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The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.

The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.

The latent HIV-1 reservoir is the key obstacle for curing HIV-1 infection, but the timepoint at which the HIV-1 reservoir is established is currently unclear. Here, Whitney et al. show in non-human primates that the SIV reservoir in CD4+ T cells is seeded within the first 2 days after infection.

The main purpose of this research was to evaluate and analyze the economic value of the meteorological information services (MIS) provided by the Central Weather Bureau (CWB) when applied to aquaculture in Taiwan. In this research, a contingent valuation method (CVM) was used to inquire about the subjective rating given to the CWB’s meteorological information services based on the responses to a national level questionnaire distributed among aquaculture farmers. The subjective rating revealed how the aquaculture farmers rated the accuracy of the MIS provided by the CWB and how they recognized the impact of the MIS on their aquaculture output. On this basis, this research determined the economic value brought about by the application of the meteorological information services. In order to understand the main factors affecting the respondents’ willingness-to-pay (WTP) for the MIS, this research also conducted an empirical estimation of the bid function. The results indicated that the main factors affecting the WTP were found to include the respondents’ subjective rating of the meteorological information services (including the accuracy rating and the effect rating), traditional social and economic background variables such as income and education level, as well as fish species. In addition, through testing the estimation of the bid function, it was also found that the survey sample used in this research had a significant starting point bias effect, which needed to be corrected using econometric methods. According to the empirical results, the median willingness-to-pay (WTP) of aquaculture farmers in Taiwan was 3544 New Taiwan Dollars (NTD)/person/year and the total economic value at the national level ranged from 157 million to 209 million NTD per year. Since the MIS service users have often lacked sufficient knowledge and ability to interpret the weather forecasts, how to strengthen the capabilities of service users in using MIS through the promotion of training programs and improve the value of the MIS may be an important policy insight.

In this paper, we explore the effect of using different convolutional layers, batch normalization and the global average pooling layer upon a convolutional neural network (CNN) based gaze tracking system. A novel method is proposed to label the participant’s face images as gaze points retrieved from eye tracker while watching videos for building a training dataset that is closer to human visual behavior. The participants can swing their head freely; therefore, the most real and natural images can be obtained without too many restrictions. The labeled data are classified according to the coordinate of gaze and area of interest on the screen. Therefore, varied network architectures are applied to estimate and compare the effects including the number of convolutional layers, batch normalization (BN) and the global average pooling (GAP) layer instead of the fully connected layer. Three schemes, including the single eye image, double eyes image and facial image, with data augmentation are used to feed into neural network to train and evaluate the efficiency. The input image of the eye or face for an eye tracking system is mostly a small-sized image with relatively few features. The results show that BN and GAP are helpful in overcoming the problem to train models and in reducing the amount of network parameters. It is shown that the accuracy is significantly improved when using GAP and BN at the mean time. Overall, the face scheme has a highest accuracy of 0.883 when BN and GAP are used at the mean time. Additionally, comparing to the fully connected layer set to 512 cases, the number of parameters is reduced by less than 50% and the accuracy is improved by about 2%. A detection accuracy comparison of our model with the existing George and Routray methods shows that our proposed method achieves better prediction accuracy of more than 6%.

The cellular endosomal sorting complex required for transport (ESCRT) machinery participates in membrane scission and cytoplasmic budding of many RNA viruses. Here, we found that expression of dominant negative ESCRT proteins caused a blockade of Epstein-Barr virus (EBV) release and retention of viral BFRF1 at the nuclear envelope. The ESCRT adaptor protein Alix was redistributed and partially colocalized with BFRF1 at the nuclear rim of virus replicating cells. Following transient transfection, BFRF1 associated with ESCRT proteins, reorganized the nuclear membrane and induced perinuclear vesicle formation. Multiple domains within BFRF1 mediated vesicle formation and Alix recruitment, whereas both Bro and PRR domains of Alix interacted with BFRF1. Inhibition of ESCRT machinery abolished BFRF1-induced vesicle formation, leading to the accumulation of viral DNA and capsid proteins in the nucleus of EBV-replicating cells. Overall, data here suggest that BFRF1 recruits the ESCRT components to modulate nuclear envelope for the nuclear egress of EBV.

The article discusses a study related to exploration of single Broadly neutralizing antibodies (bNAbs) selection for resistant simian-HIV (SHIV) variants in prophylactic and therapeutic experiments in rhesus monkeys. It mentions single bNAbs efficiently select resistant viruses for establishing infection and demonstrating importance of bNAb cocktails for HIV-1 prevention and V3 glycan-dependent antibody PGT121 alone failing to protect against a mixed challenge with SHIV-SF162P3 and SHIV-325c.

The implications of the international demonstration effect (IDE) for the development of underdeveloped economies have long been studied and debated. Yet few formal analyses exist in the literature, especially regarding its implications for the growth of domestic markets and the division of labour in developing economies. We offer an analysis of endogenous specialization under the IDE, the first of its kind, showing that, far more complicated than the scenario held by conventional wisdom, the IDE makes more difficult the emergence of the market underpinning the domestic division of labour, but facilitates the expansion of the market once it has been developed. [ABSTRACT FROM AUTHOR]

Simian-human immunodeficiency virus (SHIV) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (HIV-1) vaccines, therapeutics, and cure strategies. SHIVs have been optimized by incorporating HIV-1 Env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (SIV) Env to improve rhesus CD4 binding. We applied this strategy to three SHIV challenge stocks (SHIVSF162p3, SHIV-AE16, and SHIV-325c) and observed three distinct outcomes. We constructed six Env375 variants (M, H, W, Y, F, and S) for each SHIV, and we performed a pool competition study in rhesus monkeys to define the optimal variant for each SHIV prior to generating large-scale challenge stocks. We identified SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH as the optimal variants. SHIV-SF162p3S could not be improved, as it already contained the optimal Env375 residue. SHIVAE16W exhibited a similar replicative capacity to the parental SHIV-AE16 stock. In contrast, SHIV-325cH demonstrated a 2.6-log higher peak and 1.6-log higher setpoint viral loads than the parental SHIV-325c stock. These data demonstrate the diversity of potential outcomes following Env375 modification in SHIVs. Moreover, the clade C SHIV-325cH challenge stock may prove useful for evaluating prophylactic or therapeutic interventions against clade C HIV-1. [ABSTRACT FROM AUTHOR]

Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vectorbased production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo. Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. [ABSTRACT FROM AUTHOR]

The cellular endosomal sorting complex required for transport (ESCRT) was recently found to mediate important morphogenesis processes at the nuclear envelope (NE). We previously showed that the Epstein-Barr virus (EBV) BFRF1 protein recruits the ESCRT-associated protein Alix to modulate NE structure and promote EBV nuclear egress. Here, we uncover new cellular factors and mechanisms involved in this process. BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. BFRF1 is ubiquitinated, and elimination of possible ubiquitination by either lysine mutations or fusion of a deubiquitinase hampers NE-derived vesicle formation and virus maturation. While it interacts with multiple Nedd4-like ubiquitin ligases, BFRF1 preferentially binds Itch ligase. We show that Itch associates with Alix and BFRF1 and is required for BFRF1-induced NE vesicle formation. Our data demonstrate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE and EBV maturation, uncovering novel regulatory mechanisms of nuclear egress of viral nucleocapsids. [ABSTRACT FROM AUTHOR]