The aim of this study was to investigate the interaction between polymers polyApolyU (RNA) and two general anti-viral drugs with anti-HIV-1 activities. Tm experiment showed that the compounds had interacted with RNA, ...The aim of this study was to investigate the interaction between polymers polyApolyU (RNA) and two general anti-viral drugs with anti-HIV-1 activities. Tm experiment showed that the compounds had interacted with RNA, and CD spectra also observed the changes of RNA conformation induced by the compounds. Cytometric flow analysis indicated that ribavirin and DII-18-2 could decrease the percentage of hypodiploid cells, especially ribavirin.展开更多
Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV...Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses. No difference in the neutralizing activities between the plasma from LTNP and TP was found, which was consistent with the most recent reports. In addition, no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found. The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.展开更多
Objective- To compare the consistency of the results from detecting HIV-1 antibody in the paired urine and serum specimens from drug users by ELISA. Methods: The paired urine and serum specimens from 273 drug users de...Objective- To compare the consistency of the results from detecting HIV-1 antibody in the paired urine and serum specimens from drug users by ELISA. Methods: The paired urine and serum specimens from 273 drug users detained at a detoxification unit were collected, and the HIV-1 antibodies in the specimens of them were screened by urine and serum ELISA kits, respectively. Results: Of 273 serum specimens, 94 ones showed positive reaction and among 94 counterpart urine specimens, 93 ones also appeared positive reaction. Taking the results together,the consistent rate of HIV-1 antibody screened by urine and serum ELISA kits was 99.6%. Conclusion: The urine ELISA kit, which screened HIV-1 antibody of urine showing almost the same results tested by serum ELISA kit, is reliable. It is proposed that urine ELISA be introduced in many fields.展开更多
Objective: To analyze the genotypes of CCR5 △ 32,CCR2b-64I and SDF 1-3 A and mutation frequencies of allelicgenes in Chinese populations infected with HIV-1. Methods: Genome DNA from peripheral blood mononuclearcells...Objective: To analyze the genotypes of CCR5 △ 32,CCR2b-64I and SDF 1-3 A and mutation frequencies of allelicgenes in Chinese populations infected with HIV-1. Methods: Genome DNA from peripheral blood mononuclearcells (PBMCs) of 78 HIV-1 infectors was amplified bypolymerase chain reaction (PCR). CCR5, CCR2b and SDF1gene fragments were obtained from restrictive fragmentlength polymorphism (RFLP) and/or CCR△32, CCR5m303,CCR2b-64I and SDF1-3' A allelic genes' mutationalfrequencies were sequenced directly from PCR products. Results: None of CCR5△32, CCR5m303 gene mutationwere found in 78 subjects with HIV-1 infection. The allelicgene mutation frequencies of CCR2b-64I and SDF1-3'Acorresponding to 14.9-34.0% and 17.6-38.2% of 95% CI, were22.79% and 26.92% respectively. Their colony distributionconformed to the Hardy-Weinberg equilibrium. Conclusion: The HIV-1 infections found at present are allsusceptible population of CCR5△32 and CCR5m303. Thepolymorphism and frequencies of CCR5△32, CCR5m303,CCR2b-64I and SDF1-3'A alleles from Chinese HIV-1infected population were disclosed in this study for the firsttime, which is of significance for studying the geneticresistance to susceptibility to HIV-1 infection as well as AIDSdisease progression.展开更多
More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last dec...More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.展开更多
The cellular protein tetherin tethers the HIV-1 viral particles on the cellular membrane to inhibit the replication of HIV-1. However, the HIV-1 accessory protein Vpu counteracts the antiviral function of tetherin. In...The cellular protein tetherin tethers the HIV-1 viral particles on the cellular membrane to inhibit the replication of HIV-1. However, the HIV-1 accessory protein Vpu counteracts the antiviral function of tetherin. In this study, two retroviral vector plasmids were constructed. One inhibited the vpu gene expression; the other one over-expressed the tetherin. Both retroviral vector plasmids could be packaged in the packaging cell line PT67 to obtain the corresponding retroviruses. The retroviral vector plasmids＇ functions of tetherin over-expression or vpu-RNAi were detected at the cell level. Retroviral vector plasmids were transfected to PT67 cells at different ratios from 0T3V to 3TOV, and then mixed retroviruses were harvested. The antiviral functions of mixed retroviruses were detected in HIV-1 infected TZM-bi cells. The results showed that packaged mixed retroviruses could repress the replication of HIV-1 in TZM-bl cells.展开更多
