Molecular epidemiological characteristics of newly diagnosed HIV-1 cases in Fujian Province in 2020 / 中国血吸虫病防治杂志

Objective To investigate the HIV-1 genotype and distribution of newly diagnosed HIV-1 cases in Fujian Province in 2020, so as to provide insights into formulation of the precise AIDS control strategy in the province. Methods Newly diagnosed HIV-1 cases without antiretroviral therapy (excluding AIDS patients) were randomly sampled from each city of Fujian Province in 2020 at a proportion of 50% of the mean number of HIV-infected cases reported across 9 cities of Fujian Province during the past three years. Subjects’ demographic and epidemiological data were collected and blood samples were collected. The HIV-1 pol gene was amplified using nested reverse-transcription PCR assay, and the gene sequences were used for HIV-1 genotyping and phylogenetic analysis. The gene sequences were uploaded to the HIV Drug Resistance Database (http://hivdb.stanford.edu) for genotypic drug resistance assays, and the scores and level of HIV drug resistance were estimated using the HIVDB Algorithm version 9.5. Results A total of 1 043 newly diagnosed HIV-1 cases were reported in Fujian Province in 2020, and 936 gene sequences were successfully obtained following sequencing of blood samples. There were 9 HIV-1 genotypes characterized in blood samples from 936 newly diagnosed HIV-1 cases, with CRF07_BC (52.1%) and CRF01_AE (30.4%) as predominant subtypes, followed by CRF08_BC (4.9%), CRF55_01B (3.0%), subtype C (2.5%), subtype B (2.1%), CRF85_BC (1.7%), CRF59_01B (0.3%) and CRF65_CPX (0.1%), and unidentified subtypes were found in 26 blood samples. HIV-1 drug resistance was detected in 43 out of the 936 newly diagnosed HIV-1 cases, with 4.6% prevalence of HIV-1 drug resistance prior to therapy, and the highest drug resistance was found in the HIV CRF59_01B subtype, followed by in CRF08_BC, B, C, CRF01_AE, CRF07_BC and other subtypes, with a significant difference in the genotype-specific prevalence of HIV-1 drug resistance (χ2 = 45.002, P < 0.05). Conclusions There was a HIV-1 genotype diversity in Fujian Province in 2020, and emerging recombinant and drug-resistant HIV-1 strains were detected and spread across patients and regions. Monitoring of HIV-1 genotypes is recommended to be reinforced for timely understanding of the transmission and spread of novel recombinant and drug-resistant HIV-1 strains.

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication / 中华医学杂志(英文版)

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.

Modular analysis of target genes of microRNAs in plasma of coal-burning fluoride exposed population based on protein-protein interaction network / 中华地方病学杂志

Objective:To establish a protein-protein interaction (PPI) network of 5 microRNA (miRNA) target genes differentially expressed in the plasma of coal-burning fluoride exposed population, and to screen genes and gene modules with important roles.Methods:Five miRNA (hsa-miRNA-3131, hsa-miRNA-4516, hsa-miRNA-6501-5p, hsa-miRNA-10b-5p, hsa-miRNA-4683) target genes differentially expressed in the plasma of coal-burning fluoride exposed population screened by our previous study were mapped to the STRING online database (https://string-db.org), and the PPI network was screened. The Cytoscape v3.6.0 software was used to visualize the PPI network, the topological attribute values degree and betweenness centrality were obtained by the NetworkAnalyzer plug-in, and the central node was filtered in the network (the node with the highest degree and the highest betweenness centrality). At the same time, the maximal clique centrality (MCC) analysis method in the CytoHubba plug-in was used to determine the important nodes in the PPI network. The cluster analysis was conducted by the MCODE plug-in, and the gene modules were screened in the PPI network. The protein names contained in the gene modules were submitted online to the KOBAS v3.0 database (http://kobas.cbi.pku.edu.cn/), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the gene modules selected by the MCODE plug-in.Results:The PPI network of target genes was consisted of 1 035 nodes and 4 346 edges. The degree (101) and betweenness centrality (0.010 723 89) of ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) were the highest, which was the central node of the PPI network. According to MCC analysis, UBA52 was an important node in the PPI network. The top 5 gene modules were selected from the PPI network, and the highly enriched gene pathways in the KEGG pathway enrichment analysis of the 5 gene modules included ubiquitin mediated proteolysis, spliceosome, endocytosis, neuroactive ligand-receptor interaction and vesicular transport.Conclusion:The PPI network of 5 miRNA target genes differentially expressed in the plasma of people exposed to coal-burning pollution of fluoride is successfully established, and the UBA52 gene and the 5 main pathways of gene modules are selected.

