LTR, gag, and pol using publicly available sequences for these genes and ranked gRNAs according to global conservation across HIV-1 group M and within subtypes A-C. By considering paired and triplet combinations of gRNAs, we found triplet sets of target sites such that at least one of the gRNAs in the set was present in over 98% of all globally available sequences. We then selected 59 gRNAs from our list of highly conserved LTR target sites and evaluated in vitro activity using a loss-of-function LTR-GFP fusion reporter. We achieved efficient GFP knockdown with multiple gRNAs and found clustering of highly active gRNA target sites near the middle of the LTR. Using published deep-sequence data from HIV-infected patients, we found that globally conserved sites also had greater within-host target conservation. Lastly, we developed a mathematical model based on varying distributions of within-host HIV sequence diversity and enzyme efficacy. We used the model to estimate the number of doses required to deplete the latent reservoir and achieve functional cure thresholds. Our modeling results highlight the importance of within-host target site conservation. While increased doses may overcome low target cleavage efficiency, inadequate targeting of rare strains is predicted to lead to rebound upon cART cessation even with many doses. CONCLUSIONS: Target site selection must account for global and within host viral genetic diversity. Globally conserved target sites are good starting points for design, but multiplexing is essential for depleting quasispecies and preventing viral load rebound upon therapy cessation.


Assuntos
Sistemas CRISPR-Cas/genética , Produtos do Gene gag/genética , Genes pol , Repetição Terminal Longa de HIV/genética , HIV-1/genética , RNA Guia , Edição de Genes , Terapia Genética , Variação Genética , Infecções por HIV/terapia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Latência Viral
17.
PLoS One ; 13(7): e0198999, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29975689

RESUMO

BACKGROUND: South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa. METHODS: Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13-20 years (Mpumalanga province, 2011-2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software. RESULTS: The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6-7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2-6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931-1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3-2.81x10-3) per site per year. CONCLUSIONS: Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial.


Assuntos
Genes pol/genética , Infecções por HIV/genética , HIV-1/genética , Filogenia , Adolescente , Adulto , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , HIV-1/patogenicidade , Humanos , Epidemiologia Molecular , África do Sul/epidemiologia , Adulto Jovem
18.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(5): 619-624, 2018 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-29860805

RESUMO

Objective: To understand prevalence and transmission of transmitted drug resistance (TDR) among HIV infected men who have sex with men (MSM) in Tianjin from 2014 to 2017. Methods: A total of 225 blood samples were collected from HIV infected MSM in Tianjin from 2014 to 2017. Pol gene fragments were obtained by viral RNA extraction and nested PCR amplification. Phylogenetic and drug resistance analyses were conducted. Results: A total of 205 samples were successfully sequenced and analyzed. Based on pol sequences, 53.2% (109/205), 28.8% (59/205), 10.2% (21/205), 4.9% (10/205) and 2.9% (6/205) of the samples were positive for HIV subtypes CRF01_AE, CRF07_BC, B, CRF55_01B and unique recombinant forms (URFs). Twenty transmission clusters, including 75 sequences, were identified and 62.5% (10/16) of sequences with TDR were in 5 clusters. The prevalence of TDR was 7.8% between 2014 and 2017. The annual prevalence rate increased from 3.9% (2/51) in 2014, 5.7% (3/53) in 2015, 9.6% (5/52) in 2016 to 12.2%(6/49) in 2017, the difference was not significant (χ(2)=2.504, P=0.127). CRF01_AE and B strains had high TDR prevalence (3.4%, 7/205) and (2.9%, 6/205), respectively. The TDR mutation was mainly NNRTIs, the TDR prevalence was 6.3% (13/205). In contract, the TDR prevalence of NRTIs and PIs were 1.5% (3/205) and 1.0% (2/205) respectively. Conclusion: Results from this study suggested that the prevalence of HIV-1 TDR strains in MSM was serious in Tianjin. It is necessary to take effective prevention and control measures.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , Soropositividade para HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/genética , Homossexualidade Masculina/etnologia , RNA Viral/genética , China , Genes pol , Genótipo , Infecções por HIV/sangue , Infecções por HIV/etnologia , Transcriptase Reversa do HIV/genética , Soropositividade para HIV/etnologia , HIV-1/isolamento & purificação , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Mutação , Filogenia , Reação em Cadeia da Polimerase , Prevalência , RNA Viral/efeitos dos fármacos , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(5): 678-681, 2018 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-29860817

RESUMO

Objective: To explore distribution of HIV gene subtypes among newly reported HIV/AIDS cases from China and Myanmar in Dehong Dai and Jingpo prefecture of Yunnan province in 2016. Methods: We conducted DNA extractions from newly reported HIV/AIDS cases in 2016. The gag, env and pol genes were amplified by using reverse transcription-PCR (RT-PCR) and sequenced to identify HIV subtypes. Results: A total of 1 112 newly diagnosed HIV cases were reported in Dehong in 2016, and the HIV subtypes were identified for 860 cases. Subtype C was predominant (33.6%), followed by unique recombinant forms (URFs) (28.4%), CRF01_AE (18.6%) and so on. URFs include four recombination, among which the recombination of CRF01_AE and C subtype were predominant. The HIV subtype distribution was associated with nationality and transmission route in HIV/AIDS cases from Myanmar. Conclusions: The gene subtypes of C, URFs and CRF01_AE were mainly distributed; distribution of URFs remained complex and diverse among newly reported HIV/AIDS cases in Dehong in 2016.


Assuntos
Grupos Étnicos/genética , Genes pol , Infecções por HIV/diagnóstico , HIV-1/genética , Reação em Cadeia da Polimerase/métodos , Sequência de Bases , China/epidemiologia , Genótipo , Infecções por HIV/etnologia , Infecções por HIV/genética , Humanos , Masculino , Filogenia , Sorogrupo
20.
Emerg Microbes Infect ; 7(1): 117, 2018 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-29946141

RESUMO

The avian leukosis virus subgroup K (ALV-K), a novel subgroup in Chinese indigenous chicken breeds, has been difficult to isolate in the past due to its poor replication ability. However, according to the latest monitoring data, the replication ability and isolation rate of ALV-K have clearly increased, and new strains with mutations in the pol gene have also been found. To determine the effects of such mutations on the biological characteristics of ALV-K, a pair of infectious clones were constructed and rescued. The first virus was an ALV-K Chinese isolate with mutations in its pol gene, named rSDAUAK-11. The second virus was a recuperative rSDAUAK-11 from which mutations in the pol gene were recovered according to the corresponding region of the ALV-K prototype virus JS11C1, named rRSDAUAK-11. In addition, two quantitative real-time polymerase chain reaction assays were developed to specifically detect these virus strains. Using such methods, we observed a marked improvement of the reverse transcriptase activity, replication ability and vertical transmission ability of rSDAUAK-11, which also revealed a formidable competitive advantage in mixed infection with rRSDAUAK-11 and corresponded to the differences between the wild strains SDAUAK-11 and JS11C1. Accordingly, our findings not only show that mutations in the pol gene are an important molecular mechanism contributing to corresponding changes in the biological characteristics of the newest ALV-K but also emphasize the potential future eradication of ALV.


Assuntos
Vírus da Leucose Aviária/fisiologia , Leucose Aviária/virologia , Galinhas/virologia , Genes pol , Mutação , Replicação Viral , Animais , Leucose Aviária/transmissão , Vírus da Leucose Aviária/isolamento & purificação , Análise Mutacional de DNA , Genoma Viral , Instabilidade Genômica , Transmissão Vertical de Doença Infecciosa
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