Neutralization Characteristics of HIV-1 CRF01_AE Env Clones From Infections in China

Owing to the increasing prevalence of HIV-1 CRF01_AE, it is necessary to understand the neutralization properties of CRF01_AE and to develop broadly neutralizing monoclonal antibodies (bnmAbs) that can neutralize this virus. The full-length Env gene was cloned from HIV-1 CRF01_AE-infected plasma specimens collected in China and used to establish pseudoviruses. Neutralization phenotypes of the pseudoviruses were characterized with bnmAbs. The neutralizing activities of 11 bnmAbs VRC01, VRC03, IgG1b12 and 3BNC117 (targeting the CD4 binding site); PG9 (targeting the V1V2 region); 2G12 (targeting the high mannose patch), PGT135 and 10-1074 (targeting the V3 glycans); 2F5, 4E10 and 10E8 (targeting the membrane proximal external region), against 36 pseudoviruses were analyzed, demonstrating varying efficacies. In general, VRC01, 10E8 and 3BNC117 showed strong neutralizing activity, neutralizing more than 75% of the pseudoviruses; followed by PG9 and 4E10, showing moderate neutralizing activity with neutralization of 50%–60% of the pseudoviruses; whereas the efficacies of the remaining bnmAbs were poor, neutralizing less than 15% of pseudoviruses tested. Env variants of CRF01_AE from one infection also showed significant differences in resistance to neutralization. These characterized HIV-1 CRF01_AE pseudoviruses could be used for neutralization studies and evaluation of vaccines or anti-HIV-1 products in China.

Neutralization Characteristics HIV-1 CRF01_AE Env Clones from Infections in China

Owing to the increasing prevalence of HIV-1 CRF_01AE, it is necessary to understand the neutralization properties of CRF_01AE and to develop broadly neutralizing monoclonal antibodies (bnmAbs) that can neutralize this virus. The full-length Env gene was cloned from HIV-1 CRF01_AE-infected plasma specimens collected in China and used to establish pseudoviruses. Neutralization phenotypes of the pseudoviruses were characterized with bnmAbs. The neutralizing activities of 11 bnmAbs VRC01, VRC03, IgG1b12 and 3BNC117 (targeting the CD4 binding site); PG9 (targeting the V1V2 region); 2G12 (sugar chain specific), PGT135 and 10-1074 (targeting the V3 region); 2F5, 4E10 and 10E8 (targeting the membrane proximal external region), against 36 pseudoviruses were analyzed, demonstrating varying efficacies. In general, VRC01, 10E8 and 3BNC117 showed strong neutralizing activity, neutralizing more than 75% of the pseudoviruses; followed by PG9 and 4E10, showing moderate neutralizing activity with neutralization of 50%–60% of the pseudoviruses; whereas the efficacies of the remaining bnmAbs were poor, neutralizing less than 15% of pseudoviruses tested. Env variants of CRF_01AE also showed significant differences in resistance to neutralization. CRF_01AE Env variants pose a serious challenge for the development of bnmAbs and vaccines, and these characterized HIV-1 CRF_01AE pseudoviruses could be used for neutralization studies and evaluation of vaccines or anti-HIV-1 products in China.

The interfacial energy of metallic nanoparticles on the boundary with polyatomic alcohols

The interface energy is general factor, which has determined the critical size and equilibrium shape of nanoparticles, velocity of its growth and stability. The electron-statistical method, based on the Thomas-Fermi theory taking into account its current state, allows one to calculate the interfacial energy of metallic objects of different dimensions at the boundary with various media. Based on this method, we have developed a variant for calculating the interfacial energy of the system « low-dimensional metallic phase - polar dielectric film». The polyatomic alcohols (diols), used, for example, as non-aqueous media for the synthesis of metal nanoparticles, were chosen as the external medium. Also we have chosen cobalt nanocrystals as a low-dimensional metallic phase. Expressions are obtained for the external and internal contributions to the interfacial energy of the system, including the polarization correction, due to the presence of a dielectric fluid in the external region of the system. The effect of a limited dielectric fluid layer on the Gibbs boundary coordinate is analyzed. The presence of a dielectric leads to a shift of the Gibbs boundary to the external region of the system, that is, the so-called effect of «pulling the tail» of the electron density is observed. It is shown that with increasing dielectric constant, the magnitude of the polarization contribution increases rapidly in magnitude. The interface energy of a cobalt nanocrystal at the interface with polar polyatomic alcohols is calculated. The interfacial energy of the faces of cobalt nanocrystals decreases nonlinearly with an increase in the linear dimensions of the metal phase. It is shown that the dielectric coating changes the character of the dimensional and orientational dependence in comparison with the interfacial energy of macrocrystals and thin films at the interface with vacuum. With a constant size of the metal phase and an increase in the thickness of the dielectric coating, the interface energy of faces and anisotropy increase. It has been established that 1,2-ethanediol is the most effective surfactant for cobalt particles of the polyatomic alcohols considered in this paper. The dependencies obtained in this work are consistent with the literature data for the thin films of alkaline metals and other system.