Analysis on influencing factors that leading to nonspecific responses to indeterminate results of HIV antibodies / 中华流行病学杂志

Objective To identify the influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests,to provide scientific evidence for the differential diagnosis of HIV infection and control strategy.Methods A case control study was conducted.The samples of HIV antibody indeterminate in confirmed Western blot (WB) tests,but were negative in HIV nucleic acid tests,were collected as HIV antibody indeterminate group from WB results of HIV confirmatory laboratories of Fujian province in 2015-2016.The general population matched group with HIV antibody screening negative samples and WB negative matched group with WB negative samples were selected as the two compared groups by matching gender and age from HIV antibody screening in Fujian province in the same period.Blood concentrations of hepatitis B surface antigen (HBsAg),anti-hepatitis C virus (HCV) antibody,anti-treponema pallidum (TP) antibody,antinuclear antibody (ANA),anti-human T-cell leukemia virus (HTLV) antibody,and alpha-fetoprotein (AFP) were detected by using enzyme-linked immunosorbent assay (ELISA).x 2 test and multivariate non-conditional logistic regression analysis were performed to identify the influencing factors that leading to nonspecific responses,to indeterminate HIV antibody tests.Results A total of 13 WB baud patterns were observed in 110 HIV antibody indeterminate samples,in which a single p24 band (58.18％,64/110),a single gp160 band (17.27％,19/110) and a single p 17 band (7.27％,8/110) were the three most common patterns.The positive rate of anti-TP antibody was significantly higher in HIV antibody indeterminate samples than general population control group and WB negative control group (10.91％,12/110 vs.1.77％,4/226 and 3.64％,4/110),compared with two control groups (x2=13.627 and 4.314,P＜0.05).The positive rate of AFP was significantly higher in HIV antibody indeterminate samples than general population control group (18.18％,20/110 vs.0.44％,1/226,x2=39.736,P＜0.05),the different was not significant compared with WB negative control group (18.18％,20/110 vs.23.64％,26/110,x2=0.990,P＞0.05) While no significant differences were found between HIV antibody indeterminate group and two control groups in terms of the positive rates of ANA,HBsAg,anti-HCV antibody or anti-HTLV antibody.Conclusions The influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests appeared complicate,and the anti-TP antibody positivity might be an influencing factor responsible for nonspecific responses to indeterminate HIV antibody tests.

Analysis on influencing factors that leading to nonspecific responses to indeterminate results of HIV antibodies / 中华流行病学杂志

Objective To identify the influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests,to provide scientific evidence for the differential diagnosis of HIV infection and control strategy.Methods A case control study was conducted.The samples of HIV antibody indeterminate in confirmed Western blot (WB) tests,but were negative in HIV nucleic acid tests,were collected as HIV antibody indeterminate group from WB results of HIV confirmatory laboratories of Fujian province in 2015-2016.The general population matched group with HIV antibody screening negative samples and WB negative matched group with WB negative samples were selected as the two compared groups by matching gender and age from HIV antibody screening in Fujian province in the same period.Blood concentrations of hepatitis B surface antigen (HBsAg),anti-hepatitis C virus (HCV) antibody,anti-treponema pallidum (TP) antibody,antinuclear antibody (ANA),anti-human T-cell leukemia virus (HTLV) antibody,and alpha-fetoprotein (AFP) were detected by using enzyme-linked immunosorbent assay (ELISA).x 2 test and multivariate non-conditional logistic regression analysis were performed to identify the influencing factors that leading to nonspecific responses,to indeterminate HIV antibody tests.Results A total of 13 WB baud patterns were observed in 110 HIV antibody indeterminate samples,in which a single p24 band (58.18％,64/110),a single gp160 band (17.27％,19/110) and a single p 17 band (7.27％,8/110) were the three most common patterns.The positive rate of anti-TP antibody was significantly higher in HIV antibody indeterminate samples than general population control group and WB negative control group (10.91％,12/110 vs.1.77％,4/226 and 3.64％,4/110),compared with two control groups (x2=13.627 and 4.314,P＜0.05).The positive rate of AFP was significantly higher in HIV antibody indeterminate samples than general population control group (18.18％,20/110 vs.0.44％,1/226,x2=39.736,P＜0.05),the different was not significant compared with WB negative control group (18.18％,20/110 vs.23.64％,26/110,x2=0.990,P＞0.05) While no significant differences were found between HIV antibody indeterminate group and two control groups in terms of the positive rates of ANA,HBsAg,anti-HCV antibody or anti-HTLV antibody.Conclusions The influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests appeared complicate,and the anti-TP antibody positivity might be an influencing factor responsible for nonspecific responses to indeterminate HIV antibody tests.

