Role of GBV-C and human herpes virus coinfections in AIDS development in HIV-1 seroconverters

Background: GB virus type C (GBV-C) co-infection prolongs survival among Human Immunodeficiency Virus (HIV) infected individuals. Chronic immune activation is associated with HIV-1 disease progression. Objective: To investigate the effect of GBV-C coinfection and herpes virus reactivation on AIDS development in HIV-1 seroconverters. Methods: A total of 272 men HIV-1 seroconverters were included for the analysis. Cox proportional hazards (PH) regression models were employed to evaluate the effects of GBV-C and herpes viruses (CMV, EBV, HHV6, HHV8) on time from HIV-1 seroconversion to AIDS development. In addition, Gray’s piecewise constant time-varying coefficient (PC-TVC) model that accounts for varying covariate effects over time was employed to estimate the effects for the variables that did not follow PH assumption. Results: In Cox PH model analysis, GBV-C coinfection delayed AIDS development statistically significant in HIV-1 seroconverters. The log10 GBV-C RNA increase was associated with a 15% decrease in AIDS development, while the high HHV8 and CMV reactivation increased AIDS development respectively. The effects of HHV6 and EBV on AIDS development were not statistically significant. Using Gray PC-TVC model, GBV-C coinfection was associated with delaying AIDS development, especially starting from year 3 of HIV-1 infection, then the hazard ratios decreased over time until 10 years, and kept in low level after 10 years of infection. HHV8 reactivation increased the chance of AIDS development, especially after 3 years of HIV-1 infection. The effect of CMV reactivation was constant with a hazard ratio of 1.38. In addition, two variables, age and baseline CD4+ T cell counts, which were not statistically significant in Cox PH regression model analysis, were statistically significant in Gray PC-TVC model. Similar to Cox PH analysis, the effects of HHV6 and EBV were not statistically significant either on AIDS development. Conclusion: GBV-C co-infection delayed HIV-1 disease progression. HHV8 and CMV accelerated AIDS development. The effects of HHV6 and EBV were not statistically significant on AIDS development. Public health importance: This study has important implications for investigating viral coinfections on AIDS development and providing alternative ideas to delay HIV disease progression

Origin and Dynamics of HIV-1 Subtype C Infection in India

Objective: To investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India. Design: Ninety HIV-1 subtype C env gp120 subtype C sequences from India were compared with 312 env gp120 reference subtype C sequences from 27 different countries obtained from Los Alamos HIV database. All the HIV-1 subtype C env gp120 sequences from India were used for the geographical origin analysis and 61 subtype C env gp120 sequences with known sampling year (from 1991 to 2008) were employed to determine the origin of HIV infection in India. Methods: Phylogenetic analysis of HIV-1 env sequences was used to investigate the geographical origin and tMRCA of Indian HIV-1 subtype C. Evolutionary parameters including origin date and demographic growth patterns of Indian subtype C were estimated using a Bayesian coalescent-based approach under relaxed molecular clock models. Findings: The majority of the analyzed Indian and South African HIV-1 subtype C sequences formed a single monophyletic cluster. The most recent common ancestor date was calculated to be 1975.56 (95% HPD, 1968.78-1981.52). Reconstruction of the effective population size revealed three phases of epidemic growth: an initial slow growth, followed by exponential growth, and then a plateau phase approaching present time. Stabilization of the epidemic growth phase correlated with the foundation of National AIDS Control Organization in India. Interpretation: Indian subtype C originated from a single South African lineage in the middle of 1970s. The current study emphasizes not only the utility of HIV-1 sequence data for epidemiological studies but more notably highlights the effectiveness of community or government intervention strategies in controlling the trend of the epidemic. © 2011 Shen et al

Growth, chemical components and ensiling characteristics of king grass at different cuttings