Recent studies have demonstrated that the membrane-proximal external region （MPER） of human immunodeficiency virus 1 （HIV-1） glycoprotein 41 contains a series of epitopes for human monoclonal antibodies, including...Recent studies have demonstrated that the membrane-proximal external region （MPER） of human immunodeficiency virus 1 （HIV-1） glycoprotein 41 contains a series of epitopes for human monoclonal antibodies, including 2F5, Zl3el, 4El0, and 10E8, which were isolated from HIV-l-infected individuals and show broad neutralizing activities. This suggests that MPER is a good target for the development of effective HIV-1 vaccines. However, many studies have shown that it is difficult to induce antibodies with similar broad neutralizing activities using MPER-based peptide antigens. Here, we report that 10E8-1ike neu- tralizing antibodies with effective anti-HIV-1 activity were readily induced using a precisely designed conformational immu- nogenic peptide containing the 10E8-specific epitope. This immunogenic peptide （designated T10HE） contains a 15-mer MPER-derived 10E8-specific epitope fused to T-helper-cell epitopes from tetanus toxin （tt）, which showed a significantly sta- bilized a-helix structure after a series of modifications, including substitution with an （S）-c^-（2＇-pentenyl） alanine containing an olefin-bearing tether and ruthenium-catalyzed olefin metathesis, compared with the unmodified T10E peptide. The stabilized （x-helix structure of T10HE did not affect its capacity to bind the 10E8 antibody, as evaluated with an enzyme linked immuno- sorbent assay （ELISA） and surface plasmon resonance binding assay （SPR assay）. The efficacies of the T10HE and T10E epitope vaccines were evaluated after a standard vaccination procedure in which the experimental mice were primed with ei- ther the T10HE or T10E immunogen and boosted with HIV-1 JRFL pseudoviruses. Higher titers of 10E8-1ike antibodies were induced by T10HE than that by T10E. More importantly, the antibodies induced by T10HE showed enhanced antiviral potency against HIV-1 strains with both X4 and R5 tropism and a greater degree of broad neutralizing activity than the antibodies in- duced by T10E. These results indicate that a 10E8-epitope-based structure-specific peptide immunogen can elicit neutralizing antibodies when used as a vaccine prime.展开更多
In this paper, we revisit the model by Guedj et al. [J. Guedj, R. Thibaut and D. Commenges, Maximum likelihood estimation in dynamical models of HIV, Biometrics 63 （2007） 198-206; J. Guedj, R. Thibaut and D. Commeng...In this paper, we revisit the model by Guedj et al. [J. Guedj, R. Thibaut and D. Commenges, Maximum likelihood estimation in dynamical models of HIV, Biometrics 63 （2007） 198-206; J. Guedj, R. Thibaut and D. Commenges, Practical identifiability of HIV dynamics models, Bull. Math. Biol. 69 （2007） 2493 2513] which describes the effect of treatment with reverse transcriptase （RT） inhibitors and incorporates the class of quiescent cells. We prove that there is a threshold value 7 of drug efficiency η such that if η 〉 7, the basic reproduction number R0 〈 1 and the infection is cleared and if η〈 η^-, the infectious equilibrium is globally asymptotically stable. When the drug efficiency function η（t） is periodic and of the bang-bang type we establish a threshold, in terms of spectral radius of some matrix, between the clearance and the persistence of the disease. As stated in related works [L. Rong, Z. Feng and A. Perelson, Emergence of HIV-1 drug resistance during antiretroviral treatment, Bull. Math. Biol. 69 （2007） 2027-2060; P. De Leenheer, Within-host virus models with periodic antiviral therapy, Bull. Math. Biol. 71 （2009） 189-210.], we prove that the increase of the drug efficiency or the active duration of drug must clear the infection more quickly. We illustrate our results by some numerical simulations.展开更多
基金This project was supported by the National Natural Science Foundation of China Doctoral Program Foundation of China.
