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Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia.

BACKGROUND: The development of pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Besides, data from developing settings including Ethiopia is still limited. Therefore, this study was aimed to assess HIV-1 genetic diversity and PDR mutations among ART-naive recently diagnosed HIV-1 infected individuals in Addis Ababa, Ethiopia. METHODS: Institutional based cross-sectional study was conducted from June to December 2018 in Addis Ababa among ART-naive recently diagnosed individuals. Partial HIV-1 pol region covering the entire protease (PR)…

Structure-Based Identification of HIV-1 Nucleocapsid Protein Inhibitors Active against Wild-Type and Drug-Resistant HIV-1 Strains.

HIV/AIDS is still one of the leading causes of death worldwide. Current drugs that target the canonical steps of the HIV-1 life cycle are efficient in blocking viral replication but are unable to eradicate HIV-1 from infected patients. Moreover, drug resistance (DR) is often associated with the clinical use of these molecules, thus raising the need for novel drug candidates as well as novel putative drug targets. In this respect, pharmacological inhibition of the highly conserved and multifunctional nucleocapsid protein (NC) of HIV-1 is considered a promising alternative to current drugs, part…

Control of early HIV-1 infection associates with plasmacytoid dendritic cell-reactive opsonophagocytic IgG antibodies to HIV-1 p24.

OBJECTIVES: We have previously demonstrated that HIV-1 p24-specific plasmacytoid dendritic cell-reactive opsonophagocytic antibody (PROAb) responses associate with control of chronic HIV infection. Here, we examined whether HIV-1 p24-specific PROAbs associate with control of early HIV infection and their relationship with HIV-1 p24-specific IgG subclasses. METHODS: Plasma collected at 8 and 52 weeks following primary HIV-1 infection was obtained from antiretroviral therapy-naïve patients who were classified as 'good' (plasma HIV-1 RNA < 5000 copies/ml; n = 17) or 'poor' (HIV-1 RNA > 50 000 co…

Учредительная активация MAVS Inhibits ВИЧ-1 Оплодотворение через Interferon Secretion и ввод в действие факторов ограничения ВИЧ-1.

Известно, что интерферон типа I препятствует репродукции ВИЧ-1 за счет впрыскивания генных интерферонов (ИПГ), включая ряд факторов ограничения ВИЧ-1. Чтобы лучше понять интерферонально-посредованное ограничение ВИЧ-1, мы создали учредительно активную форму адаптационного белка MAVS. Учредительный MAVS образовался в результате слияния полной длины MAVS в усеченную форму белка вируса Эпштейн Барра LMP1 (ΔLMP1). Супернавигационный от ΔLMP1-MAVS трансформированные 293T клетки содержали высокие уровни интерферонов типа I и блокировали воспроизведение ВИЧ как в TZM-bl, так и в первичных человечески

Совпадение в аннотации оригинала
Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG), including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length…

Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients.

Epidemiologic studies suggest that cocaine abuse worsens HIV-1 disease progression. Increased viral load has been suggested to play a key role for the accelerated HIV disease among cocaine-abusing patients. The goal of this study was to investigate whether cocaine enhances proviral DNA integration as a mechanism to increase viral load. We infected CD4(+) T cells that are the primary targets of HIV-1 in vivo and treated the cells with physiologically relevant concentrations of cocaine (1 µM-100 µM). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated…

Cell activation and HIV-1 replication in unstimulated CD4+ T lymphocytes ingesting exosomes from cells expressing defective HIV-1.

BACKGROUND: A relevant burden of defective HIV-1 genomes populates PBMCs from HIV-1 infected patients, especially during HAART treatment. These viral genomes, although unable to codify for infectious viral particles, can express viral proteins which may affect functions of host cells as well as bystander ones. Cells expressing defective HIV-1 have a lifespan longer than that of cells producing infectious particles. Hence, their interaction with other cell types, including resting lymphocytes, is expected to occur frequently in tissues where HIV actively replicates. We investigated the effects …

Specific reactivation of latent HIV-1 with designer zinc-finger transcription factors targeting the HIV-1 5'-LTR promoter.

