Dear Editor,Recombination contributes greatly to the diversity of human immunodeficiency virus type 1（HIV-1）.A large number of recombinant strains have been found in China,particularly in Yunnan,which is considered ...Dear Editor,Recombination contributes greatly to the diversity of human immunodeficiency virus type 1（HIV-1）.A large number of recombinant strains have been found in China,particularly in Yunnan,which is considered the HIV-1 epicenter of China.Surveillance of unique recombinant forms is helpful for prediction of new circulating recombinant forms.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
Background Virus with nucleoside reverse transcriptase inhibitors （NRTIs） or nonnucleoside reverse transcriptase inhibitors （NNRTIs） resistant mutations show different evolution tendencies when the anti-viral ther...Background Virus with nucleoside reverse transcriptase inhibitors （NRTIs） or nonnucleoside reverse transcriptase inhibitors （NNRTIs） resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine （3TC） or nevirapine （NVP） resistant mutations. Methods 3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay. Results 3TC-resistant （M184I mutation） and NVP-resistant （Y181I mutation） virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages. Conclusions The NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.展开更多
Background:The casein kinase 2-interacting protein-1(CKIP-1)is important in the development of osteoblasts and cardiomyocytes.However,the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells(MSCs)remain un...Background:The casein kinase 2-interacting protein-1(CKIP-1)is important in the development of osteoblasts and cardiomyocytes.However,the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells(MSCs)remain unclear.This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation.Methods:Bone marrow MSCs of CKIP-1 wild type(WT)and knockout(KO)mice were cultivated in vitro.Cell phenotype was analyzed by flow cytometry,colony formation was detected to study the proliferative ability.Osteogenic and adipogenic induction were performed.The osteogenic ability was explored by alizarin red staining,alkaline phosphatase(ALP)staining and ALP activity detection.Quantitative real-time polymerase chain reaction(qRT-PCR)was carried out to determine the mRNA expression levels of osteoblast marker genes.The adipogenic ability was detected by oil red O staining.Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume(BV/TV),bone surface area fraction/trabecular BV,trabecular number(Tb.N),and trabecular spacing(Tb.sp).Interleukin(IL)-1b was injected on WT mice of 2 months old and 18 months old,respectively.Difference in CKIP-1 expression was detected by RT-PCR and western blot.The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot.Results:ALP assays,alizarin red staining,and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis.Micro-computed tomography detection showed that among 18-month-old mice,CKIP-1 KO mice presented significantly higher bone mass compared withWTmice(P=0.02).No significant difference was observed in 2-month-old mice.In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice(4.3-fold increase at themRNA level,P=0.04).Finally,the expression levels of CKIP-1 in bone marrow(3.2-fold increase at themRNA level,P=0.03)and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1b.Conclusions:CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects.Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.展开更多
Background:HIV-1 Vpu acts by counteracting the tethering function of tetherin and resulting in the release of HIV-1 virion.Disrupting Vpu-tetherin interactions may provide a promising new target for antiretroviral the...Background:HIV-1 Vpu acts by counteracting the tethering function of tetherin and resulting in the release of HIV-1 virion.Disrupting Vpu-tetherin interactions may provide a promising new target for antiretroviral therapy.Methods:Polypeptides that covered the amino acid sequence on the interface of Vpu-tetherin complex were designed.Phenotypic susceptibilities and cellular toxicities to the polypeptides were measured.The mechanisms of the anti-HIV-1 polypeptides were determined by the Western blot analysis and laser confocal scanning.Seven 20-mer polypeptides from wild-type Vpu amino acid sequence were designed.Results:We report the design and identification of 3 novel anti-HIV-1 polypeptides that derived from Vpu se-quence which can efficiently inhibit HIV-1 infection.A pilot mechanism study showed that the active polypeptide could counteract Vpu-mediated tetherin downregulation.Laser confocal image scanning study showed that the polypeptides bound on the cell surface with a receptor specific binding manner,which may target tetherin that expressed on cell surface.Conclusion:Our work provided first evidence that counteracting Vpu-mediated tetherin downregulation could be a target for novel anti-HIV-1 drug design.Future works to provide direct evidence of inhibitors interact with teth-erin at atomic resolution and the development of small molecules inhibitors targeting Vpu-tetherin interactions may open a new avenue for novel antiretroviral therapy.展开更多
Human endogenous retrovirus(HERV)gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes,accounting for approximately 8%-9%of ...Human endogenous retrovirus(HERV)gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes,accounting for approximately 8%-9%of the human genome.Most integrated HERVs have lost their coding capacity and remain silent due to frame shifts,mutations,and sequence deletions or insertions over the millions of years,but their expression is highly regulated by epigenetic and host defense mechanisms.However,there are still some HERV genes that have intact open reading frames due to recent integration into the human genome or positive selective pressure.The abnormal activation of HERVs may contribute to diseases or their pathology,such as malignant tumors,autoimmune diseases,and nervous system diseases.The occurrence and development of hematological malignant tumors(HMTs)is a complex process involving interactions of multiple genetic and environmental factors.The abnormal activation of HERVs may contribute to the pathology of HMTs via indirect mechanisms.In this review,we address the discovery of endogenous retroviruses in vertebrates,and the classification and genomic structure of HERVs.Among HERV family members,HERV-K is the latest type of HERV integrated into the human genome and it has the strongest transcriptional activity.We explore the currently known expression of HERV-K proto-oncogenes in HMTs and further address potential research and therapeutic approaches.However,much remains to be learned about not only the impact of HERVs on the occurrence of HMTs,but also the potential value of HERVs as diagnostic and therapeutic targets for HMTs.展开更多
基金supported by the Applied Basic Research Programs of the Science and Technology Department of Yunnan Province(Grant No.2013FZ217)National Key S&T Special Projects on Major Infectious Diseases(Grant No.2012ZX10001-002)approved by the ethics committees of Health Department of Yunnan Province
文摘Dear Editor,Recombination contributes greatly to the diversity of human immunodeficiency virus type 1（HIV-1）.A large number of recombinant strains have been found in China,particularly in Yunnan,which is considered the HIV-1 epicenter of China.Surveillance of unique recombinant forms is helpful for prediction of new circulating recombinant forms.
