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Background Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by natural killer (NK) cells plays a critical role in HIV-1 infection. As a novel subset of dendritic cells (DCs), 6-sulfo LacNAc-expressing DCs (slanDCs) also express CD16. However, the levels of slanDC-mediated ADCC during HIV-1 infection are not well addressed. Methods Forty-five HIV-1-infected subjects were enrolled and 19 HIV-1 negative individuals were used as healthy controls (HCs). The complex of gp120 and anti-gp120 was used to stimulate peripheral blood mononuclear cells (PBMCs) and the level of TNF-alpha secreted by slanDCs was detected using intercellular staining of flow cytometer. Results The counts of slanDCs in HIV-1-infected and treatment naive patients were significantly lower than those of HCs and those receiving anti-retrovirus therapy (ART) (P=0.0331, P Conclusion The slanDC-medated ADCC existed in HIV-1-infected patients and the level could be enhanced by ART, suggesting an alternative pathway involved in ADCC in HIV-1 infection. Disclosure No significant relationships.

BACKGROUND A substantial percentage (10%–15%) of HIV-infected individuals experience a sharp decline in CD4+ T-cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) vs chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. METHODS mRNA and microRNA (miRNA) expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111 (22) days [mean (SD)] of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by ROC analysis and Kaplan–Meier survival analysis. RESULTS Pathway enrichment analysis showed that genes with deregulated expression in RPs were primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, −200c, −526a, −99a, and −503) in RPs were significantly decreased compared to those in CPs (P < 0.05). The decreased expression of these miRNAs was associated with a rapid disease of progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray analysis converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. CONCLUSIONS Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection.

Context : In 2009, an outbreak of A/H1N1 influenza spread worldwide. Following the start of winter in Liaoning province in China, the number of pregnant women infected with influenza increased significantly. Some of them developed respiratory failure and multiple organ failure. Aims : The aim of this study was to determine the high-risk factors associated with the development of critical illness in the hospitalized pregnant women with A/H1N1 infection. Settings and Design : This retrospective cohort study was carried out in the tertiary care obstetric department of a large general hospital. Materials and Methods : The clinical data of H1N1 pregnant women hospitalized from November 2009 to January 2010 was reviewed. We classified these cases into severe and critical grades according to H1N1 influenza treatment guidelines. We selected maternal age, gestational age, and the time interval between symptom-onset and hospital admission as related factors of critical illness. Statistical Analysis : Logistic regression analyses to determine the relevance and importance of factors significantly associated with critical illness. Results : Eighteen cases of H1N1 influenza pregnant women were admitted. Ten pregnant women were severe cases and eight pregnant women were critical cases. The maternal age (OR=0.979, 95% CI: 0.749~1.279)and the time interval between symptom-onset and hospital admission (OR=1.41, 95% CI: 0.917~2.169) were not found to be risk factors for critical cases. The significant risk factor associated with critical illness is gestational age (OR=53.726, 95% CI: 131.165~2477.918). The risk varied by weeks of gestation, with an odds ratio of 1.034 (95% CI: 0.968-1.106) during the first trimester, 9.667 (95% CI: 0.750-124.59) during the second trimester, and 87 (95% CI: 6.750-1121.39) during the third trimester. Conclusions : Gestational age is associated with the risk of developing critical infection. The risk increases with increasing weeks of gestation.

The identification of broadly cross-reactive neutralizing (BCN) antibodies is essential for the development of a more universally effective vaccine for human immunodeficiency virus (HIV). In this study, CRF07_BC serum was analyzed for cross-clade antibody reactivity and neutralization. A total of 117 HIV-1 sera (CRF07_BC) were screened for their capacity to neutralize three primary HIV-1 isolates. A total of 18 out of 117 sera cross-neutralized all three viruses, and were tested along with eight randomly selected non-BCN sera against seven primary HIV-1 isolates and two laboratory strains that represented different clades and tropisms. BCN sera neutralized eight or all nine of these primary isolates. Non-BCN sera did not display any broadly cross-reactive neutralizing responses. BCN sera neutralized with higher frequency and geometric mean titers compared to non-BCN sera. Sera from asymptomatic individuals on average neutralized a significantly greater number of the three key isolates than sera from symptomatic individuals. Our data indicate that the three HIV-1 isolated strains are sufficient to screen broad cross-neutralizing sera, and that BCN responses may contribute to protection from infection and disease progression. The neutralizing antibody response demonstrated extensive cross-neutralization, suggesting that neutralizing antibodies induced by vaccines will have a relatively low epitope diversity to overcome in patients infected with HIV-1 B'/C recombinant (CRF07_BC).

Background Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication. Methods Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848. Results We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes. Conclusions Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.

To explore the relationship between absolute dendritic cell (DC) counts at the early stage of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) and subsequent disease progression, we performed a prospective study of 16 rapid progressors (RPs) and 12 typical progressors (TPs) from a PHI cohort of men who have sex with men. Significantly decreased plasmacytoid DC (pDC) and myeloid DC (mDC) counts in the blood of RPs were observed at study entry as compared with TPs and healthy HIV-1-negative subjects. Low baseline pDC counts were significantly associated with rapid disease progression after adjustment for baseline CD4(+) T cell counts, mDC counts, and HIV-1 load. Kaplan-Meier survival analysis showed that low pDC counts were strongly associated with rapid disease progression. Our findings demonstrated the predictive value of blood absolute pDC counts at baseline in PHI for HIV-1 disease progression. Further studies are required to confirm this notion.

Objective: To explore correlations between mRNA (hA3G, hA3F, and hA3B) levels and CD4 + T-cell counts and HIV-1 viral loads to evaluate their respective roles in disease progression. Methods: Real-time polymerase chain reaction was used to quantify the mRNA levels of hA3G, hA3B, and hA3F in peripheral blood mononuclear cells from slow progress patients (SP), asymptomatic HIV-infected patients (AS), AIDS patients, and HIV-negative controls. Results: The levels of hA3G and hA3B mRNA correlated positively with CD4 + T-cell counts (r = 0.436, P = 0.002, r = 0.334, P = 0.025), and negatively with HIV-1 viral loads (r = -0.306, P = 0.038, r = -0.301 P = 0.044). The levels of hA3G and hA3B mRNA in HIV-infected subjects were lower than in HIV-negative controls (P < 0.05), and hA3G and hA3B mRNA levels were significantly higher in SP than in AIDS patients (P < 0.05). There was no correlation between the hA3F mRNA level and CD4 + T-cell counts or between the hA3F mRNA level and HIV-1 viral loads. Conclusions: Higher expression levels of hA3G and hA3B mRNA in the peripheral blood mononuclear cells of Chinese HIV-infected individuals were found to be associated with slower HIV disease progression, suggesting their potential roles in antiviral innate immunity.

To determine the relative resistance to HIV-1 infection of CD4 + T lymphocytes in HIV-exposed seronegative individuals (ESNs) in China.HIV primary isolates were obtained from peripheral whole blood of HIV-infected persons. CD4 + T lymphocytes of Chinese ESNs were separated from peripheral blood mononuclear cells with magnetic cell sorting (MACS). The purified CD4 + T lymphocytes were cocultured with HIV primary isolates. The p24 level was detected and the culture medium was refreshed every 3 days within 2 weeks.For M tropic HIV strains, p24 level was significantly lower in ESN group than in control group (P0.05); for some M tropic HIV strains, even no p24 replicated in ESN group. However, T tropic virus strains had no significant difference between these two groups (P0.05).CD4 + T lymphocytes of Chinese ESNs may possess relative resistance to M tropic HIV strains, which may be one of the main influencing factors that result in ESN.