[Show abstract][Hide abstract] ABSTRACT: During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined.
EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients.
When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression.
During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.
[Show abstract][Hide abstract] ABSTRACT: Importance:
Current antiretroviral therapy is very effective in suppressing active HIV-1 replication, but does not fully eliminate virally infected cells. The ability of HIV-1 to persist long-term despite suppressive antiretroviral combination therapy represents a perplexing aspect of HIV-1 disease pathogenesis, since most HIV-1 target cells are activated, short-lived CD4 T cells. This study suggests that CD4 T helper cells with Th1/Th17 polarization have a preferential role as a long-term reservoir for HIV-1 infection during antiretroviral therapy, possibly because these cells may imitate some of the functional properties traditionally ascribed to stem cells, such as the ability to persist for extremely long periods of time and to repopulate their own pool size through homeostatic self-renewal. These observations support the hypothesis that HIV-1 persistence is driven by small subsets of long-lasting stem cell-like CD4 T cells that may represent particularly promising targets for clinical strategies aiming at HIV-1 eradication and cure.
Journal of Virology 09/2015; DOI:10.1128/JVI.01595-15 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between the cognitive impairment and hippocampal morphological and functional change in HIV-seropositive patients.
30 HIV+ patients who complain of memory-decreasing and 15 healthy volunteers were recruited. Performances of learning and memory were assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). Bilateral hippocampal volume, ADC value, FA value and MR spectroscopy variables of bilateral hippocampus and parahippocampus gyrus was detected by 3.0 T MR scanner.
We found significant differences in the all cognitive outcomes but one between HIV+ and HIV-. There was a difference in the ADC value of left parahippocampus gyrus between mild-impairment group and severe-impairment group (p=0.018). We found differences in the Cho, Cho/Cr, NAA/Cr of left hippocampus (p=0.002; p=0.008; p=0.002) and the Cho/Cr of right parahippocampus gyrus (p=0.023) between HIV+ and HIV-, and in the MI of left hippocampus (p=0.003) and the Glx of right hippocampus (p<0.001) between mild-impairment group and severe-impairment group. We found significantly positive correlations between NAA/Cr of left hippocampus and outcomes of HVLT-R, BVMT-R. There were significantly negative correlations between ADC value of hippocampus, parahippocampus gyrus and outcomes of HVLT-R, BVMT-R, and between Cho, Cho/Cr of hippocampus, parahippocampus gyrus and outcomes of HVLT-R, BVMT-R.
The performance of verbal learning and visual memory was significantly decreased in HIV-1 seropositive patients. The cognitive impairment of HIV infection was associated with conductive function and metabolic changes of hippocampus and parahippocampus gyrus in this study.
[Show abstract][Hide abstract] ABSTRACT: Background
Recent upsurge of new HIV infections among men who have sex with men (MSM) is a major concern in China. Paucity of national-level information regarding the burden and predictors of this progressive epidemic of new infections called for a multi-centric, comprehensive investigation to determine incidence and prevalence of HIV infections (both early and established) and their predictors.
Methods and findings
In a multi-center cross-sectional study with a prospective component, 4496 eligible, consenting (written) MSM were recruited (non-response=0.22%), interviewed and undergone tests for HIV (Wesern blot(WB) and BED HIV-1 capture enzyme immunoassay IgG captured EIA(BED-CEIA) were jointly used to determinealong with HIV early(recent) or/and established case differentiationinfection), syphilis and herpes simplex virus-2 (HSV-2), in seven cities of China (Shanghai, Nanjing, Changsha, Zhengzhou, Ji’nan, Shenyang and Kunming) between June 2012 and June 2013.
Majority participants were aged ≤35 years (77.52%), migrants (60.27%), never married (69.79%), receptive during anal sex (70.52%) %) and found partners mainly through internet (67.94%). Only 8.47% got circumcised, 27.85% did not use condom during last anal sex, 28.32% used recreational drugs and 15.46% reported anal bleeding post intercourse.
