RESUMEN
The brain is a target of HIV-1 and serves as an important viral reservoir. Astrocytes, the most abundant glial cell in the human brain, are involved in brain plasticity and neuroprotection. Several studies have reported HIV-1 infection of astrocytes in cell cultures and infected brain tissues. The prevailing concept is that HIV-1 infection of astrocytes leads to latent infection. Here, we provide our perspective on endocytosis-mediated HIV-1 entry and its fate in astrocytes. Natural entry of HIV-1 into astrocytes occurs via endocytosis. However, endocytosis of HIV-1 in astrocytes is a natural death trap where the majority of virus particles are degraded in endosomes and a few which escape intact lead to successful infection. Thus, regardless of artificial fine-tuning (treatment with cytokines or proinflammatory products) done to astrocytes, HIV-1 does not infect them efficiently unless the viral entry route or the endosomal enzymatic machinery has been manipulated.
Asunto(s)
Astrocitos/virología , Encéfalo/virología , Endocitosis/fisiología , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Animales , Astrocitos/metabolismo , Técnicas de Cocultivo/métodos , HumanosRESUMEN
Pathogenic viruses have developed a molecular defense arsenal for their survival by counteracting the host anti-viral system known as RNA interference (RNAi). Cellular RNAi, in addition to regulating gene expression through microRNAs, also serves as a barrier against invasive foreign nucleic acids. RNAi is conserved across the biological species, including plants, animals and invertebrates. Viruses in turn, have evolved mechanisms that can counteract this anti-viral defense of the host. Recent studies of mammalian viruses exhibiting RNA silencing suppressor (RSS) activity have further advanced our understanding of RNAi in terms of host-virus interactions. Viral proteins and non-coding viral RNAs can inhibit the RNAi (miRNA/siRNA) pathway through different mechanisms. Mammalian viruses having dsRNA-binding regions and GW/WG motifs appear to have a high chance of conferring RSS activity. Although, RSSs of plant and invertebrate viruses have been well characterized, mammalian viral RSSs still need in-depth investigations to present the concrete evidences supporting their RNAi ablation characteristics. The information presented in this review together with any perspective research should help to predict and identify the RSS activity-endowed new viral proteins that could be the potential targets for designing novel anti-viral therapeutics.
Asunto(s)
Regulación Viral de la Expresión Génica , Interacciones Huésped-Patógeno , Interferencia de ARN , ARN Viral/metabolismo , Factores de Virulencia/metabolismo , Virus/inmunología , Virus/patogenicidad , Animales , Plantas , ARN no Traducido/metabolismo , Proteínas Virales/metabolismo , VirulenciaRESUMEN
Protein transduction with cell penetrating peptides over the past several years has been shown to be an effective way of delivering proteins in vitro and now several reports have also shown valuable in vivo applications in correcting disease states. An impressive bioinspired phenomenon of crossing biological barriers came from HIV transactivator Tat protein. Specifically, the protein transduction domain of HIV Tat has been shown to be a potent pleiotropic peptide in protein delivery. Various approaches such as molecular modeling, arginine guanidinium head group structural strategy, multimerization of PTD sequence and phage display system have been applied for taming of the PTD. This has resulted in identification of PTD variants which are efficient in cell membrane penetration and cytoplasmic delivery. In spite of these state of the art technologies, the dilemma of low protein transduction efficiency and target specific delivery of PTD fusion proteins remains unsolved. Moreover, some misconceptions about PTD of Tat in the literature require considerations. We have assembled critical information on secretory, plasma membrane penetration and transcellular properties of Tat and PTD using molecular analysis and available experimental evidences.