Human immunodeficiency virus (HIV) infection is endemic in South Africa. Non-Hodgkin lymphoma (NHL) occurs with increased frequency in HIV seropositive individuals. The increase in NHL has been more marked in the last...Human immunodeficiency virus (HIV) infection is endemic in South Africa. Non-Hodgkin lymphoma (NHL) occurs with increased frequency in HIV seropositive individuals. The increase in NHL has been more marked in the last decade, with HIV being the major contributor to this increase. More than 70% of the adult NHL patients at Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, are HIV seropositive. In addition, HIV has impacted on the clinical presentation—being more aggressive and atypical. Histologically, HIV-NHL typically manifests as B-cell, high grade lymphomas, including diffuse large B-cell lymphoma (DLBCL);Burkitt lymphoma (BL);B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL and plasmablastic lymphoma. The latter two entities, which were previously rare or unknown, have gained prominence in the last decade, occurring primarily in HIV seropositive individuals. HIV-NHL, being associated with all these adverse prognostic factors results in a poorer overall survival.展开更多
The envelope protein （Env） of lentiviruses such as HIV, SIV, FIV and EIAV is larger than that of other retroviruses. The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this vi...The envelope protein （Env） of lentiviruses such as HIV, SIV, FIV and EIAV is larger than that of other retroviruses. The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this virus, demonstrating that envelope is crucial for vaccine. We compared Env variation of the four kinds of lentiviruses. Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest. EIAV had the shortest Env length and the least number of potential N-linked glyeosylation sites （PNGS） as well as glyeosylation density compared to various immunodefieiency viruses. However, HIV had the longest Env length and the most PNGS. Moreover, the alignment of HIV and SIV showed that PNGS were primarily distributed within extraeellular membrane protein gp120 rather than transmembrane gp41. It implies that the size difference among these viruses is associated with a lentivirus specific function and also the diversity of env. There arc low levels of modification of glycosylation sites of Env and selection of optimal protective epitopes might be useful for development of an effective vaccine against HIV/AIDS.展开更多
Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome...Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level. Methods Twenty-five HIV-I B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef〉Vpr〉Gag〉Pol〉Vpu〉Env〉Rev〉Vif〉Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-γ production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-1-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.展开更多
Gene therapy is one of several approaches that are being tested in the search for an effective anti HIV treatment. In this strategy, a “resistant” gene would be introduced into target ...Gene therapy is one of several approaches that are being tested in the search for an effective anti HIV treatment. In this strategy, a “resistant” gene would be introduced into target cells, rendering them resistance to the infection of HIV. The HIV 1 Tat protein transactivate HIV 1 gene expression at the transcriptional level by interacting with its response element(TAR) in the long terminal repeat(LTR). Previously, we have shown that antisense polyTAR Core RNAs can inhibit the transactivation of HIV 1 Tat protein in transiently transfected Jurkat cells. To determine whether this antisense polyTAR Core RNAs could inhibit HIV 1 replication in CD 4+ T cells, we transfected the antisense polyTAR Core gene to MT4 cells and challenged them with HIV 1 SF33 strain. Levels of HIV 1 p24gag antigen were reduced more than 4 fold in cultures of the transduced MT4/LR cells infected with HIV 1SF33 strain. In contrast, cultures of nontransduced MT4 cells and control LX vector transduced MT4/LX cells infected with the same viruses had high levels of HIV 1 p24gag. Our work showed that antisense polyTAR Core RNAs were able to inhibit HIV 1 replication in CD 4+ T cells, and could be used as resistance gene in further studying for gene therapy against HIV 1.展开更多
The infection due to human immunodeficiency virus(HIV) is characterized by the progressive reduction of CD4+ T lymphocytes and the compromise of other cell lines of the immune system, resulting in immunosuppression. I...The infection due to human immunodeficiency virus(HIV) is characterized by the progressive reduction of CD4+ T lymphocytes and the compromise of other cell lines of the immune system, resulting in immunosuppression. In this context, autoimmune diseases could be considered contradictory, however, cases of autoimmune diseases during this infection have been described, including autoimmune hepatitis(AIH), which is uncommon and has few case reports within medical literature, none of them from Latin America. In this case report where a patient with an HIV infection on combined antiretroviral treatment developed acute elevation of transaminases, hyperbilirubinemia, and deterioration in hepatic synthetic function. Although initially an antiretroviral drug-induced liver injury was suspected, during the study a diagnosis of autoimmune hepatitis was proven, which required treatment with corticosteroid and azathioprine, obtaining a satisfactory response and managing to continue the antiretroviral therapy. Autoimmune diseases in HIV infection must be taken into account. In the case of hepatitis in patients with HIV on antiretroviral treatment, the differentiation between viral hepatitis caused by autoimmune diseases or medications is essential to establish an adequate treatment, and avoid the suspension of the antiretroviral therapy.展开更多
Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as v...Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.展开更多
Although the distribution of cytomegalovirus (CMV) infection has a wide regional variation, it is more common in Africa and Asia with high prevalence approaching 100% in some communities. CMV is a frequent opportunist...Although the distribution of cytomegalovirus (CMV) infection has a wide regional variation, it is more common in Africa and Asia with high prevalence approaching 100% in some communities. CMV is a frequent opportunistic infection and major cause of morbidity and mortality among HIV patients with severe immunosuppression. It can be contracted from body fluid, including saliva, urine, blood, cervical secretions, and semen. CMV seropositivity is considered the best laboratory measure of past infection. We determined the prevalence of CMV and the risk factors associated with its acquisition in a population of HIV positive patients. Anti-CMV IgG seroprevalence was 100% among HIV infected subjects and 98.6% among controls. Having multiple sexual partners and traditional practices were identified as risk factors associated with risk of contracting CMV infection.展开更多
Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to invest...Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness.Methods:A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders(IRs)(CD4^(+)T-cell count>500)and immunological non-responders(INRs)(CD4^(+)T-cell count<300)was conducted.The transcriptomic profiles were used to identify distinct cell subpopulations,marker genes,and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness.Results:Among the cellular subpopulations analyzed,the ratios of monocytes,CD16^(+)monocytes,and exhausted B cells demonstrated the most substantial differences between INRs and IRs,with fold changes of 39.79,11.08,and 2.71,respectively.In contrast,the CD4^(+)T cell ratio was significantly decreased(0.39-fold change)in INRs compared with that in IRs.Similarly,the ratios of natural killer cells and terminal effector CD8^(+)T cells were also lower(0.37-fold and 0.27-fold,respectively)in the INRs group.In addition to several well-characterized immune cell-specific markers,we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus(HIV)replication.Notably,ISG15,IFITM3,PLSCR1,HLA-DQB1,CCL3L1,and DDX5,which have been demonstrated to influence HIV replication through their interaction with viral proteins,emerged as significant monocyte marker genes.Furthermore,the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication.Conclusions:We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs.Host genes associated with HIV replication were identified as markers of,and were found to be differentially expressed in,different types of immune cells.展开更多
文摘Human immunodeficiency virus (HIV) infection is endemic in South Africa. Non-Hodgkin lymphoma (NHL) occurs with increased frequency in HIV seropositive individuals. The increase in NHL has been more marked in the last decade, with HIV being the major contributor to this increase. More than 70% of the adult NHL patients at Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, are HIV seropositive. In addition, HIV has impacted on the clinical presentation—being more aggressive and atypical. Histologically, HIV-NHL typically manifests as B-cell, high grade lymphomas, including diffuse large B-cell lymphoma (DLBCL);Burkitt lymphoma (BL);B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL and plasmablastic lymphoma. The latter two entities, which were previously rare or unknown, have gained prominence in the last decade, occurring primarily in HIV seropositive individuals. HIV-NHL, being associated with all these adverse prognostic factors results in a poorer overall survival.
基金Natural Science Foundation of China(30970162)Tianjin Municipal Science and Technology Foundation(08ZCGHHZ01800)
文摘The envelope protein （Env） of lentiviruses such as HIV, SIV, FIV and EIAV is larger than that of other retroviruses. The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this virus, demonstrating that envelope is crucial for vaccine. We compared Env variation of the four kinds of lentiviruses. Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest. EIAV had the shortest Env length and the least number of potential N-linked glyeosylation sites （PNGS） as well as glyeosylation density compared to various immunodefieiency viruses. However, HIV had the longest Env length and the most PNGS. Moreover, the alignment of HIV and SIV showed that PNGS were primarily distributed within extraeellular membrane protein gp120 rather than transmembrane gp41. It implies that the size difference among these viruses is associated with a lentivirus specific function and also the diversity of env. There arc low levels of modification of glycosylation sites of Env and selection of optimal protective epitopes might be useful for development of an effective vaccine against HIV/AIDS.
文摘Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level. Methods Twenty-five HIV-I B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef〉Vpr〉Gag〉Pol〉Vpu〉Env〉Rev〉Vif〉Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-γ production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-1-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.
