NTB-A and 2B4 Natural Killer Cell Receptors Modulate the Capacity of a Cocktail of Non-Neutralizing Antibodies and a Small CD4-Mimetic to Eliminate HIV-1-Infected Cells by Antibody-Dependent Cellular Cytotoxicity.

Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion of antibodies; NK cell activation is further sustained by the co-engagement of activating receptors NTB-A and 2B4. During HIV-1 infection, Nef and Vpu accessory proteins contribute to ADCC escape by downregulating the ligands of NTB-A and 2B4. HIV-1 also evades ADCC by keeping its envelope glycoproteins (Env) in a "closed" conformation which effectively masks epitopes recognized by non-neutralizing antibodies (nnAbs) which are abundant in the plasma of people living with HIV. To achieve this, the virus uses its accessory proteins Nef and Vpu to downregulate the CD4 receptor, which otherwise interacts with Env and exposes the epitopes recognized by nnAbs. Small CD4-mimetic compounds (CD4mc) have the capacity to expose these epitopes, thus sensitizing infected cells to ADCC. Given the central role of NK cell co-activating receptors NTB-A and 2B4 in Fc-effector functions, we studied their contribution to CD4mc-mediated ADCC. Despite the fact that their ligands are partially downregulated by HIV-1, we found that both co-activating receptors significantly contribute to CD4mc sensitization of HIV-1-infected cells to ADCC.

Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu.

Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for the mechanisms of their biological functions as well as their potential as therapeutic targets.

Analyses on antigen epitopes and drug resistance mutations of HIV-1 gag and pol genes / 病毒学报

To study the CTL antigen epitopes and drug resistance mutations of HIV-1 gag and pol genes through analyzing gag and pol gene sequences. The HIV-1 gag and pol gene fragments were amplified using nested polymerase chain reaction. A total of 23 PCR sequences, 449 cloned gag sequences and 402 cloned pol sequences were obtained. Sequence analyses showed the 23 samples were subtype B or B'. A total of 4 in 8 CTL antigen epitopes appeared 8 mutations in consensus sequence of subtype B and B'. There were no mutations found in the PCR sequences, whereas a few mutations were found in clone sequences (9.80%) in 5 antigen epitopes in p24 region. Eighteen PIs-related mutations and 24 RTIs-related mutations were found in PCR sequences and clone sequences in pol gene region, in which 17 (94.44%) PIs-related mutations and 15 (62.50%) RTIs-related mutations were found only in the clone sequences, respectively. The results showed that the prevalence of HIV-1 drug resistance strains in this study was at a higher level (17.39%), suggesting that some samples were resistant.to existing antiviral drugs.

Establishment of a high-throughput screening assay for interaction inhibitor between BST-2 and Vpu / 病毒学报

BST-2 plays an important role in host innate immune response via inhibiting the release of HIV-1. HIV-1 accessory protein Vpu can interact with BST-2 through its transmembrane domains, degrade BST-2, and decrease BST-2 that are transported to the cell surface, thus anti-virus function of BST-2 is antagonized. In our study, we constructed plasmid RB connecting Rluc to the N-termimal of BST-2, and plasmid VE connecting EYFP to the C-terminal of Vpu. The two fusion proteins were co-expressed in 293 cells, and the interaction between the two proteins was detected via BRET method. And we further established a stable 293 cell line of dual-expression. By using BRET method, and the interaction between BST-2 and Vpu transmembrane domain as the target, a high-throughput screening assay was created that was expected to seek novel interaction inhibitors.

Macronutrientes: relación inversa entre consumo de proteínas vegetales y presión arterial de adolescentes que acuden al Centro de Atención a Pacientes con Enfermedades Infectocontagiosas "Dra. Elsa La Corte" Facultad de Odontología (CAPEI/UCV) / Macronutrients: inverse relationship between vegetable protein intake and blood preassure of adolescents that attend CAPEI/UCV