HIV prevalence was 9.9% ( [95% Confidence Intervals (CI) =4.0 %-13.913.9 %] %). Among HIV cases 41.89% were recently infected, with HIVand incidence was of 8.90/100 Person-Years (95%CI =7.62-10.17). Among HIV cases 41.89% were recently infected. Prevalence for HSV-2 and syphilis were 11.9512.50% and 8.47%, respectively. Among HIV cases 41.89% were recently infected.
Compared to respective reference groups, higher odds of recent acquisition of HIV was associated with sexual debut during 16-25 years (aOR=3.20, 95%CI =1.01-10.22), playing receptive role (aOR=2.62, 95%CI =1.38-3.08), having multiple male partners (aOR=1.54, 95%CI =1.12-2.13), recreational drug use (aOR=1.98, 95%CI =1.39-2.80), anal bleeding (aOR=1.73, 95%CI =1.14-2.60) and having syphilis (aOR=3.08, 95%CI =2.04-4.67) or HSV-2 (aOR=2.43, 95%CI =1.58-3.73).
High rate of early HIV infection is potentially resulting in progressive deterioration of the overall HIV situation epidemic among MSM in China. Targeted interventions to address high-risk MSM including those having later sexual debut, receptive role, multiple partners, history of recreational drug use, syphilis or HSV-2 infection and anal bleeding seemed to be the need of the hour.
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies (GWASs) have revealed several genetic loci associated with HIV-1 outcome following infection (e.g., HLA-C at 6p21.33) in multi-ethnic populations with genetic heterogeneity and racial/ethnic differences among Caucasians, African-Americans, and Hispanics. To systematically investigate the inherited predisposition to modulate HIV-1 infection in Chinese populations, we performed GWASs in three ethnically diverse HIV-infected patients groups (i.e., HAN, YUN, and XIN, N = 538). The reported loci at 6p21.33 was validated in HAN (e.g., rs9264942, P = 0.0018). An independent association signal (rs2442719, P = 7.85 × 10(-7), HAN group) in the same region was observed. Imputation results suggest that haplotype HLA-B*13:02/C*06:02, which can partially account for the GWAS signal, is associated with lower viral load in Han Chinese. Moreover, several novel loci were identified using GWAS approach including the top association signals at 6q13 (KCNQ5, rs947612, P = 2.15 × 10(-6)), 6p24.1 (PHACTR1, rs202072, P = 3.8 × 10(-6)), and 11q12.3 (SCGB1D4, rs11231017, P = 7.39 × 10(-7)) in HAN, YUN, and XIN groups, respectively. Our findings imply shared or specific mechanisms for host control of HIV-1 in ethnically diverse Chinese populations, which may shed new light on individualized HIV/AIDS therapy in China.
[Show abstract][Hide abstract] ABSTRACT: The data from apparently healthy individuals with thalassemia has been demonstrated to have an effect on the reference intervals for the erythrocyte indices in areas with a high incidence of thalassemia.
Six clinical centers screened apparently healthy individuals using a questionnaire and a physical examination. Then, the qualified reference individuals were selected by hematological indices and a genotypic thalassemia diagnosis. Statistical comparisons were conducted for the erythrocyte reference intervals in the Chinese population with and without thalassemia. The constituent ratios and the mean (SD) of erythrocyte indices according to the thalassemia genotype were calculated. The relationship between the MCV values and the thalassemia genotype was also estimated.
4,636 reference individuals were included using hematological indices and genotypic thalassemia screening. The results of the erythrocyte reference intervals for individuals in Guangzhou with thalassemia demonstrated that the RBC, MCV, and MCH values significantly differed by gender compared with other regions (p < 0.01). In contrast, for individuals without thalassemia, the results tended to be similar and clinically acceptable. In addition, the results of the erythrocyte indices revealed significant differences among α-thalassemia patients, β-thalassemia patients, and the control group.