文摘Gene therapy is one of several approaches that are being tested in the search for an effective anti HIV treatment. In this strategy, a “resistant” gene would be introduced into target cells, rendering them resistance to the infection of HIV. The HIV 1 Tat protein transactivate HIV 1 gene expression at the transcriptional level by interacting with its response element(TAR) in the long terminal repeat(LTR). Previously, we have shown that antisense polyTAR Core RNAs can inhibit the transactivation of HIV 1 Tat protein in transiently transfected Jurkat cells. To determine whether this antisense polyTAR Core RNAs could inhibit HIV 1 replication in CD 4+ T cells, we transfected the antisense polyTAR Core gene to MT4 cells and challenged them with HIV 1 SF33 strain. Levels of HIV 1 p24gag antigen were reduced more than 4 fold in cultures of the transduced MT4/LR cells infected with HIV 1SF33 strain. In contrast, cultures of nontransduced MT4 cells and control LX vector transduced MT4/LX cells infected with the same viruses had high levels of HIV 1 p24gag. Our work showed that antisense polyTAR Core RNAs were able to inhibit HIV 1 replication in CD 4+ T cells, and could be used as resistance gene in further studying for gene therapy against HIV 1.
文摘The infection due to human immunodeficiency virus(HIV) is characterized by the progressive reduction of CD4+ T lymphocytes and the compromise of other cell lines of the immune system, resulting in immunosuppression. In this context, autoimmune diseases could be considered contradictory, however, cases of autoimmune diseases during this infection have been described, including autoimmune hepatitis(AIH), which is uncommon and has few case reports within medical literature, none of them from Latin America. In this case report where a patient with an HIV infection on combined antiretroviral treatment developed acute elevation of transaminases, hyperbilirubinemia, and deterioration in hepatic synthetic function. Although initially an antiretroviral drug-induced liver injury was suspected, during the study a diagnosis of autoimmune hepatitis was proven, which required treatment with corticosteroid and azathioprine, obtaining a satisfactory response and managing to continue the antiretroviral therapy. Autoimmune diseases in HIV infection must be taken into account. In the case of hepatitis in patients with HIV on antiretroviral treatment, the differentiation between viral hepatitis caused by autoimmune diseases or medications is essential to establish an adequate treatment, and avoid the suspension of the antiretroviral therapy.
基金Chongqing Professional Talents Plan,Grant/Award Number:cstc2022ycjh-bgzxm0048Fundamental Research Funds for the Central Universities,Grant/Award Number:2022CDJYGRH-001Natural Science Foundation of Chongqing,China,Grant/Award Number:CSTB2022NSCQ-MSX1150。
文摘Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.
文摘Although the distribution of cytomegalovirus (CMV) infection has a wide regional variation, it is more common in Africa and Asia with high prevalence approaching 100% in some communities. CMV is a frequent opportunistic infection and major cause of morbidity and mortality among HIV patients with severe immunosuppression. It can be contracted from body fluid, including saliva, urine, blood, cervical secretions, and semen. CMV seropositivity is considered the best laboratory measure of past infection. We determined the prevalence of CMV and the risk factors associated with its acquisition in a population of HIV positive patients. Anti-CMV IgG seroprevalence was 100% among HIV infected subjects and 98.6% among controls. Having multiple sexual partners and traditional practices were identified as risk factors associated with risk of contracting CMV infection.
基金supported by the Joint Research Project of Health and Education in Fujian Province(No.2019-WJ-15)Natural Science Foundation of Fujian Province(Nos.2021J011295 and 2020J011165)Fujian Chinese Traditional Medicine University research funding(No.XB2020147)
文摘Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness.Methods:A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders(IRs)(CD4^(+)T-cell count>500)and immunological non-responders(INRs)(CD4^(+)T-cell count<300)was conducted.The transcriptomic profiles were used to identify distinct cell subpopulations,marker genes,and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness.Results:Among the cellular subpopulations analyzed,the ratios of monocytes,CD16^(+)monocytes,and exhausted B cells demonstrated the most substantial differences between INRs and IRs,with fold changes of 39.79,11.08,and 2.71,respectively.In contrast,the CD4^(+)T cell ratio was significantly decreased(0.39-fold change)in INRs compared with that in IRs.Similarly,the ratios of natural killer cells and terminal effector CD8^(+)T cells were also lower(0.37-fold and 0.27-fold,respectively)in the INRs group.In addition to several well-characterized immune cell-specific markers,we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus(HIV)replication.Notably,ISG15,IFITM3,PLSCR1,HLA-DQB1,CCL3L1,and DDX5,which have been demonstrated to influence HIV replication through their interaction with viral proteins,emerged as significant monocyte marker genes.Furthermore,the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication.Conclusions:We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs.Host genes associated with HIV replication were identified as markers of,and were found to be differentially expressed in,different types of immune cells.
