The human immunodeficiency virus （HIV） lentiviral vector is an ideal vector for gene therapy. In the present study, the wild-type HIV-1 genome was segregated into four plasmids, and an optimized novel HIV-1 lentivir...The human immunodeficiency virus （HIV） lentiviral vector is an ideal vector for gene therapy. In the present study, the wild-type HIV-1 genome was segregated into four plasmids, and an optimized novel HIV-1 lentiviral vector containing green fluorescent protein and vesicular stomatitis virus G pseudo-capsule was constructed. The plasmids were pHR-CMV-EGFP, pCMVΔ8.9, pRSV-Rev, pCMV-VSV-G. The four plasmid system was co-transfected into 293T cells, and green fluorescent protein expression was observed. The present study obtained lentiviral particles by high-speed centrifugation, and the lentiviral particle titer was 4 × 108 TU/mL after centrifugation. Thus, an optimized novel HIV-1 lentiviral vector was successfully constructed.展开更多
The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) ...The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) could recognize conformational epitopes that overlap the CD4 bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182 L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182 V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182 L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4 bs epitopes.展开更多
Due to significant advances in the treatment of human immunodeficiency virus type-1(HIV-1), HIV-1 infection gradually has become a treatable chronic disease. Successfully treated HIV-positive individuals can have a no...Due to significant advances in the treatment of human immunodeficiency virus type-1(HIV-1), HIV-1 infection gradually has become a treatable chronic disease. Successfully treated HIV-positive individuals can have a normal life expectancy. Hence, more and more HIV-1 discordant couples in Taiwan and the rest of the world are seeking fertility assistance. Pre-treatment of highly active antiretroviral therapy(HAART) combined with sperm washing and RT-polymerase chain reaction examination for HIV-1 viral load has become the standard procedure to assist them to conceive. However,in order to reduce the transmission risk to the lowest level for the couple and to diminish the cost of health care for the insurance institutes or government, in vitro fertilization(IVF)-intracytoplasmic sperm injection(ICSI) therapy provides the ideal solution for HIV-1 discordant couples with infected men. Intrauterine insemination(IUI) theoretically introduces more than 107 times of sperm counts or semen volume to uninfected women vs IVF-ICSI. However, since some regimens of HAART may significantly decrease the sperm motility, compared to IVF-ICSI, IUI only produces 1/5 to 1/2 pregnancy rates per cycle. Given the risk of seroconversion of HIV infection which actually happens after successful treatment, IVF-ICSI for these HIV-1 seropositive men is more cost-effective and should be the first line treatment for these cases.展开更多
AIM:To corroborate the capacity of Phyto V7,a complex of phytochemicals,to improve the physical well-being of human immunodeficiency virus-1(HIV-1) infected and acquired immune deficiency syndrome(AIDS) patients not u...AIM:To corroborate the capacity of Phyto V7,a complex of phytochemicals,to improve the physical well-being of human immunodeficiency virus-1(HIV-1) infected and acquired immune deficiency syndrome(AIDS) patients not undergoing antiretroviral treatment.METHODS:Two hundred and thirty nine HIV-1 seropositive male and female voluntary inmates were recruited through the Uruguay National Program of AIDS.The study participants received for 90 consecutive days every eight hours two tablets(760 mg/each) of Phyto V7,containing a mix of the following phytochemicals:flavonols(Kaempferol,Quercetin),flavones(Apigenin,Luteolin),hydroxycinnamic acids(ferrulic acid),carotenoids(Lutein,Lycopene,Beta carotene) and organosulfur compounds,all from vegetal origin.The participants did not receive any antiretroviral treatment during the study.At days 0,30,60 and 90(± 2 d) the participants were evaluated for body mass index(BMI),tolerance to Phyto V7 and Index of Quality of Life based on the Karfnosky scale.ANOVA,Tukey Post-test,χ2 test and Wilcoxon Signed Rank test were used to analyze the effect of treatment.RESULTS:One hundred and nighty nine study participants finished the study.Already after 30 d of Phyto V7 consumption,the weight,BMI and Karnofsky score statistically significantly improved(P < 0.001),and continued to improve until the end of the study.The mean weight gain per participant during the 90 d wasof 1.21 kg(approximately 2% of body weight).The overall increase in the mean Karnofsky score after 90 d was 14.08%.The lower the BMI and Karnofsky score of the participants were at the beginning of the study,the more notorious was the improvement over time.For example,the mean increment of Index of Quality of Life,among the participants with an initial Karnofsky score of 5 or below(n = 33) from day 0 to day 90,was of 35.67%(0.476 ± 0.044 vs 0.645 ± 0.09; P < 0.001).The tolerability to Phyto V7 was very good and no adverse reactions were recorded or reported.CONCLUSION:Administration of the Phyto V7 can be an important tool to improve the well-being of HIV-1 seropositive individuals and AIDS patients,not undergoing antiretroviral treatment.展开更多