Apparently healthy individuals with thalassemia in the high prevalence zone of thalassemia could not be excluded by the questionnaire, physical examination or laboratory indices (Fe < 6 μmol/L, Hb < 90 g/L). The screening of genotypic thalassemia based on the MCV or MCH values to exclude unqualified individuals is the most effective way to obtain accurate and reliable reference intervals for the erythrocyte indices.
[Show abstract][Hide abstract] ABSTRACT: The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latent nuclear antigen LANA plays an essential role in viral episome maintenance. LANA also contributes to DNA replication and tumorigenesis during latency. Recent studies suggested that LANA was involved in regulation of SUMOylation which results in chromatin silencing. To examine the pleiotropic effects of LANA protein on host cell gene expression, we utilized MS analysis to identify cellular proteins associated with the SUMO-Interacting Motif of LANA (LANA(SIM) ). In addition to the 6 bands identified as substantially associated with LANA(SIM) , 151 proteins were positively identified by MS/MS analysis. Compared with previous proteomic analysis of the N- and C- truncated mutants of LANA (LANA(NC) ), our results revealed that a complex of specific proteins with relatively high SUMOylation and SIM motifs are associated with LANA(SIM) . Intriguingly, consistent with our previous report that identified KAP1 as a key component, the in-vitro SUMO-2 modified isoform has a substantially higher affinity with LANA(SIM) than the SUMO-1 modified isoform. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the LANA(SIM) regulatory circuit involving aberrant SUMOylation of cell cycle (particular mitotic), DNA unwinding and replication, and pre-mRNA/mRNA processing-related proteins. This study provides a SUMOylated and non-SUMOylated proteome profile of LANA(SIM) -associated complex, and facilitates our understanding that viral-mediated gene regulation through SUMOylation is important for KSHV persistence and pathogenesis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Co-signaling molecules have been demonstrated to regulate regulatory T cells' (Tregs) function during human immunodeficiency virus (HIV) infection. A recently reported co-signaling molecule called herpes virus entry mediator (HVEM), a member of the tumor necrosis factor receptor family, can both enhance and inhibit the immune response. HVEM was also reported to enhance the suppressive function of regulatory T cells in mice. However, it remains unknown whether HVEM can regulate Treg function in HIV-infected patients or whether HVEM affects HIV disease progression. In this study, we found that the blockage of the HVEM could weaken Tregs' suppressive activity to effector T cells (Teffs). HVEM expression is reduced during the asymptomatic phase of HIV infection and fairly predictive of the recovery of CD4+T-cells in response to highly active anti-retroviral therapy (HAART), more so than nadir CD4+T-cell count or viral load. Taken together, these findings demonstrate the importance of HVEM in relation to Treg function and HIV disease progression, which would have therapeutic implications and provide insight into the pathogenesis of acquired immune deficiency syndrome (AIDS).
Current HIV research 04/2015; 13(2):151-9. DOI:10.2174/1570162X1302150415110714 · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The expression of ATP-dependent efflux pump P-glycoprotein (P-gp) in cancer cells generally results in multidrug resistance (MDR) to chemotherapeutic drugs, which is the main cause of chemotherapy failure in cancer treatment. The intracellular drug levels could be increased by some MDR reversal agents that inhibited the drug efflux activity of P-gp. The synthesized DNA nucleic acids of G-quadruplex represent a novel and unique class of anti-cancer agents. While there was no report on the roles of DNA G-quadruplex oligonucleotides (GQ-ODNs) in the MDR reversal, the present study was performed to investigate the ability of synthesized GQ-ODNs to reverse P-gp-mediated MDR and its mechanism in paclitaxel (PTX)-resistant SKOV3 (SKOV3/PTX) cells and their sensitive cell lines SKOV3. The ability of GQ-ODNs to reverse drug resistance was evaluated by MTS assay. The results showed that GQ-ODNs can reverse PTX resistance effectively. The potential of GQ-ODNs as reversal agents was evaluated with the nude mice tumor xenograft model and showed that the co-administration of the GQ-ODNs and PTX had better effects and was also more evident than treatment with only PTX. The P-gp expression was assessed by the Western blot; it showed that SKOV3/PTX cells showed highly expressed P-gp protein, while their sensitive cells scarcely showed P-gp. The presence of GQ-ODNs efficiently decreased the P-gp expression, showing that GQ-ODNs could reverse P-gp-mediated MDR by decreasing the expression of P-gp. This study indicated that GQ-ODNs could effectively reverse P-gp-mediated PTX resistance by inhibiting the expression of P-gp and by the co-administration of GQ-ODNs and PTX that could increase the apoptosis of SKOV3/PTX cells. Thus, the synthesized GQ-ODNs may be a potential inhibitor to overcome drug resistance.