Research progress of AIDS treatment / 中国人兽共患病学报

AIDS antiviral therapy (ART) has achieved great success.Originaly,AIDS had been regarded as a fatal disease,but it has become a kind of infectious disease that could be cured and administrated.Global HIV / AIDS cases were still up to about 38 million,but more than half have been effectively treated.In addition to drug treatment,at present,some new technologies and new methods,such as genome editing,have also been involved in the treatment of AIDS,and in the humanized animal experiment has shown very good results.There is no doubt that AIDS will eventually be stopped its epidemic.However,with the continuous development of AIDS antiviral treatment,the most fundamental problem is that HIV latent library has become increasingly prominent one,whether molecular therapy and hybrid cure have being developed for AIDS treatment,there are still such problem existence.Great efforts shoud be made to continuously search for new markers of latent viral cells and to reduce the latent pool.In addition,despite the prevention and treatment of AIDS has made great achievements,but the world still produces nearly 6000 cases of HIV/AIDS every day.Therefore,the development of safe and effective vaccine,whether in the field of prevention,or in clinical treatment,has its positive significance.

Epidemiological investigation and follow-up study of different populations with indeterminate results of HIV antibody test in Fujian / 中华微生物学和免疫学杂志

Objective To investigate the ratios and the distribution of subjects with indeterminate results of HIV antibody in different populations who were positive for HIV screening test in Fujian and to ana-lyze the features of Western blot bands for further understanding the relationships between the Western blot band patterns and HIV infection. Methods The subjects who were diagnosed with indeterminate results of HIV antibody at the first examination were re-tested with Western blot assay every month until the results turned into HIV antibody-positive or HIV antibody-negative. Results The detection rate of indeterminate results of HIV antibody was 3. 69% in Fujian in 2015. Higher rates were detected in blood donors, pregnant woman and other clinical patients. The most common band patterns of HIV antibody-indeterminate samples were p24, gp160+p24 and gp160. Results of the follow-up confirmatory tests showed that 76% of the sam-ples of p24 band pattern were HIV antibody-negative and 76. 47% of the samples of gp160+p24 band pattern were HIV antibody-positive. The nucleic acid test showed that positive results were detected in 29 samples whose band patterns were gp160+gp120+p24,gp160+gp120+p66andgp160+gp120+p31. Conclusion The detection rates of indeterminate results of HIV antibody varied in different populations. The most com-mon band patterns of HIV antibody-indeterminate samples were p24, gp160+p24 and gp160. The more bands the samples presented themselves in Western blot assay, the more likely they would be HIV antibody-positive. Follow-up should be strengthened to prevent the spread of HIV infection. Samples with the band pattern of gp160+gp120+p24 showed a low probability of false positive and they were more likely to be end-stage AIDS with immunosuppression.

Genetic subtype and epidemiological feature of HIV-1 circulating strains among recently infected patients in Fujian province / 中华流行病学杂志

Objective In order to evaluate the distribution of genetic subtypes and epidemiological feature of HIV-1 circulating strains in Fujian province. Methods Blood samples and epidemiological data were collected from 104 newly infected patients who were distinguished by BED-CEIA methodology,during 2011-2012. Viral sequences (n=81) of HIV-1 gag,env,and pol segments were amplified by nested PCR. Results Subtypes B and four Circulating Recombinant Forms,(CRF01_AE,CRF07_BC,CRF08_BC and CRF55_01B) were found in the samples, CRF01_AE(45.68%)and CRF07_BC(35.80%)were the two main HIV-1 strains in Fujian province. Compared with previous data,the proportion of CRF07_BC rose significantly while it gradually decreased in CRF01_AE. Heterosexual contact was still the principal transmission route in Fujian province, but the number of infection among men-who-have-sex-with- men grew rapidly. Conclusion Results from this study suggested that different subtypes of HIV-1 strain existed in Fujian province. The distribution of subtypes and the mode of transmission were changing with the progress of epidemic. Dynamic monitoring of the molecular epidemiology trends of HIV-1 infection should be enhanced.