Existen evidencias que apuntan a la existencia de una asociación inversa entre la ingesta de proteínas vegetales y la presión arterial. En este estudio, los datos de adolescentes VIH +, que acuden a la consulta del Centro de Atención a Pacientes con Enfermedades Infectocontagiosas "Dra. Elsa La Corte" (CAPEI) de la Universidad Central de Venezuela (UCV), fueron analizados para estudiar la relación entre el consumo de proteínas vegetales y la presión arterial tanto sistólica como diastólica, ajustando por índice de masa corporal (IMC) y consumo de energía. Estudio transversal en 43 adolescentes VIH+ con edades entre 15 y 18 años en ambos sexos, que acudieron al CAPEI en el año 2009. Se analizó la media de dos lecturas obtenidas con 5 minutos de intervalo en una visita. Se determinaron peso y altura y se calculó el IMC. Para la determinación de la ingesta de proteínas vegetales se aplicó la técnica de recordatorio de 24 horas. El análisis estadístico se basó en el modelo de regresión lineal. Los resultados muestran una asociación negativa y significativa entre el consumo de proteínas vegetales y la presión arterial sistólica y diastólica, después de ajustar por consumo de energía e IMC, las diferencias de presión arterial sistólica y diastólica asociada con una ingesta de proteínas vegetales de 57,6 kilocalorías por ciento (variación intercuartil) fue de -2,8 mm Hg y -2,4 mm Hg, respectivamente (p <0,05 para ambos). La promoción y planificación de dietas con altos contenidos de proteínas vegetales puede ser de utilidad para prevenir y controlar valores elevados de la presión arterial

Data are available that indicate an independent inverse relationship of dietary vegetable protein to blood pressure (BP). In this investigation data from HIV adolescents attending CAPEI/UCV, were analyzed to study the relationship between dietary vegetable protein and systolic/diastolic pressures, with control for body mass index (BMI) and calorie intake. This was a cross-sectional study with 43 HIV adolescents 15 to 18 years of age. BP was measured 2 times at 1 visit; height and weight were measured, and BMI was calculated; dietary data were obtained from 24-hour dietary recalls. Multivariate regression was applied.The results showed that with control for BMI and calorie intake, estimated average BP differences associated with a vegetable protein intake that was higher by 57,6 %kcal (interquartile range) were -2,8 mm Hg systolic and -2,4 mm Hg diastolic (p <0,05 both). Broad improvement in diets high in vegetable protein can be important in preventing and controlling high blood pressure

Complete human immunodeficiency virus-1 specific T lymphocyte response to Chinese human immunodeficiency virus-1 B/C chronic infectors / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To characterize the human immunodeficiency virus (HIV) -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level.</p><p><b>METHODS</b>Twenty-five HIV-1B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef>Vpr>Gag>Pol>Vpu>Env>Rev>Vif>Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-gamma production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-l-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.</p>

Study on the relationship between the polymorphisms and secondary structure of tat exon-1 gene and HIV/ AIDS progress in subtype B' and B'/C / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the polymorphisms and secondary structure of human immunodeficiency virus (HIV-1) tat exon 1 among subtype B' and B'/C HIV-1 infected people in China and to explore the relationship between the polymorphism of tat exon 1 and the disease progression.</p><p><b>METHODS</b>8 subtype B' and 5 B'/C HIV-1 infected patients with slow disease progression were selected from Liaoning, Jilin and Yunnan province. 26 subtype B' and 9 B'/C HIV-1 infected patients with similar sex, age but with typical disease progression were selected. Provirus was extracted from the whole blood. The gene sequences of the Tat exon 1 were amplified by nest-polymerase chain reaction (nest-PCR). Products were purified and sequenced directly. The sequences were aligned, translated, amino acid substitution were analyzed and secondary structures were predicted.</p><p><b>RESULTS</b>Many amino acid substitution could be found in the exon 1 of Tat in HIV-1 subtype B' and B'/C recombinant strain infected persons with different disease progression except A58T,none of them showed definitely relationship with HIV viral load and disease progression. 23N, 31S, 32Y and 46F were subtype-specific substitutions. No characteristic secondary structure of exon 1 of Tat was found.</p><p><b>CONCLUSION</b>Some of the mutations of tat exon 1 might be related to HIV viral load and disease progression. However, there was no relationship found between the secondary structure of Tat protein and the disease progression.</p>