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1.
Kim Tien Ng Kah Ying Ng Wei Xin Khong Kuan Kiat Chew Palvinder Kaur Singh Joe Kwan Yap Mei Ting Tan Yee Sin Leo Oliver Laeyendecker Thomas C. Quinn Adeeba Kamarulzaman Kok Keng Tee Oon Tek Ng 《PloS one》2013,8(12)
HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 – 2629), gp120 (HXB2: 6942 – 7577) and gp41 (HXB2: 7803 – 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 – 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore. 相似文献
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Virologica Sinica - Laos is the only landlocked country in Southeast Asia and borders Thailand, Myanmar and Cambodia, the three countries in this region that have been hardest hit by human... 相似文献
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Wei Zhen Chow Haider Al-Darraji Yeat Mei Lee Yutaka Takebe Adeeba Kamarulzaman Kok Keng Tee 《Journal of virology》2012,86(20):11398-11399
A novel HIV-1 genotype designated CRF53_01B was recently characterized from three epidemiologically unrelated persons in Malaysia. Here we announced three recently isolated full-length genomes of CRF53_01B, which is likely to be phylogenetically linked to CRF33_01B, circulating widely in Southeast Asia. The genome sequences may contribute to HIV-1 molecular surveillance and future vaccine development in the region. 相似文献
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Kok Keng Tee Shigeru Kusagawa Xiao-Jie Li Narumi Onogi Maya Isogai Saiki Hase Rie Uenishi Huanan Liao Adeeba Kamarulzaman Yutaka Takebe 《PloS one》2009,4(8)
A growing number of emerging HIV-1 recombinants classified as circulating recombinant forms (CRFs) have been identified in Southeast Asia in recent years, establishing a molecular diversity of increasing complexity in the region. Here, we constructed a replication-competent HIV-1 clone for CRF33_01B (designated p05MYKL045.1), a newly identified recombinant comprised of CRF01_AE and subtype B. p05MYKL045.1 was reconstituted by cloning of the near full-length HIV-1 sequence from a newly-diagnosed individual presumably infected heterosexually in Kuala Lumpur, Malaysia. The chimeric clone, which contains the 5′ LTR (long terminal repeat) region of p93JP-NH1 (a previously isolated CRF01_AE infectious clone), showed robust viral replication in the human peripheral blood mononuclear cells. This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus. Viral propagation, however, was not detected in various human T cell lines including MT-2, M8166, Sup-T1, H9, Jurkat, Molt-4 and PM1. p05MYKL045.1 appears to proliferate only in restricted host range, suggesting that unknown viral and/or cellular host factors may play a role in viral infectivity and replication in human T cell lines. Availability of a CRF33_01B molecular clone will be useful in facilitating the development of vaccine candidates that match the HIV-1 strains circulating in Southeast Asia. 相似文献
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George K. Hightower Susanne J. May Josué Pérez-Santiago Mary E. Pacold Gabriel A. Wagner Susan J. Little Douglas D. Richman Sanjay R. Mehta Davey M. Smith Sergei L. Kosakovsky Pond 《PloS one》2013,8(6)
Objective
Characterize intra-individual HIV-1 subtype B pol evolution in antiretroviral naive individuals.Design
Longitudinal cohort study of individuals enrolled during primary infection.Methods
Eligible individuals were antiretroviral naïve participants enrolled in the cohort from December 1997-December 2005 and having at least two blood samples available with the first one collected within a year of their estimated date of infection. Population-based pol sequences were generated from collected blood samples and analyzed for genetic divergence over time in respect to dual infection status, HLA, CD4 count and viral load.Results
93 participants were observed for a median of 1.8 years (Mean = 2.2 years, SD = 1.9 years). All participants classified as mono-infected had less than 0.7% divergence between any two of their pol sequences using the Tamura-Nei model (TN93), while individuals with dual infection had up to 7.0% divergence. The global substitution rates (substitutions/nucleotide/year) for mono and dually infected individuals were significantly different (p<0.001); however, substitution rates were not associated with HLA haplotype, CD4 or viral load.Conclusions
Even after a maximum of almost 9 years of follow-up, all mono-infected participants had less than 1% divergence between baseline and longitudinal sequences, while participants with dual infection had 10 times greater divergence. These data support the use of HIV-1 pol sequence data to evaluate transmission events, networks and HIV-1 dual infection. 相似文献7.