文摘The aim of this study was to investigate the interaction between polymers polyApolyU (RNA) and two general anti-viral drugs with anti-HIV-1 activities. Tm experiment showed that the compounds had interacted with RNA, and CD spectra also observed the changes of RNA conformation induced by the compounds. Cytometric flow analysis indicated that ribavirin and DII-18-2 could decrease the percentage of hypodiploid cells, especially ribavirin.
基金supported in part by the National Key S&T Special Projects on Major Infectious Diseases (Grant No. 2008ZX10001-002, 2008ZX10001-012)the National Natural Science Foundation of China (No. 30700706)
文摘Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses. No difference in the neutralizing activities between the plasma from LTNP and TP was found, which was consistent with the most recent reports. In addition, no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found. The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.
文摘Objective- To compare the consistency of the results from detecting HIV-1 antibody in the paired urine and serum specimens from drug users by ELISA. Methods: The paired urine and serum specimens from 273 drug users detained at a detoxification unit were collected, and the HIV-1 antibodies in the specimens of them were screened by urine and serum ELISA kits, respectively. Results: Of 273 serum specimens, 94 ones showed positive reaction and among 94 counterpart urine specimens, 93 ones also appeared positive reaction. Taking the results together,the consistent rate of HIV-1 antibody screened by urine and serum ELISA kits was 99.6%. Conclusion: The urine ELISA kit, which screened HIV-1 antibody of urine showing almost the same results tested by serum ELISA kit, is reliable. It is proposed that urine ELISA be introduced in many fields.
文摘Objective: To analyze the genotypes of CCR5 △ 32,CCR2b-64I and SDF 1-3 A and mutation frequencies of allelicgenes in Chinese populations infected with HIV-1. Methods: Genome DNA from peripheral blood mononuclearcells (PBMCs) of 78 HIV-1 infectors was amplified bypolymerase chain reaction (PCR). CCR5, CCR2b and SDF1gene fragments were obtained from restrictive fragmentlength polymorphism (RFLP) and/or CCR△32, CCR5m303,CCR2b-64I and SDF1-3' A allelic genes' mutationalfrequencies were sequenced directly from PCR products. Results: None of CCR5△32, CCR5m303 gene mutationwere found in 78 subjects with HIV-1 infection. The allelicgene mutation frequencies of CCR2b-64I and SDF1-3'Acorresponding to 14.9-34.0% and 17.6-38.2% of 95% CI, were22.79% and 26.92% respectively. Their colony distributionconformed to the Hardy-Weinberg equilibrium. Conclusion: The HIV-1 infections found at present are allsusceptible population of CCR5△32 and CCR5m303. Thepolymorphism and frequencies of CCR5△32, CCR5m303,CCR2b-64I and SDF1-3'A alleles from Chinese HIV-1infected population were disclosed in this study for the firsttime, which is of significance for studying the geneticresistance to susceptibility to HIV-1 infection as well as AIDSdisease progression.
基金This project has been funded in whole or in part with federal funds from the National Cancer Institute,National Institutes of Health, under contract N01-CO-12400
文摘More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.