In order to effectively use and ensile king grass (Pennisetum purpureum × Pennisetum americanum), the present research investigated growth rate, yield, chemical components and silage fermentation quality of different cuttings. King grass was harvested four times, and the 1st and 3rd cuttings were ensiled directly or after wilting for 12 and 24 h. The results showed that the dry matter daily growth of 2nd cutting was significantly higher than that of other cuttings, and the 4th cutting was the lowest (P < 0.05). The contents of crude protein (CP), crude fat and water-soluble carbohydrates (WSC) tended to reduce, and crude ash tended to increase with the increase of cutting times. All four cuttings of king grass had higher WSC content, lower buffer capacity and much lactic acid bacteria, the silages made from unwilted 1st cutting and 3rd cutting were of good fermentation quality, indicated by low pH values and high V-scores. Wilting had different effects on the 1st cutting and 3rd cutting silages in pH value and NH3-N content, the 1st cutting silage tended to increase the pH values and NH3-N content, with moisture content reduction, while the 3rd cutting silage tended to reduce NH3-N content and its pH value was not affected by wilting (P > 0.05). Although the 3rd cutting silage had better aerobic stability than the 1st cutting silage, they all were not stable within 6 days of aerobic exposure. Considering the contents of CP, crude fat, crude fiber, crude ash and WSC, the 1st cutting of king grass might have best nutrient value, while the 4th cutting was contrary. Different cuttings of king grass could be well preserved by natural fermentation, but their aerobic stability was poor.Keywords: Cuttings, ensiling, king grass, nutrient component, wiltin

Fluorescent sensing of mercury(II) based on formation of catalytic gold nanoparticles

A fluorescence assay for the highly sensitive and selective detection of Hg2+ using a gold nanoparticle (AuNP)-based probewas proposed. The assay was based on the formation of Hg-Au alloys, which accelerated the oxidization of o-phenylenediamine by dissolved oxygen to produce 2,3-diaminophenazine, a fluorescent product.;A fluorescence assay for the highly sensitive and selective detection of Hg2+ using a gold nanoparticle (AuNP)-based probewas proposed. The assay was based on the formation of Hg-Au alloys, which accelerated the oxidization of o-phenylenediamine by dissolved oxygen to produce 2,3-diaminophenazine, a fluorescent product

Evaluation of Cervical Mucosa in Transmission Bottleneck during Acute HIV-1 Infection Using a Cervical Tissue-Based Organ Culture

Background: Although there are different strains of HIV-1 in a chronically infected individual, only one or limited virus strains are successfully transmitted to a new individual. The reason for this "transmission bottleneck" is as yet unknown. Methodology/Principal Findings: A human cervical explant model was used to measure HIV-1 transmission efficiency of viral strains from chronic infections, and transmitter/founder variants. We also evaluated the genetic characteristics of HIV-1 variants in the inoculums compared to those transmitted across the cervical mucosa. Eight different HIV-1 isolates were used in this study, six chronic isolates and two transmitter/founder viruses. The transmission efficiency of the chronic and transmitter/founder virus isolates and the viral diversity of chronic isolates before and after viral transmission were assessed. The results indicate that transmitter/founder viruses did not display higher transmission efficiency than chronic HIV-1 isolates. Furthermore, no evidence for a difference in diversity was found between the inoculums and transmitted virus strains. Phylogenetic analysis indicated that the sequences of variants in the inoculums and those present in transmitted virus intermingled irrespective of co-receptor usage. In addition, the inoculum and transmitted variants had a similar pairwise distance distribution. Conclusion: There was no selection of a single or limited number of viral variants during HIV-1 transmission across the cervical mucosa in the organ culture model, indicating that the cervical mucosa alone may not produce the transmission bottleneck of HIV-1 infection observed in vivo. © 2012 Shen et al

Oral Cytokine Levels Are More Linked to Levels of Plasma and Oral HIV-1 RNA Than to CD4+ T-Cell Counts in People With HIV.