Boonchawalit S Jullaksorn D Uttiyoung J Yowang A Krathong N Chautrakul S Yamashita A Ikuta K Roobsoong A Kanitvittaya S Sawanpanyalert P Kameoka M 《PloS one》2011,6(11):e27098
Background
The envelope glycoproteins (Env), gp120 and gp41, are the most variable proteins of human immunodeficiency virus type 1 (HIV-1), and are the major targets of humoral immune responses against HIV-1. A circulating recombinant form of HIV-1, CRF01_AE, is prevalent throughout Southeast Asia; however, only limited information regarding the immunological characteristics of CRF01_AE Env is currently available. In this study, we attempted to examine the evolutionary pattern of CRF01_AE Env under the selection pressure of host immune responses.Methodology/Principal Findings
Peripheral blood samples were collected periodically over 3 years from 15 HIV-1-infected individuals residing in northern Thailand, and amplified env genes from the samples were subjected to computational analysis. The V5 region of gp120 showed highest variability in several samples over 3 years, whereas the V1/V2 and/or V4 regions of gp120 also showed high variability in many samples. In addition, the N-terminal part of the C3 region of gp120 showed highest amino acid diversity among the conserved regions of gp120. Chronological changes in the numbers of amino acid residues in gp120 variable regions and potential N-linked glycosylation (PNLG) sites are involved in increasing the variability of Env gp120. Furthermore, the C3 region contained several amino acid residues potentially under positive selection, and APOBEC3 family protein-mediated G to A mutations were frequently detected in such residues.Conclusions/Significance
Several factors, including amino acid substitutions particularly in gp120 C3 and V5 regions as well as changes in the number of PNLG sites and in the length of gp120 variable regions, were revealed to be involved in the molecular evolution of CRF01_AE Env. In addition, a similar tendency was observed between CRF01_AE and subtype C Env with regard to the amino acid variation of gp120 V3 and C3 regions. These results may provide important information for understanding the immunological characteristics of CRF01_AE Env. 相似文献8.
Kim Tien Ng Lai Yee Ong Yutaka Takebe Adeeba Kamarulzaman Kok Keng Tee 《Journal of virology》2012,86(20):11405-11406
We report here the first novel HIV-1 circulating recombinant form (CRF) 54_01B (CRF54_01B) isolated from three epidemiologically unlinked subjects of different risk groups in Malaysia. These recently sampled recombinants showed a complex genome organization composed of parental subtype B′ and CRF01_AE, with identical recombination breakpoints observed in the gag, pol, and vif genes. Such a discovery highlights the ongoing active generation and spread of intersubtype recombinants involving the subtype B′ and CRF01_AE lineages and indicates the potential of the new CRF in bridging HIV-1 transmission among different risk groups in Southeast Asia. 相似文献
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Justine K. Wong Grant R. Campbell Stephen A. Spector 《The Journal of biological chemistry》2010,285(24):18319-18325
The clade B human immunodeficiency virus, type 1 (HIV-1) Tat (trans-acting regulatory protein) induces interleukin-10 (IL-10) production in monocytes. IL-10, an anti-inflammatory cytokine, down-regulates proinflammatory cytokines and suppresses the immune response, leading to a rapid progression from HIV-1 infection to AIDS. Nine clades of HIV-1 are responsible for the majority of infections worldwide. Recent studies demonstrate that different HIV-1 clades have biological differences in relation to transmission, replication, and disease progression. In this study, we show that the cysteine to serine mutation at position 31, found in >90% of HIV-1 clade C Tat proteins, results in a marked decrease in IL-10 production in monocytes compared with clade B Tat. Additionally, the C31S mutation found in C Tat is responsible for the inability of these Tat proteins to produce high IL-10 levels in monocytes due to its inability to induce intracellular calcium flux through L-type calcium channels. Moreover, we show that p38α/p38β and phosphoinositide 3-kinase are crucial to Tat-induced IL-10 production. These findings provide further evidence that HIV-1 clades differ in their biological properties that may impact HIV-1 pathogenesis and disease progression. 相似文献
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Background
The B′, CRF07_BC and CRF01_AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China.Methodology/Principal Findings
The baseline susceptibility of 14 representative HIV-1 isolates (5 CRF07_BC, 4 CRF01_AE, and 5 B′), most of which were R5 viruses, obtained from drug-naïve patients to HIV entry inhibitors, including two fusion inhibitors (enfuvirtide and C34), two CCR5 antagonists (maraviroc and TAK779) and one CXCR4 antagonist (AMD3100), were determined by virus inhibition assay. The sequences of their env genes were amplified and analyzed. These isolates possessed similar susceptibility to C34, but they exhibited different sensitivity to enfuvirtide, maraviroc or TAK779. CRF07_BC isolates, which carried polymorphisms of A578T and V583I in the N-terminal heptad repeat and E630Q, E662A, K665S, A667K and S668N in the C-terminal heptad repeat of gp41, were about 5-fold less sensitive than B′ and CRF01_AE isolates to enfuvirtide. Subtype B′ isolates with a unique polymorphism site of F317W in V3 loop, were about 4- to 5-fold more sensitive than CRF07_BC and CRF01_AE isolates to maraviroc and TAK779. AMD3100 at the concentration as high as 5 µM exhibited no significant inhibitory activity against any of the isolates tested.Conclusion
Our results suggest that there are significant differences in baseline susceptibility to HIV entry inhibitors among the predominant HIV-1 subtypes in China and the differences may partly result from the naturally occurring polymorphisms in these subtypes. This study provides useful information for rational design of optimal therapeutic regimens for HIV-1-infected patients in China. 相似文献11.