Human immunodeficiency virus type 1(HIV-1) persistence is a major barrier to the successful treatment and eradication of acquired immunodeficiency syndrome(AIDS).In addition to resting CD4+ T cells,a significant long-...Human immunodeficiency virus type 1(HIV-1) persistence is a major barrier to the successful treatment and eradication of acquired immunodeficiency syndrome(AIDS).In addition to resting CD4+ T cells,a significant long-lived compartment of HIV-1 infection in vivo includes blood monocytes and tissue macrophages.Studying HIV-1 persistence in monocyte-lineage cells is critical because these cells are important HIV-1 target cells in vivo.Monocyte-lineage cells,including monocytes,dendritic cells(DCs) and macrophages,play a significant role in HIV-1 infection and transmission.These cells have been implicated as viral reservoirs that facilitate HIV-1 latency and persistence.A better understanding of HIV-1 interactions with monocyte-lineage cells can potentially aid in the development of new approaches for intervention.This minireview highlights the latest advances in understanding the role of monocyte-lineage cells in HIV-1 persistence and emphasizes new insights into the mechanisms underlying viral persistence.展开更多
While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from th...While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference(RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by noncoding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing(TGS), as well as finetuning their expression through post-transcriptional gene silencing(PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells.展开更多
Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progre...Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progressive weakness, stiffness, and a lower limb spastic paraparesis. In some cases, polymyositis, inclusion bodymyositis, or amyotrophic lateral sclerosis-like syndromes are associated with HTLV-1. TSP was first described in Jamaica in 1888 and known as Jamaican peripheral neuritis before TSP was related to HTLV-1 virus, the first retrovirus being identified, and the disease is since named HAM/TSP. There is no established treatment program for HAM/TSP. Prevention is difficult in lowincome patients(i.e., HTLV-1 infected breast feeding mothers in rural areas, sex workers). Thus, there is a need for new therapeutic avenues. Therapeutic approaches must be based on a better understanding, not only of clinical and clinicopathological data, but also of the pathophysiology of the affection. Consequently, a better understanding of existing or newly developed animal models of HAM/TSP is a prerequisite step in the development of new treatments.展开更多
Human T lymphotropic virus type 1 (HTLV-1) is endemic in the southern part of Japan. Infection of the virus can cause adult T cell leukemia/lymphoma (ATL), while most infected individuals remain in a carrier state for...Human T lymphotropic virus type 1 (HTLV-1) is endemic in the southern part of Japan. Infection of the virus can cause adult T cell leukemia/lymphoma (ATL), while most infected individuals remain in a carrier state for a long period of time. Although rare cases of carriers, like ATL patients, who developed opportunistic infections, have been reported, hematological changes of carriers who are prone to opportunistic infections have not been well defined. Here, we present a case of an HTLV-1 carrier who developed Mycobacterium intracellulare infection and Pneumocystis jirovecii pneumonia (PcP) simultaneously. Flow cytometric analysis of bone marrow cells revealed an aberrant compositional change similar to that in ATL patients. This suggests the presence of a pre-ATL state prior to the development of ATL, which is notable in terms of underlying cellular immunodeficiency.展开更多