[Show abstract][Hide abstract] ABSTRACT: Complete blood count (CBC) reference intervals are important to diagnose diseases, screen blood donors, and assess overall health. However, current reference intervals established by older instruments and technologies and those from American and European populations are not suitable for Chinese samples due to ethnic, dietary, and lifestyle differences. The aim of this multicenter collaborative study was to establish CBC reference intervals for healthy Han Chinese adults.
A total of 4,642 healthy individuals (2,136 males and 2,506 females) were recruited from six clinical centers in China (Shenyang, Beijing, Shanghai, Guangzhou, Chengdu, and Xi'an). Blood samples collected in K2EDTA anticoagulant tubes were analyzed. Analysis of variance was performed to determine differences in consensus intervals according to the use of data from the combined sample and selected samples.
Median and mean platelet counts from the Chengdu center were significantly lower than those from other centers. Red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) values were higher in males than in females at all ages. Other CBC parameters showed no significant instrument-, region-, age-, or sex-dependent difference. Thalassemia carriers were found to affect the lower or upper limit of different RBC profiles.
We were able to establish consensus intervals for CBC parameters in healthy Han Chinese adults. RBC, HGB, and HCT intervals were established for each sex. The reference interval for platelets for the Chengdu center should be established independently.
PLoS ONE 03/2015; 10(3):e0119669. DOI:10.1371/journal.pone.0119669 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The HLA-A*30-B*13-C*06 haplotype is reported to be associated with slow disease progression in HIV-1-infected Northern Han Chinese, but the mechanism remains unknown.
Gag-specific T cell responses and gag sequencing were performed in nine B' clade HIV-1-infected HLA-A*30-B*13-C*06-positive slow progressors to understand HLA associated viral control.
IFN-γ ELISPOT assays were performed to determine the Gag-specific T cell responses and cross reactivity to variants peptides. Longitudinal HIV-1 gag sequencing was performed at clonal level.
The overlapping peptides (OLP)-48: RQANFLGKIWPSHKGRPGNF (RL42 Gag434-453); OLP-2: GQLDRWEKIRLRPGGKKKYR (RL42 Gag11-30); OLP-15: VQNLQGQMVHQPISPRTLNA (RL42 Gag135-154) and OLP-16: HQPISPRTLNAWVKVVEEKA (RL42 Gag144-163) were dominant in HLA-A*30-B*13-C*06-positive patients. A new epitope (HQPISPRTL (Gag144-152, HL9)) within OLP-15 and OLP-16 was identified. Results showed that strong cross reactive responses to multiple immunodominant peptides were associated with better clinical outcomes. In addition, efficient cross-recognition of HL9 autologous variants developed in patients was associated with high CD4 T-cell counts. However, two patients who had developed mutations to their dominant responses during the follow up experienced decrease in CD4 T-cell counts. It appears that Gag-specific T cell responses against one or more un-mutated epitopes or cross-recognition of autologous epitope variants contribute to slow disease progression in HLA-A*30-B*13-C*06-positive patients.
We conclude that a single "appropriate" Gag-specific T cell response appears to be sufficient to protect patients from disease progression. HLA-A*30-B*13-C*06-positive individuals benefited from having a choice of numerous immunodominant gag epitopes for T cells to react. The study offers new insight for future design of T cell based HIV-1 vaccine.