BackgroundWe determined the levels of 11 soluble immune mediators in oral washings of AIDS Clinical Trials Group A5254 participants with varying degrees of plasma viremia and CD4 T-cell counts to characterize the mucosal immune response at different stages of HIV-1 infection.MethodsA5254 was a multicenter, cross-sectional study in people with HIV (PWH) recruited into 4 strata based on CD4 count and levels of plasma viremia: stratum (St) A: CD4 ≤200 cells/mm3, HIV-1 RNA (viral load [VL]) >1000 cps/mL; St B: CD4 ≤200, VL ≤1000; St C: CD4 >200, VL >1000; St D: CD4 >200, VL ≤1000. Oral/throat washings were obtained from all participants. Soluble markers were tested in oral/throat washings using a multibead fluorescent platform and were compared across strata. Linear regression was used to determine the associations between cytokines and HIV-1 in plasma and oral fluid.ResultsSt A participants had higher levels of interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) compared with St B and D (P = .02; P < .0001) but were not different from St C. IL-8, IL-10, and IL-12 were elevated in St A compared with the other 3 strata (P = .046; P < .0001). Linear regression demonstrated that oral HIV-1 levels were associated with IL-1β, IL-6, IL-8, and TNFα production (R > .40; P < .001) when controlling for CD4 count and opportunistic infections.ConclusionsOur results show that high levels of oral HIV-1, rather than low CD4 counts, were linked to the production of oral immune mediators. Participants with AIDS and uncontrolled viremia demonstrated higher levels of pro- and anti-inflammatory soluble immune mediators compared with participants with lower HIV-1 RNA. The interplay of HIV-1 and these immune mediators could be important in the oral health of PWH

Detection of HIV-1 RNA/DNA and CD4 mRNA in feces and urine from chronic HIV-1 infected subjects with and without anti-retroviral therapy

HIV-1 infects gut associated lymphoid tissues (GALT) very early after transmission by multiple routes. The infected GALT consequently serves as the major reservoir for HIV-1 infection and could constantly shed HIV-1 and CD4+ T cells into the intestinal lumen. To examine this hypothesis, we monitored HIV-1 RNA/DNA and CD4 mRNA in fecal samples of chronically infected subjects with and without antiretroviral therapy (ART). We compared this to levels of HIV-1 RNA/DNA in urine and blood from the same subjects. Our results show that HIV-1 DNA, RNA and CD4 mRNA were detected in 8%, 19% and 31% respectively, of feces samples from infected subjects with detectable plasma viral load, and were not detected in any of subjects on ART with undetectable plasma viral load. In urine samples, HIV-1 DNA was detected in 24% of infected subjects with detectable plasma viral load and 23% of subjects on ART with undetectable plasma viral load. Phylogenetic analysis of the envelope sequences of HIV-1 revealed distinct virus populations in concurrently collected serum, feces and urine samples from one subject. In addition, our study demonstrated for the first time the presence of CD4 mRNA in fecal specimens of HIV-1 infected subjects, which could be used to assess GALT pathogenesis in HIV-1 infection

Genetic characterization of HIV-1 from semen and blood from clade C-infected subjects from India and effect of therapy in these body compartments

AbstractBiologic and genetic differences between HIV-1 clade C in India and clade B in US suggest that the effect of anti-viral therapy in various body compartments may differ between these two clades. We examined the effect of therapy on viral loads in semen and blood of HIV-1-clade C infected subjects from India and evaluated whether HIV-1 in the semen is different from that in blood in these subjects. HIV-1 RNA was detected in semen and blood at all stages of the disease. Viral loads in semen and blood were strongly correlated with each other, but not with the CD4+ T cell count. Anti-viral treatment reduced viral load drastically in blood and semen within one month of post therapy. Genetic characterization of HIV-1 in the semen and blood demonstrated that they were highly compartmentalized. These data have important implications of sexual transmission of HIV-1 in clade C HIV-1 infected subjects

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values