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

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*

BACKGROUNDPenicillium marneffei (P. marneffei) is an emerging pathogenic fungus that can cause invasive mycosis in patients with AIDS. The epidemiological features of P. marneffei infection in AIDS patients in Guangdong province remain unclear so far. This study aimed to investigate the genetic diversity within a population of 163 P. marneffei isolates obtained from AIDS patients and search for the dominant clinical strains in Guangdong province.

METHODSOne hundred and sixty-three P. marneffei isolates obtained from AIDS patients in Guangdong province during January 2004 and December 2009 were studied by randomly amplified polymorphic DNA (RAPD) using two random primers (H2 and H22). The degree of similarity between samples was calculated through similarity coefficients from RAPD fragment data and the dendrogram was assessed using the unweighted pair group method with arithmetic mean (UPGMA).

RESULTSTwo primers showed a high degree of discrimination and good stability. Primer H2 yielded eight different patterns (H2-1 to H2-8) among 163 isolates with the discriminatory power being 0.413. Primer H22 identified seven types (H22-1 to H22-7) among 163 isolates with the discriminatory power being 0.467. Genetic similarity coefficients based on RAPD data among 163 P. marneffei isolates ranged from 0.681 to 0.957, 61.96% of which were no less than 0.83. The discriminatory power of the two primers was 0.524. One hundred and sixty-three P. marneffei isolates were clustered into nine distinct groups (groups I to IX) at the similarity coefficient value of 0.83 and group I was the most common, including 101 strains (61.96%).

CONCLUSIONThe RAPD analyses could provide important information as to the degree of genetic diversity and the relationship among clinical P. marneffei isolates, revealing genetic polymorphism and dominant strains.

Acquired Immunodeficiency Syndrome ; microbiology ; Genetic Variation ; genetics ; Humans ; Penicillium ; classification ; genetics ; Random Amplified Polymorphic DNA Technique ; methods

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*

OBJECTIVESince the advent in 2004 of highly active antiretroviral therapy (HAART) in Liaoning, a dramatic improvement had been seen in the number of patients attaining undetectable viral loads (92/104), but the extent of mutation diversity on human immunodeficiency virus 1 (HIV-1) and the prevalence of drug resistance had remained elusive. This study aimed to analyze both HIV-1 mutation profiles and prevalence related to antiretroviral resistance following therapeutic failure.

METHODSA total of 104 blood samples circling Liaoning from HAART-treated between 2004 and 2008 were studied. Patients' CD(4)(+) T-cell count and viral load were determined. HIV-1 pol (PR and part of RT) gene fragments were amplified from patients' plasma by reverse transcriptase polymerase chain reaction (RT-PCR) and nest-PCR, subsequently sequenced and analyzed.

RESULTSCD(4)(+) T cell numbers and viral replication capacity were assessed. 88.4% (92/104) of the patients were successful after initial non-suppressive NRTI & NNRTI-based HAART regimens. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (6/104) drug-resistance mutations than those on nucleoside reverse transcriptase inhibitor (NRTI) regimens did (5/104). No protease-inhibitor (PI) drug resistance mutations developed. The whole rate of drug resistance mutations was about 6.73%. Subjects developing NNRTI-resistance (NNRTI-R) seemed more likely to develop drug-resistant viremia than with NRTI-based HAART.

CONCLUSIONThis finding might have implications in which that the prevalence of drug-resistance mutations was low but remained risk of transmission in HIV-infected therapeutic failure. Meanwhile, data from the present study showed that there was a high frequency of primary mutations, which offered resistance to nrti and nnrti. Monitoring patients with treatment failure seems an important tool in helping the physicians to improve their treatment schedule and to carry out epidemiological surveillance programs.

Acquired Immunodeficiency Syndrome ; drug therapy ; epidemiology ; virology ; China ; epidemiology ; Drug Resistance, Viral ; genetics ; HIV-1 ; drug effects ; genetics ; Humans ; Molecular Epidemiology ; RNA, Viral ; genetics ; Viral Load

OBJECTIVETo study the polymorphisms and secondary structure of human immunodeficiency virus (HIV-1) tat exon 1 among subtype B' and B'/C HIV-1 infected people in China and to explore the relationship between the polymorphism of tat exon 1 and the disease progression.

METHODS8 subtype B' and 5 B'/C HIV-1 infected patients with slow disease progression were selected from Liaoning, Jilin and Yunnan province. 26 subtype B' and 9 B'/C HIV-1 infected patients with similar sex, age but with typical disease progression were selected. Provirus was extracted from the whole blood. The gene sequences of the Tat exon 1 were amplified by nest-polymerase chain reaction (nest-PCR). Products were purified and sequenced directly. The sequences were aligned, translated, amino acid substitution were analyzed and secondary structures were predicted.