AIDS (London, England) 03/2015; 29(9). DOI:10.1097/QAD.0000000000000652 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To explore the association between differential Tim-3 and PD-1 expression patterns and HIV disease progression, and to investigate the impact of common γ-chain cytokines on Tim-3 and PD-1 expression patterns on T cells.
Tim-3/PD-1 expression on the T cells of patients with early and chronic HIV infections was detected. The expression levels and functional profiles of T cells with differential Tim-3 and PD-1 expression patterns induced by γ-chain cytokines were studied.
The elevation of differential Tim-3 and PD-1 expression patterns on T cells appeared early in HIV infection. Co-expression of Tim-3 and PD-1 (Tim-3+PD-1+) correlates with more severe exhaustion of T cells during HIV infection. In vitro stimulation of common γ-chain cytokines can induce differential expression patterns of Tim-3 and PD-1 on T cells. The enhancement of Tim-3 and PD-1 expression by common γ-chain IL-2 can inhibit the function of T cells re-stimulated by HIV gag and TCR, not by the re-stimulation of IL-2.
The elevation of differential Tim-3 and PD-1 expression patterns on T cells represents a state of T cell exhaustion and can be induced by common γ-chain cytokines. These findings provide insights into HIV pathogenesis and help inform immune intervention strategies.
[Show abstract][Hide abstract] ABSTRACT: To determine sensitivity of rapid diagnostic tests for detecting influenza A(H7N9) virus, we compared rapid tests with PCR results and tested different types of clinical samples. Usefulness of seasonal influenza rapid tests for A(H7N9) virus infections is limited because of their low sensitivity for detecting virus in upper respiratory tract specimens.
[Show abstract][Hide abstract] ABSTRACT: Background
Sexually transmitted infections (STIs) increase HIV infectivity through local inflammatory processes. Prevalent and incident STIs among people who live with HIV/AIDS (PLWHA) are indicators of high-risk sexual behaviors and imply potential spread of HIV. Little is known about the prevalence and incidence of concurrent syphilis and associated risk behaviors among PLWHA in China.MethodsA retrospective cohort study was conducted among PLWHA who attended the outpatient clinic of a designated AIDS treatment hospital in Shenyang, China, between March 2009 and May 2013. Physical examinations and syphilis serology were conducted at each visit. A questionnaire on demographic characteristics was also collected.ResultsA total of 1010 PLWHA were enrolled, of whom 77.0% were men who have sex with men (MSM). The baseline syphilis prevalence among PLWHA was 19.8% (95% confidence interval [CI]:17.3¿22.3%). During follow-up, 78.3% retained in the cohort, and contributed a median follow-up of 9.4 months (interquartile range: 5.9-18.7 months). Syphilis incidence among PLWHA was 18.7 (95% CI: 15.5¿21.8) per 100 person years. Mulitvariate logistic analysis showed that receiving antiretroviral therapy (ART) (adjusted OR [aOR]¿=¿0.48), older age (¿40 years vs. ¿24 years, aOR¿=¿2.43), being MSM (aOR¿=¿2.30) and having higher baseline HIV viral load (>100000 copies/mL vs. ¿100000 copies/mL, aOR¿=¿1.56) were independent predictors for syphilis infection among PLWHA at enrollment (p¿<¿0.05 for all). Mulivariate Cox regression found that receiving ART (adjusted hazard ratio [aHR]¿=¿1.81), older age (¿40 years vs. ¿24 years, aHR: 5.17) and MSM status (aHR¿=¿2.68) were independent risk factors for syphilis seroconversion (each p¿<¿0.05).Conclusions
Syphilis prevalence and incidence were high among PLWHA in Shenyang. A campaign focusing on detection and treatment of syphilis among PLWHA is urgently needed, especially one with a focus on MSM who are at a higher risk for syphilis.