Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5

Infection by HIV-1 most often results from the successful transmission and propagation of a single virus variant, termed the transmitted/founder (T/F) virus. Here, we compared the attachment and entry properties of envelope (Env) glycoproteins from T/F and chronic control (CC) viruses. Using a panel of 40 T/F and 47 CC Envs, all derived by single genome amplification, we found that 52% of clade C and B CC Envs exhibited partial resistance to the CCR5 antagonist maraviroc (MVC) on cells expressing high levels of CCR5, while only 15% of T/F Envs exhibited this same property. Moreover, subtle differences in the magnitude with which MVC inhibited infection on cells expressing low levels of CCR5, including primary CD4⁺ T cells, were highly predictive of MVC resistance when CCR5 expression levels were high. These results are consistent with previous observations showing a greater sensitivity of T/F Envs to MVC inhibition on cells expressing very high levels of CCR5 and indicate that CC Envs are often capable of recognizing MVC-bound CCR5, albeit inefficiently on cells expressing physiologic levels of CCR5. When CCR5 expression levels are high, this phenotype becomes readily detectable. The utilization of drug-bound CCR5 conformations by many CC Envs was seen with other CCR5 antagonists, with replication-competent viruses, and did not obviously correlate with other phenotypic traits. The striking ability of clade C and B CC Envs to use MVC-bound CCR5 relative to T/F Envs argues that the more promiscuous use of CCR5 by these Env proteins is selected against at the level of virus transmission and is selected for during chronic infection.     

Morphometric and phytochemical characterization of chaura fruits (Gaultheria pumila): a native Chilean berry with commercial potential

Background

For the first time, a morphometric characterization of chaura (Gaultheria pumila) fruits has been conducted between natural populations growing in the Villarrica National Park, Araucania Region, Chile. Chaura is a native Ericaceae from Chile that produces aromatic and tasty fruits which could be of agricultural interest.

Results

To influence the decision for a further domestication of G. pumila, both the fruit sizes (indicator of productivity) and the nutritional properties of the fruits have been determined from different subpopulations. Samples were a total of 74 plants and 15 fruits per plant which were randomly harvested following its natural distribution around the Villarrica volcano. Altogether, fresh weight, shape, color, diameter in the pole and the equatorial dimensions were determined as phenotypic traits of the G. pumila fruits. Meanwhile the total soluble solids, anthocyanin and pectin contents were calculated as nutritional traits of the Chaura fruits. Results showed a high phenotypic diversity between the sampled population with three main fruit shapes and three predominant colors. The round shapes were the most abundant, whereas a significant correlation was found among fruit size with weight and color. The highest fresh weight (597.3 mg), pole diameter (7.1 mm) and equatorial diameter (6.5 mm) were estimated in the pink color fruits.

Conclusions

The total amount of anthocyanin was higher in red fruits, while the maximum pectin content was obtained in the round white fruits. Overall results must pave the way for a further domestication and introduction of the Chaura species in the agro-productive system in Chile.     

Tuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces

Although tuft cells were discovered over 60 years ago, their functions have long been enigmatic, especially in human health. Nonetheless, tuft cells have recently emerged as key orchestrators of the host response to diverse microbial infections in the gut and airway. While tuft cells are epithelial in origin, they exhibit functions akin to immune cells and mediate important interkingdom interactions between the host and helminths, protists, viruses, and bacteria. With broad intra- and intertissue heterogeneity, tuft cells sense and respond to microbes with exquisite specificity. Tuft cells can recognize helminth and protist infection, driving a type 2 immune response to promote parasite expulsion. Tuft cells also serve as the primary physiologic target of persistent murine norovirus (MNV) and promote immune evasion. Recently, tuft cells were also shown to be infected by rotavirus. Other viral infections, such as influenza A virus, can induce tuft cell–dependent tissue repair. In the context of coinfection, tuft cells promote neurotropic flavivirus replication by dampening antiviral adaptive immune responses. Commensal and pathogenic bacteria can regulate tuft cell abundance and function and, in turn, tuft cells are implicated in modulating bacterial infiltration and mucosal barrier integrity. However, the contribution of tuft cells to microbial sensing in humans and their resulting effector responses are poorly characterized. Herein, we aim to provide a comprehensive overview of microbial activation of tuft cells with an emphasis on tuft cell heterogeneity and differences between mouse and human tuft cell biology as it pertains to human health and disease.     

Aspects and altitudes modify the requirement of disturbance in oak (Quercus leucotrichophora A. Camus) belt of Garhwal Himalaya

Present study measures the impact of forest disturbance on population structure and regeneration status of a Himalayan banj oak (Qsuercus leucotrichophora A. Camus) forest at different aspects and altitudes. The whole study was carried out by placing 300 systematically selected sample plots in banj oak forest. The study revealed that moderately disturbed forest patches were present in all elevation ranges and both north and south facing aspects whereas most of the highly disturbed patches were situated near middle and lower stretches of forests or close to habitations. Density of primary diameter class (5–15 cm) was recorded highest in moderately disturbed zone in upper elevation ranges and north facing aspect and ‘fair’ category of regeneration was most frequent in all elevation ranges and aspects. The paper concludes a positive effect of mid-level disturbance on plant community for better regeneration and study recommends a minimum resource extraction and silvicultural practices in banj-oak belt of Himalaya for a minimum canopy opening which not only be able to provide biomass to local communities for their daily needs but also would be able to maintain and improve forest health.     

Natural refuge crops,buildup of resistance,and zero-refuge strategy for Bt cotton in China

In the context of genetically modified crops expressing the Bacillus thuringiensis (Bt) toxin, a ‘refuge’ refers to a crop of the same or a related species that is planted nearby to enable growth and reproduction of the target pest without the selection pressure imposed by the Bt toxin. The goal of this study is to discuss the role of natural refuge crops in slowing down the buildup of resistance of cotton bollworm (CBW), and to evaluate China’s no-refuge policy for Bt cotton. We describe in detail the different factors that China should consider in relation to the refuge policy. Drawing on a review of scientific data, economic analyses of other cases, and a simulation exercise using a bio-economic model, we show that in the case of Bt cotton in China, the no-refuge policy is defensible.     

Governance in the Face of Extreme Events: Lessons from Evolutionary Processes for Structuring Interventions,and the Need to Go Beyond

Ecosystems - The increasing frequency of extreme events, exogenous and endogenous, poses challenges for our societies. The current pandemic is a case in point; but "once-in-a-century"...     

Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid

Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide. This nucleotide change resulted in amino acid substitution F514I in the viral capsid, which led to >10,000-fold higher replication in systemic organs including the brain. Pathogenicity was mediated by enhanced recruitment and infection of intestinal myeloid cells and increased extraintestinal dissemination of virus. Interestingly, the trade-off for this mutation was reduced fitness in an IFN-competent host, in which CR6 bearing F514I exhibited decreased intestinal replication and shedding. In an immunodeficient context, a spontaneous amino acid change can thus convert a relatively avirulent viral strain into a lethal pathogen.