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Kim Tien Ng Lai Yee Ong Sin How Lim Yutaka Takebe Adeeba Kamarulzaman Kok Keng Tee 《PloS one》2013,8(6)
HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253–3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2–7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion. 相似文献
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Lavinia Fabeni Claudia Alteri Nicoletta Orchi Caterina Gori Ada Bertoli Federica Forbici Francesco Montella Alfredo Pennica Gabriella De Carli Massimo Giuliani Fabio Continenza Carmela Pinnetti Emanuele Nicastri Francesca Ceccherini-Silberstein Claudio Maria Mastroianni Enrico Girardi Massimo Andreoni Andrea Antinori Maria Mercedes Santoro Carlo Federico Perno 《PloS one》2015,10(8)
Background
Increased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B-subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy).Methods
Pol and V3 sequences were available at the time of diagnosis for all individuals. Maximum-Likelihood and Bayesian phylogenetic-trees with bootstrap and Bayesian-probability supports defined transmission-clusters. HIV-1 drug-resistance and V3-tropism were also evaluated.Results
Among 534 new HIV-1 non-B cases, diagnosed from 2011 to 2014, in Central-Italy, 35 carried virus gathering in two distinct clusters, including 27 HIV-1 C and 8 CRF17_BF subtypes, respectively. Both clusters were centralized in Rome, and their origin was estimated to have been after 2007. All individuals within both clusters were males and 37.1% of them had been recently-infected. While C-cluster was entirely composed by Italian men-who-have-sex-with-men, with a median-age of 34 years (IQR:30–39), individuals in CRF17_BF-cluster were older, with a median-age of 51 years (IQR:48–59) and almost all reported sexual-contacts with men and women. All carried R5-tropic viruses, with evidence of atypical or resistance amino-acidic mutations related to NNRTI-drugs (K103Q in C-cluster, and K101E+E138K in CRF17_BF-cluster).Conclusions
These two epidemiological clusters provided evidence of a strong and recent circulation of C and CRF17_BF strains in central Italy, characterized by NNRTI-related mutations among men engaging in high-risk behaviours. These findings underline the role of molecular epidemiology in identifying groups at increased risk of HIV-1 transmission, and in enhancing additional prevention efforts. 相似文献14.
B Sriwanthana M Mori M Tanaka S Nishimura T Miura P Pathipvanich P Sawanpanyalert K Ariyoshi 《PloS one》2012,7(7):e41696
Introduction
The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating.Materials and Methods
14 peptides based on consensus HIV-1 CRF01_AE amino acid sequences were designed for use in IFN-γ ELISpot assays and 51Cr release assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico epitope-HLA prediction was performed.Results
29/66 (43.9%) patients recognized at least one peptide. In total 79 responses were seen against all 14 peptides. 28/79 (35.4%) of the responses were in patients with HLA alleles previously reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in individuals with HLA alleles previously reported to restrict epitopes of HIV clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not associated with HLA alleles previously known to restrict HIV epitopes. In silico epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%) were associated with HLA-C alleles. We further confirmed a novel HLA restriction of a previously identified HIV-1 Gag epitope [p24122–130: PPIPVGDIY (PY9)] by HLA-B*40:01 with a standard 51Cr release assay.Discussion
CTL recognition sites in HIV-1 Gag were similar among different clades but the HLA restriction differed in Thai patients. This disparity in HLA restriction along different populations illustrated the importance of clade- and population-specific HLA analysis prior to CTL vaccine design. 相似文献15.