Genetic subtype and epidemiological feature of HIV-1 circulating strains among recently infected patients in Fujian province / 中华流行病学杂志

Objective In order to evaluate the distribution of genetic subtypes and epidemiological feature of HIV-1 circulating strains in Fujian province. Methods Blood samples and epidemiological data were collected from 104 newly infected patients who were distinguished by BED-CEIA methodology,during 2011-2012. Viral sequences (n=81) of HIV-1 gag,env,and pol segments were amplified by nested PCR. Results Subtypes B and four Circulating Recombinant Forms,(CRF01_AE,CRF07_BC,CRF08_BC and CRF55_01B) were found in the samples, CRF01_AE(45.68%)and CRF07_BC(35.80%)were the two main HIV-1 strains in Fujian province. Compared with previous data,the proportion of CRF07_BC rose significantly while it gradually decreased in CRF01_AE. Heterosexual contact was still the principal transmission route in Fujian province, but the number of infection among men-who-have-sex-with- men grew rapidly. Conclusion Results from this study suggested that different subtypes of HIV-1 strain existed in Fujian province. The distribution of subtypes and the mode of transmission were changing with the progress of epidemic. Dynamic monitoring of the molecular epidemiology trends of HIV-1 infection should be enhanced.

Genetic subtype and epidemiological feature of HIV-1 circulating strains among recently infected patients in Fujian province / 中华流行病学杂志

<p><b>OBJECTIVE</b>In order to evaluate the distribution of genetic subtypes and epidemiological feature of HIV-1 circulating strains in Fujian province.</p><p><b>METHODS</b>Blood samples and epidemiological data were collected from 104 newly infected patients who were distinguished by BED-CEIA methodology, during 2011-2012. Viral sequences(n = 81) of HIV-1 gag, env, and pol segments were amplified by nested PCR.</p><p><b>RESULTS</b>Subtypes B and four Circulating Recombinant Forms, (CRF01_AE, CRF07_BC, CRF08_BC and CRF55_01B) were found in the samples, CRF01_AE(45.68%)and CRF07_BC(35.80%) were the two main HIV-1 strains in Fujian province. Compared with previous data, the proportion of CRF07_BC rose significantly while it gradually decreased in CRF01_AE. Heterosexual contact was still the principal transmission route in Fujian province, but the number of infection among men-who-have-sex-with- men grew rapidly.</p><p><b>CONCLUSION</b>Results from this study suggested that different subtypes of HIV-1 strain existed in Fujian province. The distribution of subtypes and the mode of transmission were changing with the progress of epidemic. Dynamic monitoring of the molecular epidemiology trends of HIV-1 infection should be enhanced.</p>

Application of heteroduplex mobility assay in genetic subtyping on human immunodeficiency virus type 1 / 中华流行病学杂志

<p><b>OBJECTIVE</b>Using heteroduplex mobility assay (HMA) to subtype human immunodeficiency virus type 1 (HIV-1) for the purpose of understanding HIV-1 subtype epidemic in Fujian province.</p><p><b>METHODS</b>DNA fragments of HIV-1 env gene were amplified from peripheral blood mononuclear cell (PBMC) cocultures of HIV-1 infected individuals by nested polymerase chain reaction (PCR). Heteroduplexs were formed through hybridizing PCR products from the samples and reference plasmid. According to the mobility of heteroduplexs in polyacrylamide gel electrophoresis, HIV-1 subtype from that sample was characterized and further confirmed by nucleotide sequencing analysis.</p><p><b>RESULTS</b>Thirteen of 15 (86.67%) samples were successfully subtyped by HMA, except 2 failures. Subtype E and B took up 80% (12/15) and 6.67% (1/15) respectively. Results indicated a high concordance between HMA and nucleotide sequencing analysis and concordance rate was 86.67% (13/15).</p><p><b>CONCLUSIONS</b>Subtype E appeared to be the major epidemic strain of HIV-1 in Fujian. HMA showed the characteristics of fastness, easiness, economic and with high specificity, and can be used in the surviellance for the epidemic strain of HIV-1.</p>