The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the a...The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen(HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper(Tfh) cells, germinal centers,and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death(PD)-1^+T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center(GC)reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1^+T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.展开更多
There are two types of Human Immunodeficiency Virus （HIV）： HIV-1 and HIV-2. HIV-1 dominates epidemics in many different parts of the world, and HIV-2 is principally responsible for the epidemic in westem Africa. In...There are two types of Human Immunodeficiency Virus （HIV）： HIV-1 and HIV-2. HIV-1 dominates epidemics in many different parts of the world, and HIV-2 is principally responsible for the epidemic in westem Africa. In China, Zeng et al have reported the first individual infected with HIV-1 in 1985. And in the 1990s, there was a severe epidemic involving the HIV-1 B＇ strain among people who sold blood and plasma in Henan, Hubei and adjacent provinces. To further study in HIV/AIDS vaccines and HIV-1 drug resistance for people in these regions, we need to construct an infectious HIV-1 B＇ molecular clone which is representative of the virus in these areas. To this end, we have isolated a HIV-1 B＇ virus from a child who was infected with HIV-1 from his mother in Hubei province, and have constructed a full-length clone from this genome.展开更多
A new set of descriptors,namely score vectors of the zero dimension,one dimension,two dimensions and three dimensions(SZOTT),was derived from principle component analysis of a matrix of 1369 structural variables inclu...A new set of descriptors,namely score vectors of the zero dimension,one dimension,two dimensions and three dimensions(SZOTT),was derived from principle component analysis of a matrix of 1369 structural variables including 0D,1D,2D and 3D information for the 20 coded amino acids. SZOTT scales were then used in cleavage site prediction of human immunodeficiency virus type 1 protease. Linear discriminant analysis(LDA) and support vector machines(SVM) were applied to developing models to predict the cleavage sites. The results obtained by linear discriminant analysis(LDA) and support vector machines(SVM) are as follows. The Matthews correlation coefficients(MCC) by the resubstitution test,leave-one-out cross validation(LOOCV) and external validation are 0.879 and 0.911,0.849 and 0.901,0.822 and 0.846,respectively. The receiver operating characteristic(ROC) analysis showed that the SVM model possesses better simulative and predictive ability in comparison with the LDA model. Satisfactory results show that SZOTT descriptors can be further used to predict cleavage sites of human immunodeficiency virus type 1 protease.展开更多
Despite the success of antiretroviral therapy(ART),efforts to develop new classes of antiviral agents have been hampered by the emergence of drug resistance.Dibenzo-indole-bearing aristolactams are compounds that have...Despite the success of antiretroviral therapy(ART),efforts to develop new classes of antiviral agents have been hampered by the emergence of drug resistance.Dibenzo-indole-bearing aristolactams are compounds that have been isolated from various plants species and which show several clinically relevant effects,including anti-inflammatory,antiplatelet,and antimycobacterial actions.However,the effect of these compounds on human immunodeficiency virus type 1(HIV-1)infection has not yet been studied.In this study,we discovered an aristolactam derivative bearing dibenzo[cd,f]indol-4(5 H)-one that had a potent anti-HIV-1 effect.A structure-activity relationship(SAR)study using nine synthetic derivatives of aristolactam identified the differing effects of residue substitutions on the inhibition of HIV-1 infection and cell viability.Among the compounds tested,1,2,8,9-tetramethoxy-5-(2-(piperidin-1-yl)ethyl)-dibenzo[cd,f]indol-4(5 H)-one(Compound 2)exhibited the most potent activity by inhibiting HIV-1 infection with a half-maximal inhibitory concentration(IC50)of 1.03 lmol/L and a half-maximal cytotoxic concentration(CC50)of 16.91 lmol/L(selectivity index,16.45).The inhibitory effect of the compounds on HIV-1 infection was linked to inhibition of the viral replication cycle.Mode-of-action studies showed that the aristolactam derivatives did not affect reverse transcription or integration;instead,they specifically inhibited Tat-mediated viral transcription.Taken together,these findings show that several aristolactam derivatives impaired HIV-1 infection by inhibiting the activity of Tat-mediated viral transcription,and suggest that these derivatives could be antiviral drug candidates.展开更多
基金the National Natural Science Foundation of China, No. 30770755
