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.
Humans ; Acquired Immunodeficiency Syndrome ; Transcriptome/genetics* ; HIV ; HIV Infections/genetics* ; Leukocytes, Mononuclear/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Virus Replication ; Membrane Proteins/metabolism* ; RNA-Binding Proteins/metabolism*

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.
Humans ; Female ; HIV Infections ; Acquired Immunodeficiency Syndrome ; Infectious Disease Transmission, Vertical ; Nomograms ; Selenoproteins/genetics*

Objective: To investigate the related factors associated with the structure of the gut microbial community in HIV infection/AIDS cases (HIV/AIDS) in Henan province. Methods: The convenience sampling method was used to select 122 cases who were receiving Antiviral Treatment (ART) or ART-naive in Henan. Whole blood and stool specimens were collected. Genomic DNA of stool samples was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using Illumina NovaSeq 6000 high-throughput sequencing system. The analysis was performed mainly at the genus level, and the 30 genera with the highest abundance were selected as a measure of the gut microbial community structure. The correlation between community structure and related factors was analyzed using redundancy analysis and Envfit function. Results: 122 cases were finally completed sequencing and analysis, the average BMI was (23.62±2.78) kg/m² and the average age was (47±13) years. Among them, male accounted for 66.39% (81/122), and heterosexual transmission route constituted the largest ratio, accounting for 51.64% (63/122). 36 cases were treatment naive (29.51%, 36/122). The top five dominant genera of the total population (122 cases) were Prevotella, Roseburia, Megamonas, Bacteroides and Faecalibacterium and the top five dominant genera of the ART population (86 cases) were Prevotella, Megamonas, Bacteroides, Roseburia and Faecalibacterium. The top five dominant genera of the ART-naive population (36 cases) appeared as Prevotella, Faecalibacterium, Roseburia, Bacteroides and Megamonas. In the total population, ART (P<0.001) was the most significant factors of community structure. Other significant factors were: duration of diagnosis (P=0.009), viral load (P=0.022) and anti-HCV (P=0.018). ART was positively correlated with Megamonas and negatively correlated with Prevotella, Roseburia and Faecalibacterium, while the other three factors of duration of diagnosis, viral load and anti-HCV were positively correlated with Prevotella, Roseburia and Faecalibacterium and negatively correlated with Megamonas. In the ART-naive population, duration of diagnosis (P=0.003) were the factors significantly associated with community structure. Duration of diagnosis was positively correlated with Roseburia, Faecalibacterium, Megamonas and Prevotella and negatively correlated with Bacteroides. Conclusion: ART and duration of diagnosis were factors significantly associated with gut microbial community structure and had a significant impact on multiple high-abundance genera.
Acquired Immunodeficiency Syndrome/epidemiology* ; Adult ; Gastrointestinal Microbiome/genetics* ; HIV Infections/epidemiology* ; Humans ; Male ; Microbiota ; Middle Aged ; RNA, Ribosomal, 16S/genetics*

The aim of this paper was to study the influence of triptolide in the immune response pathways of acquired immune deficiency syndrome( AIDS). Target proteins of triptolide and related genes of AIDS were searched in PubChem and Gene databases on line. Molecular networks and canonical pathways comparison analyses were performed by bioinformatics software( IPA). There were 15 targets proteins of triptolide and 258 related genes of AIDS. Close biological relationships of molecules of triptolide and AIDS were established by networks analysis. There were 21 common immune response pathways of triptolide and AIDS,including neuroinflammation signaling pathway,Th1 and Th2 activation pathway and role of pattern recognition receptors in recognition of bacteria and viruses. Triptolide stimulated immune response pathways by the main molecules of IFNγ,JAK2,NOD1,PTGS2,RORC. IFNγ is the focus nodes of triptolide and AIDS,and regulates genes of AIDS directly or indirectly. Triptolide may against AIDS by regulating molecules IFNγ in immune response pathways.
Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; Computational Biology ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Gene Regulatory Networks ; Humans ; Interferon-gamma ; genetics ; Phenanthrenes ; pharmacology ; Receptors, Pattern Recognition ; immunology ; Signal Transduction ; T-Lymphocytes ; immunology

Acquired Immunodeficiency Syndrome ; genetics ; therapy ; CRISPR-Cas Systems ; Genetic Therapy ; methods ; Humans

