Gelsolin activity controls efficient early HIV-1 infection

HIV-1 entry into target lymphocytes requires the activity of actin adaptors that stabilize and reorganize cortical F-actin, like moesin and filamin-A. These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 Envelope (Env)-CD4/co-receptor interactions and that generates the tension at the plasma membrane necessary to potentiate fusion pore formation, thereby favouring early HIV-1 infection. However, it remains unclear whether the dynamic processing of F-actin and the amount of cortical actin available during the initial virus-cell contact are required to such events

Induction of both local immune response in mice and protection in a rabbit model by intranasal immunization with modified vaccinia ankara virus expressing a secreted form of bovine herpesvirus 1 glycoprotein D

In this study, we evaluated the immunogenicity and efficacy of mucosal delivery of a recombinant modified vaccinia Ankara virus (MVA) expressing the secreted version of bovine herpesvirus type 1 (BoHV-1) glycoprotein D (MVA-gDs) without addition of adjuvant in two animal models. First, we demonstrated the capability of MVA-gDs of inducing both local and systemic anti-gD humoral immune response after intranasal immunization of mice. Then, we confirmed that two doses of MVA-gDs administered intranasally to rabbits induced systemic anti-gD antibodies and conferred protection against BoHV-1 challenge. Our results show the potential of using MVA as a vector for the rational design of veterinary vaccines capable of inducing specific and protective immune responses both at local and systemic level.Inst. de BiotecnologíaFil: Del Medico Zajac, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zanetti, Flavia Adriana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esusy, María Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Federico, Carlos Rodolfo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zabal, Osvaldo Alfredo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Valera, Alejandro Rafael. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Cátedra de Virología; ArgentinaFil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentin

Viral characteristics associated with the clinical nonprogressor phenotype are inherited by viruses from a cluster of HIV-1 elite controllers

A small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs), display permanent control of viral replication and lack of clinical progression. This control is the result of a complex interaction of host, immune, and viral factors. We identified, by phylogenetic analysis, a cluster of LTNP-ECs infected with very similar low-replication HIV-1 viruses, suggesting the contribution of common viral features to the clinical LTNP-EC phenotype. HIV-1 envelope (Env) glycoprotein mediates signaling and promotes HIV-1 fusion, entry, and infection, being a key factor of viral fitness , cytopathicity, and infection progression Therefore, we isolated full-length genes from viruses of these patients and from chronically infected control individuals. Functional characterization of the initial events of the viral infection showed that Envs from the LTNP-ECs were ineffective in the binding to CD4 and in the key triggering of actin/tubulin-cytoskeleton modifications compared to Envs from chronic patients. The viral properties of the cluster viruses result in a defective viral fusion, entry, and infection, and these properties were inherited by every virus of the cluster. Therefore, inefficient HIV-1 Env functions and signaling defects may contribute to the low viral replication capacity and transmissibility of the cluster viruses, suggesting a direct role in the LTNP-EC phenotype of these individuals. These results highlight the important role of viral characteristics in the LTNP-EC clinical phenotype. These Env viral properties were common to all the cluster viruses and thus support the heritability of the viral characteristics. HIV-1 long-term nonprogressor elite controller patients, due to their permanent control of viral replication, have been the object of numerous studies to identify the factors responsible for this clinical phenotype. In this work, we analyzed the viral characteristics of the envelopes of viruses from a phylogenetic cluster of LTNP-EC patients. These envelopes showed ineffective binding to CD4 and the subsequent signaling activity to modify actin/tubulin cytoskeletons, which result in low fusion and deficient entry and infection capacities. These Env viral characteristics could explain the nonprogressor clinical phenotype of these patients. In addition, these inefficient viral properties were present in all viruses of the cluster, supporting the heritability of the viral phenotype.status: publishe

Procesos Psicológicos Básicos - PS371 - 202101

Descripción: Procesos psicológicos básicos es un curso introductorio teórico y práctico de primer ciclo en donde el estudiante tendrá un primer contacto acerca de lo que significa la psicología como ciencia. Explorará aspectos biopsicosociales del comportamiento humano. El curso busca que el estudiante explique los procesos psicológicos básicos considerando cómo los factores biopsicosociales del desarrollo humano influyen en los fenómenos psicológicos, así también en los diversos ámbitos de la vida. Este manejo teórico básico es relevante para que todo profesional, comprenda el funcionamiento integrado del individuo y como interactúa con su entorno. Es por ello, que corresponde al nivel de logro 1 de la competencia específica de la carrera: fundamento teórico conceptual

Additional file 1: of The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation

Summary illustration. Model for HDAC6-mediated A3G protection and control of HIV-1 infectiveness. HDAC6 directly interacts and forms a constitutive complex with A3G. This HDAC6/A3G complex is formed either in the absence (1) or in the presence of the HIV-1 Vif protein (2), and appears to be independent on the BUZ domain of HDAC6 (the different domains of HDAC6 are represented). Moreover, HDAC6 could concomitantly interact with Vif (3). The balance between the level of HDAC6 and Vif expression conditions the efficiency of HDAC6 to interact with A3G (1 and 2) and/or Vif (3 or 4; in the absence or presence of A3G, respectively), to avoid A3G-Vif interaction and subsequent Vif-mediated A3G ubiquitination and proteasome degradation (promoting HIV-1 infection) (pathway 5; the Vif-recruited E3 ligase complex (Vif-[CBF-β-EloB-EloC-Cul5-Rbx2/E2]) that targets A3G is shown). In fact, HDAC6 induces Vif autophagic clearance in a BUZ-dependent manner (pathway 3), thereby inhibiting HIV-1 infectiveness. This event is dependent on the HDAC6-deacetylase activity and could be blocked by the 3-MA inhibitor (6), which perturbs membrane flux during autophagosome formation; a process promoted early on by HDAC6 during autophagy. Hence, HDAC6 competes for the Vif-A3G interaction and subsequent anti-A3G functions (avoiding pathway 5). HDAC6 accounts for A3G steady-state expression level, stabilizing Vif-non-targeted forms of A3G (1). By these mechanisms, HDAC6 impairs HIV-1 infectiveness by Vif clearance (pathway 6) and/or favouring A3G-mediated anti-HIV-1 functions (pathway 1). Therefore, HDAC6/A3G appears as a new natural restriction complex acting against Vif function and HIV-1 infection