文摘The human immunodeficiency virus （HIV） lentiviral vector is an ideal vector for gene therapy. In the present study, the wild-type HIV-1 genome was segregated into four plasmids, and an optimized novel HIV-1 lentiviral vector containing green fluorescent protein and vesicular stomatitis virus G pseudo-capsule was constructed. The plasmids were pHR-CMV-EGFP, pCMVΔ8.9, pRSV-Rev, pCMV-VSV-G. The four plasmid system was co-transfected into 293T cells, and green fluorescent protein expression was observed. The present study obtained lentiviral particles by high-speed centrifugation, and the lentiviral particle titer was 4 × 108 TU/mL after centrifugation. Thus, an optimized novel HIV-1 lentiviral vector was successfully constructed.
基金supported by grants from National Science and Technology Major Project(2012ZX10004701)
文摘The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) could recognize conformational epitopes that overlap the CD4 bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182 L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182 V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182 L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4 bs epitopes.
文摘Due to significant advances in the treatment of human immunodeficiency virus type-1(HIV-1), HIV-1 infection gradually has become a treatable chronic disease. Successfully treated HIV-positive individuals can have a normal life expectancy. Hence, more and more HIV-1 discordant couples in Taiwan and the rest of the world are seeking fertility assistance. Pre-treatment of highly active antiretroviral therapy(HAART) combined with sperm washing and RT-polymerase chain reaction examination for HIV-1 viral load has become the standard procedure to assist them to conceive. However,in order to reduce the transmission risk to the lowest level for the couple and to diminish the cost of health care for the insurance institutes or government, in vitro fertilization(IVF)-intracytoplasmic sperm injection(ICSI) therapy provides the ideal solution for HIV-1 discordant couples with infected men. Intrauterine insemination(IUI) theoretically introduces more than 107 times of sperm counts or semen volume to uninfected women vs IVF-ICSI. However, since some regimens of HAART may significantly decrease the sperm motility, compared to IVF-ICSI, IUI only produces 1/5 to 1/2 pregnancy rates per cycle. Given the risk of seroconversion of HIV infection which actually happens after successful treatment, IVF-ICSI for these HIV-1 seropositive men is more cost-effective and should be the first line treatment for these cases.
文摘AIM:To corroborate the capacity of Phyto V7,a complex of phytochemicals,to improve the physical well-being of human immunodeficiency virus-1(HIV-1) infected and acquired immune deficiency syndrome(AIDS) patients not undergoing antiretroviral treatment.METHODS:Two hundred and thirty nine HIV-1 seropositive male and female voluntary inmates were recruited through the Uruguay National Program of AIDS.The study participants received for 90 consecutive days every eight hours two tablets(760 mg/each) of Phyto V7,containing a mix of the following phytochemicals:flavonols(Kaempferol,Quercetin),flavones(Apigenin,Luteolin),hydroxycinnamic acids(ferrulic acid),carotenoids(Lutein,Lycopene,Beta carotene) and organosulfur compounds,all from vegetal origin.The participants did not receive any antiretroviral treatment during the study.At days 0,30,60 and 90(± 2 d) the participants were evaluated for body mass index(BMI),tolerance to Phyto V7 and Index of Quality of Life based on the Karfnosky scale.ANOVA,Tukey Post-test,χ2 test and Wilcoxon Signed Rank test were used to analyze the effect of treatment.RESULTS:One hundred and nighty nine study participants finished the study.Already after 30 d of Phyto V7 consumption,the weight,BMI and Karnofsky score statistically significantly improved(P < 0.001),and continued to improve until the end of the study.The mean weight gain per participant during the 90 d wasof 1.21 kg(approximately 2% of body weight).The overall increase in the mean Karnofsky score after 90 d was 14.08%.The lower the BMI and Karnofsky score of the participants were at the beginning of the study,the more notorious was the improvement over time.For example,the mean increment of Index of Quality of Life,among the participants with an initial Karnofsky score of 5 or below(n = 33) from day 0 to day 90,was of 35.67%(0.476 ± 0.044 vs 0.645 ± 0.09; P < 0.001).The tolerability to Phyto V7 was very good and no adverse reactions were recorded or reported.CONCLUSION:Administration of the Phyto V7 can be an important tool to improve the well-being of HIV-1 seropositive individuals and AIDS patients,not undergoing antiretroviral treatment.