In this study, five rhesus macaques were inoculated intravenously with SIVmac251 to establish a model of simian autoimmune deficiency syndrome (SAIDS). Peripheral blood samples were collected at different time points to monitor changes in the total T cell number and T lymphocyte subset. Plasma viral loads, cytokine expression levels and anti-SIV antibody levels were also assayed to acquire certain basic indexes to evaluate disease progression in the rhesus macaque SAIDS model. During the acute stage of infection, plasma viral loads reached a peak at week 1 post-inoculation and lasted for approximately 3 to 44 weeks. The CD3+ CD4+ T lymphocyte count in peripheral blood also transitorily decreased. During the same period, the level of interferon-gamma show an increasing trend, whereas IL-12 levels decreased; IL-2, IL-4, IL-10 and TNF-alpha were maintained at normal levels or could not be detected. During the asymptomatic and ARC phases, plasma viral loads persisted above 10(4) RNA copies/mL and either increased or declined during the later stages of disease; CD3+ CD4+ counts showed a steadily declining trend and the ratio of CD4 to CD8 decreased during late-stage disease. Moreover, antibodies against viral proteins were detected in the plasma and showed a significant increasing trend, while there were no apparently changes in the levels of IFN-gamma, IL-12, IL-2, IL-4, IL-10 and TNF-alpha. In conclusion, the characteristics of the SIV animal models in our study are similar to those of patients with AIDS. Therefore, the rhesus macaque SIVmac251 infection models can be applied for further studies into AIDS.
Animals ; Antibodies, Viral ; blood ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; virology ; Cytokines ; genetics ; immunology ; Disease Models, Animal ; HIV Infections ; genetics ; immunology ; virology ; HIV-1 ; physiology ; Humans ; Macaca mulatta ; Male ; Simian Acquired Immunodeficiency Syndrome ; genetics ; immunology ; virology ; Simian Immunodeficiency Virus ; physiology ; Viral Load

OBJECTIVETo discuss the drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution.

METHODPBMCs were isolated from 37 cases of AIDS patients failure to immune reconstitution before and after treatment with Immune 2 and 15 cases of HIV negative healthy donors. The human gene TCRVbeta CDR3 diversity quantitative detection reagent box were used, and mapped the distribution of gene scanning and calculated different CDR3 fragme of each Vbeta family size.

RESULT(1) Gaussian distribution of TCRVbeta families in patients with incomplete immune reconstitution after one year of HAART, had been broken with the occurrence of the offset TCR lineage. After six months of treatment of traditional Chinese medicine combined HAART, the TCR lineage has been partially restored. (2) Evaluated by the D (distance) value calculated by a quantitative analysis software which the kit provides, there were no significant difference in D value change between the two groups, but with traditional Chinese medicine can reduce the data variability. (3) CD4+ T cell counts had a significant correlation (r = -0.772, P = 0.000) with TCRVbeta genetic diversity.

CONCLUSIONStudy of the mechanism showed oligoclonal of TCRVbeta family can get recovery in some degrees after treated by Immune 2 plus HAART, suggesting that the medicine may promote T-cell receptor gene rearrangement, helping immune cells to effectively identify the virus to reduce T-cell apoptosis.

Acquired Immunodeficiency Syndrome ; drug therapy ; genetics ; immunology ; Anti-HIV Agents ; pharmacology ; therapeutic use ; Antiretroviral Therapy, Highly Active ; Genetic Variation ; drug effects ; Humans ; Receptors, Antigen, T-Cell ; genetics ; T-Lymphocytes ; drug effects ; immunology ; metabolism

OBJECTIVETo discuss the drug intervention in diversity changes of TCRVbeta gene in AIDS patients with incomplete immune reconstitution.

METHODPBMCs were isolated from 37 cases of AIDS patients failure to immune reconstitution before and after treatment with immune 2 and 15 cases of HIV negative healthy donors. The human gene TCRVbeta CDR3 diversity quantitative detection reagent box were used, and mapped the distribution of gene scanning and calculated different CDR3 fragme of each Vbeta family size.

RESULTCompared with the normal group, there appeared some single or oligoclonal amplification of Vbeta CDR3 region in the patients, which were improved or recovered after treatment. Among them, D value of four families (9, 11, 21, 22 ) decreased after treatment in both groups. The decrease in family 21 and 22 was significant (P < 0.05) in treatment group compared with the control group. And family 18 was decreased in treatment group and increased significantly in control group (P < 0.05).