基金National Natural Science Foundation of China(81101245,30970162)The Fundamental Research Funds for the Central Universities(65011871)National Training Programs of Innovation for Undergraduates(111005505)
文摘The cellular protein tetherin tethers the HIV-1 viral particles on the cellular membrane to inhibit the replication of HIV-1. However, the HIV-1 accessory protein Vpu counteracts the antiviral function of tetherin. In this study, two retroviral vector plasmids were constructed. One inhibited the vpu gene expression; the other one over-expressed the tetherin. Both retroviral vector plasmids could be packaged in the packaging cell line PT67 to obtain the corresponding retroviruses. The retroviral vector plasmids＇ functions of tetherin over-expression or vpu-RNAi were detected at the cell level. Retroviral vector plasmids were transfected to PT67 cells at different ratios from 0T3V to 3TOV, and then mixed retroviruses were harvested. The antiviral functions of mixed retroviruses were detected in HIV-1 infected TZM-bi cells. The results showed that packaged mixed retroviruses could repress the replication of HIV-1 in TZM-bl cells.
基金supported by Ministry of Science and Technology of China(2012ZX10001-009)
文摘Recent studies have demonstrated that the membrane-proximal external region （MPER） of human immunodeficiency virus 1 （HIV-1） glycoprotein 41 contains a series of epitopes for human monoclonal antibodies, including 2F5, Zl3el, 4El0, and 10E8, which were isolated from HIV-l-infected individuals and show broad neutralizing activities. This suggests that MPER is a good target for the development of effective HIV-1 vaccines. However, many studies have shown that it is difficult to induce antibodies with similar broad neutralizing activities using MPER-based peptide antigens. Here, we report that 10E8-1ike neu- tralizing antibodies with effective anti-HIV-1 activity were readily induced using a precisely designed conformational immu- nogenic peptide containing the 10E8-specific epitope. This immunogenic peptide （designated T10HE） contains a 15-mer MPER-derived 10E8-specific epitope fused to T-helper-cell epitopes from tetanus toxin （tt）, which showed a significantly sta- bilized a-helix structure after a series of modifications, including substitution with an （S）-c^-（2＇-pentenyl） alanine containing an olefin-bearing tether and ruthenium-catalyzed olefin metathesis, compared with the unmodified T10E peptide. The stabilized （x-helix structure of T10HE did not affect its capacity to bind the 10E8 antibody, as evaluated with an enzyme linked immuno- sorbent assay （ELISA） and surface plasmon resonance binding assay （SPR assay）. The efficacies of the T10HE and T10E epitope vaccines were evaluated after a standard vaccination procedure in which the experimental mice were primed with ei- ther the T10HE or T10E immunogen and boosted with HIV-1 JRFL pseudoviruses. Higher titers of 10E8-1ike antibodies were induced by T10HE than that by T10E. More importantly, the antibodies induced by T10HE showed enhanced antiviral potency against HIV-1 strains with both X4 and R5 tropism and a greater degree of broad neutralizing activity than the antibodies in- duced by T10E. These results indicate that a 10E8-epitope-based structure-specific peptide immunogen can elicit neutralizing antibodies when used as a vaccine prime.
文摘In this paper, we revisit the model by Guedj et al. [J. Guedj, R. Thibaut and D. Commenges, Maximum likelihood estimation in dynamical models of HIV, Biometrics 63 （2007） 198-206; J. Guedj, R. Thibaut and D. Commenges, Practical identifiability of HIV dynamics models, Bull. Math. Biol. 69 （2007） 2493 2513] which describes the effect of treatment with reverse transcriptase （RT） inhibitors and incorporates the class of quiescent cells. We prove that there is a threshold value 7 of drug efficiency η such that if η 〉 7, the basic reproduction number R0 〈 1 and the infection is cleared and if η〈 η^-, the infectious equilibrium is globally asymptotically stable. When the drug efficiency function η（t） is periodic and of the bang-bang type we establish a threshold, in terms of spectral radius of some matrix, between the clearance and the persistence of the disease. As stated in related works [L. Rong, Z. Feng and A. Perelson, Emergence of HIV-1 drug resistance during antiretroviral treatment, Bull. Math. Biol. 69 （2007） 2027-2060; P. De Leenheer, Within-host virus models with periodic antiviral therapy, Bull. Math. Biol. 71 （2009） 189-210.], we prove that the increase of the drug efficiency or the active duration of drug must clear the infection more quickly. We illustrate our results by some numerical simulations.