HIV-1 latency remains the primary obstacle to the eradication of this virus. The current latency-reversing agents cannot effectively and specifically eliminate latent HIV-1 reservoirs. Therefore, better approaches are urgently needed. In this study, we describe a novel strategy to reactivate latent HIV-1 using zinc-finger transcription factors composed of designer zinc-finger proteins and the transcriptional activation domain VP64. For the first time, we demonstrate that ZF-VP64 with HIV-1 long terminal repeat (LTR) promoter-specific affinity could significantly reactivate HIV-1 expression fro…

Cocaine enhances HIV-1-induced CD4(+) T-cell apoptosis: implications in disease progression in cocaine-abusing HIV-1 patients.

Substance abuse is a major barrier in eradication of the HIV epidemic because it serves as a powerful cofactor for viral transmission, disease progression, and AIDS-related mortality. Cocaine, one of the commonly abused drugs among HIV-1 patients, has been suggested to accelerate HIV disease progression. However, the underlying mechanism remains largely unknown. Therefore, we tested whether cocaine augments HIV-1-associated CD4(+) T-cell decline, a predictor of HIV disease progression. We examined apoptosis of resting CD4(+) T cells from HIV-1-negative and HIV-1-positive donors in our study, b…

Low levels of HIV-1 plasma viral load in patients infected with HIV-1 subtype b and advanced immunosuppression.

OBJECTIVES: Some HIV-1 infected patients show low levels of viraemia despite having advanced immunosuppression. Cases with falsely undetectable viraemia by conventional PCR have been reported when patients were infected with non-B subtypes. The aim of this study was to investigate whether this immunovirological discordance can be due to the presence of HIV-1 non-B subtypes, and whether a modified PCR procedure can yield different HIV viraemia values in these cases. METHODS: Fifteen HIV-infected patients either naive for antiretroviral drugs or under treatment, with HIV plasma viraemia below 1…

The gp120 Envelope Glycoprotein of HIV-1 Triggers Macropinocytosis in Primary CD4+ T Cells to Promote HIV-1 Infection.

Macropinocytosis is a large-scale, actin-driven, fluid-phase form of endocytosis that can be exploited by HIV-1 for entry into primary CD4+ T cells. Herein, we show that HIV-1 actively induces macropinocytosis in resting and activated primary CD4+ T cells. HIV-1-induced T cell macropinocytosis is triggered by the interaction of soluble gp120 Env with cell surface CD4, is clathrin-independent and actin-dependent, and does not require CXCR4 or any other known HIV-1 coreceptors. Notably, Env-induced macropinocytosis requires calcium-independent phospholipase A2 (iPLA2) activity, identifying a rol…

Analytical Agreement of the GeneXpert HIV-1 Viral Load Assay Compared with the Abbott Alinity m HIV-1 Assay.

Background/Objectives: Early and accurate quantification of Human Immunodeficiency Virus type 1 (HIV-1) viral load is essential for monitoring antiretroviral therapy and guiding clinical management. Although conventional real-time polymerase chain reaction (PCR) platforms provide reliable viral load measurement, they often require centralized laboratories and longer turnaround times. Cartridge-based systems such as the GeneXpert HIV-1 Viral Load assay offer a simplified testing workflow and may facilitate decentralized molecular testing. This study aimed to evaluate the qualitative and quantit…

YAP Inhibits HIV-1 transcription and promotes HIV-1 latency by regulating E3 ubiquitin ligase UHRF1 mediated tat degradation.

The latency of human immunodeficiency virus type 1 (HIV-1) is a major barrier to achieving an HIV-1 cure, as antiretroviral therapy does not target the latent virus. Virus-host interactions play an essential role in various stages of the HIV-1 lifecycle. Exploring the interaction between host factors and HIV-1 infection is critical for developing new HIV-1 treatment strategies. Yes-associated protein (YAP) is a key co-transcription factor in the Hippo signaling pathway, which regulates the occurrence and development of various diseases, including cellular metabolism, cancer, immunity, and vira…

Blocking Host Factors IAP and DDX3 Activates HIV-1 Transcription and Increases Apoptosis Sensitivity of HIV-1 Infected Cells.

Antiretroviral therapy (ART) effectively suppresses HIV-1 replication but does not purge the latent HIV-1 reservoir. Strategies aimed at HIV-1 latency reversal and subsequent elimination of infected cells are being explored. Targeting the inhibitor of apoptosis proteins (IAP) and DEAD-box polypeptide 3 (DDX3) RNA helicase reduces the HIV-1 reservoir ex vivo. However, the mechanisms driving apoptosis of HIV-1 infected cells remain unclear. Here, we uncovered the mechanism regarding HIV-1 transcriptional activation and induction of apoptosis specific for HIV-1 infected cells using an acute in vi…

GRHAL1, a novel lncRNA, regulates HIV-1 gene expression by modulating Tat- and Sp1-mediated HIV-1 LTR activation.