CONCLUSIONStudy of the mechanism showed oligoclonal of TCRVbeta family can get recovery in some degrees after treated by Immune 2 plus HAART, suggesting that the medicine may promote T-cell receptor gene rearrangement, helping immune cells to effectively identify the virus to reduce T-cell apoptosis.

Acquired Immunodeficiency Syndrome ; drug therapy ; genetics ; immunology ; Antiretroviral Therapy, Highly Active ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Genetic Variation ; drug effects ; Humans ; Receptors, Antigen, T-Cell ; genetics

OBJECTIVETo analyze the molecular epidemiological characteristics of HIV-1 subtype CRF01_AE strains being prevailed among HIV/AIDS in Zhejiang province in 2009.

METHODSA total of 303 subjects were identified by stratified random sampling among HIV infected individuals in Zhejiang province in 2009. Gag fragments of the HIV-1 strains were amplified by nested polymerase chain reaction from the DNA extracted from whole blood of HIV-1 infected individuals. PCR products were sequenced and analyzed by phylogenetic method.

RESULTSA total of 132 HIV-1 subtype CRF01_AE sequences were identified from the 225 samples that sequenced successfully, accounting for 58.67% (132/225). A total of 90.91% (120/132) CRF01_AE strains infected HIV/AIDS were transmitted mainly by sexual contacts. A total of 65.91% (87/132) of the cases infected by heterosexual route and 25.00% (33/132) by homosexual route. There were three main clusters in the phylogenetic tree. Pairwise DNA distance within three groups was 0.037 ± 0.011, 0.034 ± 0.008 and 0.047 ± 0.010, which has statistical significance (P < 0.05). Distribution of the sequence of homosexual behavior infected individuals was relatively concentrated in clusters one (96.97%, 32/33), and crossed with heterosexual behavior infectors, and presented the close relations with strains from Jiangsu province, Zhengzhou of Henan province, Liaoning province, Shijiazhuang of Hebei province.

CONCLUSIONThe CRF01_AE strains were the dominant subtypes among HIV infected individuals. The majority of the CRF01_AE infected cases had high risk sexual behavior. The heterosexual infected cases were more than homosexual cases. The circulating status of CRF01_AE strains in homosexual population was relatively independent, but also had evidence of transmission from man who have sex with man to heterosexual population.

Acquired Immunodeficiency Syndrome ; epidemiology ; virology ; Adolescent ; Adult ; China ; epidemiology ; Female ; Genetic Variation ; HIV-1 ; classification ; genetics ; Humans ; Male ; Middle Aged ; Molecular Epidemiology ; Phylogeny ; Young Adult

OBJECTIVETo investigate drug resistance status in patients with highly active antiretroviral therapy (HAART) in Shandong province.

METHODSA total of 758 patients were separated from the anticoagulatory whole blood during May and October in 2011. The entire protease gene and part of the reverse transcriptase gene were amplified by RT-PCR and nest-PCR in the samples with viral load larger than 1000 copies/ml, then sequenced the gene fragments. Mutation of drug resistant gene and drug susceptibility was analyzed by the online tool HIV db program developed by Stanford University.

RESULTSThe rate of virologic failure in patients was 9.1% (69/758). A total of 53 gene sequences that acquired were used for genotypic resistance analysis. A total of 23 patients were indicated drug resistance with the total of 3.1% (23/742). Drug resistance rates of nucleotide reverse transcriptase inhibitor (NRTI) and non-NRTI(NNRTI) were 2.4% (18/742) and 3.0% (22/742), respectively, and the primary mutation types of drug resistance were M184V and Y181C for NRTI and NNRTI, with no resistance to protease inhibitor (PI). In the 23 patients indicated drug resistance, 78.3% (18/23) were NRTI resistance, 95.7% (22/23) were NNRTI resistance and 73.9% (17/23) dual NRTI and NNRTI resistance.

CONCLUSIONThe presence of drug resistant gene in HIV strains among AIDS patients with HAART in Shandong province was at low level, but mutation diversity was found in drug resistant gene.

Acquired Immunodeficiency Syndrome ; drug therapy ; virology ; Adolescent ; Adult ; Aged ; Antiretroviral Therapy, Highly Active ; Drug Resistance, Viral ; genetics ; Female ; Genes, Viral ; Genotype ; HIV-1 ; drug effects ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Sequence Analysis ; Viral Load ; Young Adult