human immunodeficiency virus
Research Article | Therapeutics and PreventionCD4+ T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through AutophagyHIV-1 is a major global health challenge. The development of an effective vaccine and/or a therapeutic cure is a top priority. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 hinders this progress. Here we developed an approach using nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP). Not only do TNP effectively...
Research Article | Host-Microbe BiologyHIV Vpr Modulates the Host DNA Damage Response at Two Independent Steps to Damage DNA and Repress Double-Strand DNA Break RepairThe DNA damage response (DDR) is a signaling cascade that safeguards the genome from genotoxic agents, including human pathogens. However, the DDR has also been utilized by many pathogens, such as human immunodeficiency virus (HIV), to enhance infection. To properly treat HIV-positive individuals, we must understand how the virus usurps our own cellular processes. Here, we have found that an important yet poorly understood gene in HIV,...
Research Article | Therapeutics and PreventionRecognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine TrialAntibody-dependent cellular cytotoxicity (ADCC) correlated with a reduced risk of infection from HIV-1 in the RV144 vaccine trial, the only HIV-1 vaccine trial to date to show any efficacy. Antibodies specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (cluster A region) were induced in the RV144 trial and their ADCC activities were implicated in the vaccine efficacy. We present structural analyses of the...
Editor's Pick Research Article | Host-Microbe BiologyReversal of Epigenetic Silencing Allows Robust HIV-1 Replication in the Absence of Integrase FunctionWhile retroviral DNA is synthesized normally after infection by integrase-deficient viruses, the resultant episomal DNA is then epigenetically silenced. Here, we show that expression of the Tax transcription factor encoded by a second human retrovirus, HTLV-1, prevents or reverses the epigenetic silencing of unintegrated HIV-1 DNA and instead induces the addition of activating epigenetic marks and the recruitment of NF-κB/Rel proteins...
Commentary | Host-Microbe BiologyDecreased, Deformed, Defective—How HIV-1 Vpu Targets PeroxisomesPeroxisomes are found in essentially all eukaryotic cells and have been described as important hubs in innate sensing and the induction of type III interferons upon viral infection. Nevertheless, it remains poorly investigated how viral pathogens modulate biogenesis or function of peroxisomes to evade innate sensing and restriction. In a recent study, Hobman and colleagues found that the accessory viral protein u (Vpu) of HIV-1 inhibits...
Research Article | Therapeutics and PreventionGlycerol Monolaurate, an Analogue to a Factor Secreted by Lactobacillus, Is Virucidal against Enveloped Viruses, Including HIV-1A total of 340 million sexually transmitted infections (STIs) are acquired each year. Antimicrobial agents that target multiple infectious pathogens are ideal candidates to reduce the number of newly acquired STIs. The antimicrobial and immunoregulatory properties of GML make it an excellent candidate to fit this critical need. Previous studies established the safety profile and antibacterial activity of GML against both Gram-positive...
Research Article | Therapeutics and PreventionA Bispecific Antibody That Simultaneously Recognizes the V2- and V3-Glycan Epitopes of the HIV-1 Envelope Glycoprotein Is Broader and More Potent than Its Parental AntibodiesBroadly neutralizing antibodies (bNAbs) can prevent a new HIV-1 infection and can at least temporarily suppress an established infection. However, antibody-resistant viruses rapidly emerge in infected persons treated with any single bNAb. Several bispecific antibodies have been developed to increase the breadth of these antibodies, but typically only one arm of these bispecific constructs binds the HIV-1 envelope glycoprotein trimer (...
Research Article | Host-Microbe BiologyCpG Frequency in the 5′ Third of the env Gene Determines Sensitivity of Primary HIV-1 Strains to the Zinc-Finger Antiviral ProteinEvasion of the zinc-finger antiviral protein (ZAP) may drive CpG dinucleotide suppression in HIV-1 and many other viral pathogens but the viral determinants of ZAP sensitivity are poorly defined. Here, we examined CpG suppression and ZAP sensitivity in a large number of primate lentiviruses and demonstrate that their genomic frequency of CpGs varies substantially and does not correlate with ZAP sensitivity. We further show that the...
Research Article | Host-Microbe BiologyCD71+ Erythroid Cells Exacerbate HIV-1 Susceptibility, Mediate trans-Infection, and Harbor Infective Viral ParticlesImmature red blood cells (erythroid precursors or CD71+ erythroid cells) have a wide range of immunomodulatory properties. In this study, we found that these erythroid precursors are abundant in the human cord blood/placental tissues, in the blood of HIV-infected and anemic individuals. We observed that these cells exacerbate HIV-1 replication/infection in target cells and even make HIV target cells more permissible to HIV...
Research Article | Molecular Biology and PhysiologyTREM-1 Protects HIV-1-Infected Macrophages from Apoptosis through Maintenance of Mitochondrial FunctionThe major challenge to human immunodeficiency virus (HIV) treatment is the development of strategies that lead to viral eradication. A roadblock to accomplishing this goal is the lack of an approach that would safely eliminate HIV from all resting/latent reservoirs, including macrophages. Macrophages are a key part of the innate immune system and are responsible for recognizing invading microbes and sending appropriate signals to other...