基金supported in part by grants(AI068493 and AI078762)from the National Institutes of Health,USA
文摘Human immunodeficiency virus type 1(HIV-1) persistence is a major barrier to the successful treatment and eradication of acquired immunodeficiency syndrome(AIDS).In addition to resting CD4+ T cells,a significant long-lived compartment of HIV-1 infection in vivo includes blood monocytes and tissue macrophages.Studying HIV-1 persistence in monocyte-lineage cells is critical because these cells are important HIV-1 target cells in vivo.Monocyte-lineage cells,including monocytes,dendritic cells(DCs) and macrophages,play a significant role in HIV-1 infection and transmission.These cells have been implicated as viral reservoirs that facilitate HIV-1 latency and persistence.A better understanding of HIV-1 interactions with monocyte-lineage cells can potentially aid in the development of new approaches for intervention.This minireview highlights the latest advances in understanding the role of monocyte-lineage cells in HIV-1 persistence and emphasizes new insights into the mechanisms underlying viral persistence.
文摘While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference(RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by noncoding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing(TGS), as well as finetuning their expression through post-transcriptional gene silencing(PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells.
文摘Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progressive weakness, stiffness, and a lower limb spastic paraparesis. In some cases, polymyositis, inclusion bodymyositis, or amyotrophic lateral sclerosis-like syndromes are associated with HTLV-1. TSP was first described in Jamaica in 1888 and known as Jamaican peripheral neuritis before TSP was related to HTLV-1 virus, the first retrovirus being identified, and the disease is since named HAM/TSP. There is no established treatment program for HAM/TSP. Prevention is difficult in lowincome patients(i.e., HTLV-1 infected breast feeding mothers in rural areas, sex workers). Thus, there is a need for new therapeutic avenues. Therapeutic approaches must be based on a better understanding, not only of clinical and clinicopathological data, but also of the pathophysiology of the affection. Consequently, a better understanding of existing or newly developed animal models of HAM/TSP is a prerequisite step in the development of new treatments.
文摘Human T lymphotropic virus type 1 (HTLV-1) is endemic in the southern part of Japan. Infection of the virus can cause adult T cell leukemia/lymphoma (ATL), while most infected individuals remain in a carrier state for a long period of time. Although rare cases of carriers, like ATL patients, who developed opportunistic infections, have been reported, hematological changes of carriers who are prone to opportunistic infections have not been well defined. Here, we present a case of an HTLV-1 carrier who developed Mycobacterium intracellulare infection and Pneumocystis jirovecii pneumonia (PcP) simultaneously. Flow cytometric analysis of bone marrow cells revealed an aberrant compositional change similar to that in ATL patients. This suggests the presence of a pre-ATL state prior to the development of ATL, which is notable in terms of underlying cellular immunodeficiency.
基金supported by the Grant of National Natural Science Foundation of China (Grant number 81271824, 81772190, 81601755)the Grant of National Science and Technology Major Project (Grant number 2012ZX10001009-002003)
文摘The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen(HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper(Tfh) cells, germinal centers,and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death(PD)-1^+T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center(GC)reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1^+T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.