Grant R. Campbell Erwann P. Loret Stephen A. Spector 《The Journal of biological chemistry》2010,285(3):1681-1691
CXCR4-using human immunodeficiency virus, type 1 (HIV-1) variants emerge late in the course of infection in >40% of individuals infected with clade B HIV-1 but are described less commonly with clade C isolates. Tat is secreted by HIV-1-infected cells where it acts on both uninfected bystander cells and infected cells. In this study, we show that clade B Tat, but not clade C Tat, increases CXCR4 surface expression on resting CD4+ T cells through a CCR2b-dependent mechanism that does not involve de novo protein synthesis. The expression of plectin, a cytolinker protein that plays an important role as a scaffolding platform for proteins involved in cellular signaling including CXCR4 signaling and trafficking, was found to be significantly increased following B Tat but not C Tat treatment. Knockdown of plectin using RNA interference showed that plectin is essential for the B Tat-induced translocation of CXCR4 to the surface of resting CD4+ T cells. The increased surface CXCR4 expression following B Tat treatment led to increased function of CXCR4 including increased chemoattraction toward CXCR4-using-gp120. Moreover, increased CXCR4 surface expression rendered resting CD4+ T cells more permissive to X4 but not R5 HIV-1 infection. However, neither B Tat nor C Tat was able to up-regulate surface expression of CXCR4 on activated CD4+ T cells, and both proteins inhibited the infection of activated CD4+ T cells with X4 but not R5 HIV-1. Thus, B Tat, but not C Tat, has the capacity to render resting, but not activated, CD4+ T cells more susceptible to X4 HIV-1 infection. 相似文献
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HIV-1B亚型gp120基因密码子优化前后免疫原性的比较 总被引:4,自引:0,他引:4
对HIV-1B亚型gp120基因按照哺乳动物优势密码子的使用原则进行优化,以Westem blot方法比较其体外表达量.将优化前的野生型gp120基因和改造后的modgp120基因插入重组腺伴随病毒载体,构建了重组病毒rAAV-wtgp120和rAAV-modgp120,比较两者免疫Balb/C小鼠后的抗体和CTL应答.Western blot检测结果显示:优化后基因的体外表达量明显高于野生型基因,rAAV-modgp120与rAAV-wtgp120相比可更好地诱导Balb/C小鼠的CTL应答,但检测不到明显的抗体反应.由此得出结论,优化后gp120基因的体外表达量明显高于野生型基因,并且可以诱导更强的特异性CTL应答,但检测不到gp120抗体. 相似文献
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Naganawa S Yokoyama M Shiino T Suzuki T Ishigatsubo Y Ueda A Shirai A Takeno M Hayakawa S Sato S Tochikubo O Kiyoura S Sawada K Ikegami T Kanda T Kitamura K Sato H 《PloS one》2008,3(9):e3206
The third variable region (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope gp120 subunit participates in determination of viral infection coreceptor tropism and host humoral immune responses. Positive charge of the V3 plays a key role in determining viral coreceptor tropism. Here, we examined by bioinformatics, experimental, and protein modelling approaches whether the net positive charge of V3 sequence regulates viral sensitivity to humoral immunity. We chose HIV-1 CRF01_AE strain as a model virus to address the question. Diversity analyses using CRF01_AE V3 sequences from 37 countries during 1984 and 2005 (n = 1361) revealed that reduction in the V3's net positive charge makes V3 less variable due to limited positive selection. Consistently, neutralization assay using CRF01_AE V3 recombinant viruses (n = 30) showed that the reduction in the V3's net positive charge rendered HIV-1 less sensitive to neutralization by the blood anti-V3 antibodies. The especially neutralization resistant V3 sequences were the particular subset of the CCR5-tropic V3 sequences with net positive charges of +2 to +4. Molecular dynamics simulation of the gp120 monomers showed that the V3's net positive charge regulates the V3 configuration. This and reported gp120 structural data predict a less-exposed V3 with a reduced net positive charge in the native gp120 trimer context. Taken together, these data suggest a key role of the V3's net positive charge in the immunological escape and coreceptor tropism evolution of HIV-1 CRF01_AE in vivo. The findings have molecular implications for the adaptive evolution and vaccine design of HIV-1. 相似文献
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ChuanYi Ning XingGuang Li WeiMing Tang Bo Zhou WeiPing Cai Joseph D. Tucker 《中国科学:生命科学英文版》2015,58(7):724-726
<正>Dear Editors,Here,we report a novel HIV-1 intra-circulating recombinant form 01_AE(intra-CRF01_AE:CRF01-1AE/CRF01-6AE)composed of CRF01_AE transmission clusters 1 and 6,which was identified in a heterosexual male from Fujian,with one breakpoint observed in the vif gene.The CRF01_AE region I(HXB2:868–5184)of the recombinant clustered with CRF01_AE transmission cluster 1,which is 相似文献