Asymmetric transport costs and welfare implications through a firm-delocation effect

PurposeWith the use of a two-region monopolistically competitive model, the paper primarly studies how unilateral changes in a country's intra-regional and/or inter-national transport costs affect its own and its trading partner's welfare. Moreover, by considering a three-region monopolistically competitive model that consists of an external region and two integrated regions, with the one having a location advantage with respect to the external market, the paper studies how within-country asymmetries in transport costs affect trading partner's welfare.Design/methodology/approachThis paper examines how investments in the infrastructure affect welfare in the home country and in its trading partner by primarily using a model with direction-specific intra-regional and inter-national trade costs. Moreover, it focuses on the within-country asymmetries in transportation costs and their impacts on trading partners' welfare.FindingsThe first model shows that a unilateral reduction in a country's transport costs is beneficial for its domestic firms, while it hurts firms located in its trading partner country. Other findings show that an equal bilateral reduction in inter-national transport costs is a Pareto improvement, since it is beneficial for both countries. The second model shows that a reduction in intra-regional transport costs benefits the two integrated regions, while it has no impact on the welfare of the external region.Originality/value Two monopolistically competitive models are considered, in order to study how investments in the infrastructure affect welfare in the home country and in its trading partner. Interestingly, the models sheds light on an important mechanism, that of firm-delocation effect.

Unique Genotypic Features of HIV-1 C Gp41 Membrane Proximal External Region Variants during Pregnancy Relate to Mother-to-child Transmission via Breastfeeding

ABSTRACTMother-to-child transmission (MTCT) through breastfeeding remains a major source of pediatric HIV-1 infection worldwide. To characterize plasma HIV-1 subtype C populations from infected mothers during pregnancy that related to subsequent breast milk transmission, an exploratory study was designed to apply next generation sequencing and a custom bioinformatics pipeline for HIV-1 gp41 extending from heptad repeat region 2 (HR2) through the membrane proximal external region (MPER) and the membrane spanning domain (MSD). Viral populations during pregnancy from women who transmitted by breastfeeding, compared to those who did not, displayed greater biodiversity, more frequent amino acid polymorphisms, lower hydropathy index and greater positive charge. Viral characteristics were restricted to MPER, failed to extend into flanking HR2 or MSD regions, and were unrelated to predicted neutralization resistance. Findings provide novel parameters to evaluate an association between maternal MPER variants present during gestation and lactogenesis with subsequent transmission outcomes by breastfeeding.IMPORTANCEHIV-1 transmission through breastfeeding accounts for 39% of MTCT and continues as a major route of pediatric infection in developing countries where access to interventions for interrupting transmission is limited. Identifying women who are likely to transmit during breastfeeding would focus therapies during the breastfeeding period to reduce MTCT. Findings from our pilot study identify novel characteristics of gestational viral MPER quasispecies related to transmission outcomes and raise the possibility for predicting MTCT by breastfeeding based on identifying mothers with high-risk viral populations.

Predicted 3D Models of the SARS-CoV-2 Spike Protein Membrane Proximal External Region and Transmembrane Domain

The transmembrane helix domain (TMD), membrane proximal external region (MPER) and part of heptad repeat 2 (HR2) domain in SARS-CoV-2 spike protein were modelled using a constrained fold-and-dock strategy. The resulting structures were clustered and their large scale pose variability and energy landscape is described; several representative models are discussed. The results suggest considerable flexibility in the conformation of those regions, which may have an important role in the ability of spike protein to fuse the cell and viral membranes.