基金This study was supported by the grants from the National High Technology Program 863(2005AA219070)the Project 973 of the National Program of China(2005CB522903).
文摘There are two types of Human Immunodeficiency Virus （HIV）： HIV-1 and HIV-2. HIV-1 dominates epidemics in many different parts of the world, and HIV-2 is principally responsible for the epidemic in westem Africa. In China, Zeng et al have reported the first individual infected with HIV-1 in 1985. And in the 1990s, there was a severe epidemic involving the HIV-1 B＇ strain among people who sold blood and plasma in Henan, Hubei and adjacent provinces. To further study in HIV/AIDS vaccines and HIV-1 drug resistance for people in these regions, we need to construct an infectious HIV-1 B＇ molecular clone which is representative of the virus in these areas. To this end, we have isolated a HIV-1 B＇ virus from a child who was infected with HIV-1 from his mother in Hubei province, and have constructed a full-length clone from this genome.
基金Supported by the Research on National High-tech R&D Program (the 863 program) (Grant No. 2006AA02Z312)Innovative Group Program for Graduates of Chong- qing University, Science and Innovation Fund (Grant No. 200711C1A0010260)
文摘A new set of descriptors,namely score vectors of the zero dimension,one dimension,two dimensions and three dimensions(SZOTT),was derived from principle component analysis of a matrix of 1369 structural variables including 0D,1D,2D and 3D information for the 20 coded amino acids. SZOTT scales were then used in cleavage site prediction of human immunodeficiency virus type 1 protease. Linear discriminant analysis(LDA) and support vector machines(SVM) were applied to developing models to predict the cleavage sites. The results obtained by linear discriminant analysis(LDA) and support vector machines(SVM) are as follows. The Matthews correlation coefficients(MCC) by the resubstitution test,leave-one-out cross validation(LOOCV) and external validation are 0.879 and 0.911,0.849 and 0.901,0.822 and 0.846,respectively. The receiver operating characteristic(ROC) analysis showed that the SVM model possesses better simulative and predictive ability in comparison with the LDA model. Satisfactory results show that SZOTT descriptors can be further used to predict cleavage sites of human immunodeficiency virus type 1 protease.
基金supported by grants from the Korea National Institute of Health (Grant Number:2019-NI-066-00 and 2020-ER5106-00)。
文摘Despite the success of antiretroviral therapy(ART),efforts to develop new classes of antiviral agents have been hampered by the emergence of drug resistance.Dibenzo-indole-bearing aristolactams are compounds that have been isolated from various plants species and which show several clinically relevant effects,including anti-inflammatory,antiplatelet,and antimycobacterial actions.However,the effect of these compounds on human immunodeficiency virus type 1(HIV-1)infection has not yet been studied.In this study,we discovered an aristolactam derivative bearing dibenzo[cd,f]indol-4(5 H)-one that had a potent anti-HIV-1 effect.A structure-activity relationship(SAR)study using nine synthetic derivatives of aristolactam identified the differing effects of residue substitutions on the inhibition of HIV-1 infection and cell viability.Among the compounds tested,1,2,8,9-tetramethoxy-5-(2-(piperidin-1-yl)ethyl)-dibenzo[cd,f]indol-4(5 H)-one(Compound 2)exhibited the most potent activity by inhibiting HIV-1 infection with a half-maximal inhibitory concentration(IC50)of 1.03 lmol/L and a half-maximal cytotoxic concentration(CC50)of 16.91 lmol/L(selectivity index,16.45).The inhibitory effect of the compounds on HIV-1 infection was linked to inhibition of the viral replication cycle.Mode-of-action studies showed that the aristolactam derivatives did not affect reverse transcription or integration;instead,they specifically inhibited Tat-mediated viral transcription.Taken together,these findings show that several aristolactam derivatives impaired HIV-1 infection by inhibiting the activity of Tat-mediated viral transcription,and suggest that these derivatives could be antiviral drug candidates.