We recently reported that GADD34, an integrated stress response (ISR)-associated protein expressed at low levels in many cell lines, functions as a novel HIV-1 restriction factor. To elucidate the mechanism underlying GADD34-mediated inhibition of HIV replication, we investigated the role of long non-coding RNAs (lncRNAs). Here, we identify and characterize a novel lncRNA, GRHAL1 (GADD34-regulated HIV accessory lncRNA-1), which is highly expressed in GADD34-knockout (GADD34-KO) cells relative to WT cells. GRHAL1 is expressed at low basal levels in Jurkat and MT-2 CD4+ T cell lines and in prima…

Identification of Multiple Unique HIV-1 Recombinant Forms in Newly Reported HIV-1 Infected Individuals - Anhui Province, China, 2023.

INTRODUCTION: The genetic diversity of human immunodeficiency virus-1 (HIV-1) in China is characterized by multiple subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs) across the country. Through timely molecular surveillance, over 65 distinct CRFs have been identified in China to date. In this study, we identified five novel URFs among newly reported HIV-1 infected individuals in Anhui Province, China. METHODS: Near-full length HIV genome sequences were obtained using two-half molecule amplification methods from five samples containing potential URFs. The seque…

The RNA-Binding Proteins SRP14 and HMGB3 Control HIV-1 Tat mRNA Processing and Translation During HIV-1 Latency.

HIV-1 Tat protein is essential for virus production. RNA-binding proteins that facilitate Tat production may be absent or downregulated in resting CD4+ T-cells, the main reservoir of latent HIV in people with HIV (PWH) on antiretroviral therapy (ART). In this study, we examined the role of Tat RNA-binding proteins on the expression of Tat and control of latent and productive infection. Affinity purification coupled with mass spectrometry analysis was used to detect binding partners of MS2-tagged tat mRNA in a T cell-line model of HIV latency. The effect of knockdown and overexpression of the p…

Baseline Investigation of HIV-1 Primary Drug Resistance Among Newly Diagnosed Treatment-Naïve HIV-1 Individuals in Hebei, China.

Human immunodeficiency virus (HIV) primary drug resistance (PDR) has influenced the long-term therapeutic effects of antiretroviral drugs. However, for the overall PDR prevalence in China, no report was found in published articles. In our study, an extensive cross-sectional investigation based on all newly diagnosed treatment-naive HIV-infected individuals was conducted. The overall prevalence of HIV-1 PDR among newly diagnosed treatment-naive HIV-1 individuals was 8.3% (60/720), obviously beyond the warning line (5.0%) set by WHO. The prevalence of PDR to PIs, nucleoside reverse transcriptase…

Circulation of HIV-1 Multiple Complexity Recombinant Forms Among Female Sex Workers Recently Infected with HIV-1 in Thailand.

The circulating subtype distribution of HIV-1 has not been well characterized in female sex worker (FSW) populations in Thailand. To understand the mechanisms and interrelationships of epidemics involving FSWs in Thailand, we performed a large molecular epidemiological study of FSWs aged 25 years with recently acquired HIV-1 infections. The samples were collected in 2005, 2007, 2009, and 2011 in 38 provinces, representing every region of Thailand. After gag (p24), pol (pro-RT), and env (C2/V3) were sequenced, comprehensive genome analysis was performed. Genetic subtypes were determined in 159 …

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4.

HIV-1 is the most prevalent retrovirus, with over 30 million people infected worldwide. Nevertheless, infection caused by other human retroviruses like HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4 is gaining importance. Initially confined to specific geographical areas, HIV-2, HTLV-1 and HTLV-2 are becoming a major concern in non-endemic countries due to international migration flows. Clinical manifestations of retroviruses range from asymptomatic carriers to life-threatening conditions, such as AIDS in HIV-2 infection or adult T-cell lymphoma/leukemia or tropical spastic paraparesis in HTLV-1 inf…

HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam.

BACKGROUND: Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. METHODS: We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance muta