RESULTSMany amino acid substitution could be found in the exon 1 of Tat in HIV-1 subtype B' and B'/C recombinant strain infected persons with different disease progression except A58T,none of them showed definitely relationship with HIV viral load and disease progression. 23N, 31S, 32Y and 46F were subtype-specific substitutions. No characteristic secondary structure of exon 1 of Tat was found.

CONCLUSIONSome of the mutations of tat exon 1 might be related to HIV viral load and disease progression. However, there was no relationship found between the secondary structure of Tat protein and the disease progression.

Acquired Immunodeficiency Syndrome ; genetics ; pathology ; Amino Acid Substitution ; Disease Progression ; Exons ; genetics ; Genes, tat ; genetics ; HIV Infections ; genetics ; pathology ; Human Immunodeficiency Virus Proteins ; genetics ; Humans ; Polymorphism, Genetic ; 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.

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 establish genetic method in detecting Cryptosporidium parvum and Giardia lamblia which often coinfected with AIDS patients.

METHODSCryptosporidium oocysts and Giardia cysts were isolated and purified from fecal samples of the individuals infected with C. parvum and G. lamblia, respectively. Genomic DNAs were extracted. Two pairs of specific primers were designed or synthesized according to the 18S rRNA gene from C. parvum or the triose phosphate isomerase (tim ) gene from G. lamblia. Polymerase chain reaction(PCR) technique was used to amplify the DNA samples from the oocysts and the cysts, and those from the 6 control samples, including Schitosoma japonicum, Toxoplasma gondii , Entamoeba histolytica, Trichinella spiralis, Trichomonas vaginalis and human blood cells. DNA samples from 30 fecal samples of AIDS patients were detected with the same method.

RESULTSOne fragment of 500 bp was amplified with the primer of C. parvum, and the other one of 683 bp was amplified with the primer of G. lamblia. Twenty pg and 0.4 pg DNA of C. parvum and G. lamblia could be detected separately. The specificity of these two pairs of PCR primers was confirmed by the failure in the amplification of the control DNA samples. Out of 30 cases of AIDS patients, 7 showed C. parvum positive, while non Giardia was detected.

CONCLUSIONGenetic detection method for C. parvum and G. lamblia detection was established which was more sensitive and specific.

Acquired Immunodeficiency Syndrome ; microbiology ; Cryptosporidiosis ; diagnosis ; Cryptosporidium parvum ; genetics ; DNA, Bacterial ; Giardia lamblia ; genetics ; Giardiasis ; diagnosis ; Humans ; Polymerase Chain Reaction ; methods ; Sensitivity and Specificity

BACKGROUNDPneumocystis jirovecii pneumonia (PCP) is one of the most common and fatal infections in non-AIDS immunocompromised patients, which is difficult to diagnose by traditional morphologic methods. This study evaluated polymerase chain reaction (PCR) assays of Pneumocystis jirovecii mitochondrial large subunits ribosomal RNA in sputum and bronchioalveolar lavage fluid (BALF) for diagnosing PCP.

METHODSSputum and BALF specimens from two groups were collected: one group (PCP group) included 20 patients definitely diagnosed of PCP by Gomori methenamine silver (GMS) stains of BALF; the other group (non-PCP group) included 40 patients. Each specimen was examined by GMS stains and PCR assays.

RESULTSGMS stains of BALF in PCP group were 100% positive (20/20), GMS stains of sputum in PCP group were 35% positive (7/20); GMS stains of BALF in non-PCP group were 100% negative (40/40), GMS stains of sputum in non-PCP group were 100% negative (40/40). PCR assays of BALF in PCP group were 100% positive (20/20), PCR assays of sputum in PCP group were 100% positive (20/20); PCR assays of BALF in non-PCP group were 100% negative (40/40), PCR assays of sputum in non-PCP group were 100% negative (40/40). Sensitivity and specificity of PCR assays of sputum and BALF were both 100%; positive and negative predictive values were also both 100%.

CONCLUSIONThe diagnostic value of PCR assays of Pneumocystis jirovecii mitochondrial large subunits ribosomal RNA on sputum and BALF for pneumocystis pneumonia are both high and equivalent.

Acquired Immunodeficiency Syndrome ; diagnosis ; genetics ; Bronchoalveolar Lavage Fluid ; chemistry ; Humans ; Pneumonia, Pneumocystis ; diagnosis ; genetics ; metabolism ; Polymerase Chain Reaction ; methods ; Sputum ; chemistry

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*