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.
基金This work was supported by the National Grand Fundamental Research 973 Program of China （No. 2006CB504206） and the National Natural Science Foundation of China （No. 30830088）.
文摘Background Virus with nucleoside reverse transcriptase inhibitors （NRTIs） or nonnucleoside reverse transcriptase inhibitors （NNRTIs） resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine （3TC） or nevirapine （NVP） resistant mutations. Methods 3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay. Results 3TC-resistant （M184I mutation） and NVP-resistant （Y181I mutation） virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages. Conclusions The NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.
基金Supported by the grants from the National Key Research and Development Project(No.2017YFB1304300)Conversion Fund of PLA General Hospital(No.2017tm-018)the Clinical Research Support Fund of PLA General Hospital(No.2017fc-tsys-2013).
文摘Background:The casein kinase 2-interacting protein-1(CKIP-1)is important in the development of osteoblasts and cardiomyocytes.However,the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells(MSCs)remain unclear.This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation.Methods:Bone marrow MSCs of CKIP-1 wild type(WT)and knockout(KO)mice were cultivated in vitro.Cell phenotype was analyzed by flow cytometry,colony formation was detected to study the proliferative ability.Osteogenic and adipogenic induction were performed.The osteogenic ability was explored by alizarin red staining,alkaline phosphatase(ALP)staining and ALP activity detection.Quantitative real-time polymerase chain reaction(qRT-PCR)was carried out to determine the mRNA expression levels of osteoblast marker genes.The adipogenic ability was detected by oil red O staining.Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume(BV/TV),bone surface area fraction/trabecular BV,trabecular number(Tb.N),and trabecular spacing(Tb.sp).Interleukin(IL)-1b was injected on WT mice of 2 months old and 18 months old,respectively.Difference in CKIP-1 expression was detected by RT-PCR and western blot.The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot.Results:ALP assays,alizarin red staining,and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis.Micro-computed tomography detection showed that among 18-month-old mice,CKIP-1 KO mice presented significantly higher bone mass compared withWTmice(P=0.02).No significant difference was observed in 2-month-old mice.In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice(4.3-fold increase at themRNA level,P=0.04).Finally,the expression levels of CKIP-1 in bone marrow(3.2-fold increase at themRNA level,P=0.03)and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1b.Conclusions:CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects.Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.
文摘Background:HIV-1 Vpu acts by counteracting the tethering function of tetherin and resulting in the release of HIV-1 virion.Disrupting Vpu-tetherin interactions may provide a promising new target for antiretroviral therapy.Methods:Polypeptides that covered the amino acid sequence on the interface of Vpu-tetherin complex were designed.Phenotypic susceptibilities and cellular toxicities to the polypeptides were measured.The mechanisms of the anti-HIV-1 polypeptides were determined by the Western blot analysis and laser confocal scanning.Seven 20-mer polypeptides from wild-type Vpu amino acid sequence were designed.Results:We report the design and identification of 3 novel anti-HIV-1 polypeptides that derived from Vpu se-quence which can efficiently inhibit HIV-1 infection.A pilot mechanism study showed that the active polypeptide could counteract Vpu-mediated tetherin downregulation.Laser confocal image scanning study showed that the polypeptides bound on the cell surface with a receptor specific binding manner,which may target tetherin that expressed on cell surface.Conclusion:Our work provided first evidence that counteracting Vpu-mediated tetherin downregulation could be a target for novel anti-HIV-1 drug design.Future works to provide direct evidence of inhibitors interact with teth-erin at atomic resolution and the development of small molecules inhibitors targeting Vpu-tetherin interactions may open a new avenue for novel antiretroviral therapy.
文摘Human endogenous retrovirus(HERV)gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes,accounting for approximately 8%-9%of the human genome.Most integrated HERVs have lost their coding capacity and remain silent due to frame shifts,mutations,and sequence deletions or insertions over the millions of years,but their expression is highly regulated by epigenetic and host defense mechanisms.However,there are still some HERV genes that have intact open reading frames due to recent integration into the human genome or positive selective pressure.The abnormal activation of HERVs may contribute to diseases or their pathology,such as malignant tumors,autoimmune diseases,and nervous system diseases.The occurrence and development of hematological malignant tumors(HMTs)is a complex process involving interactions of multiple genetic and environmental factors.The abnormal activation of HERVs may contribute to the pathology of HMTs via indirect mechanisms.In this review,we address the discovery of endogenous retroviruses in vertebrates,and the classification and genomic structure of HERVs.Among HERV family members,HERV-K is the latest type of HERV integrated into the human genome and it has the strongest transcriptional activity.We explore the currently known expression of HERV-K proto-oncogenes in HMTs and further address potential research and therapeutic approaches.However,much remains to be learned about not only the impact of HERVs on the occurrence of HMTs,but also the potential value of HERVs as diagnostic and therapeutic targets for HMTs.
