keyword
https://read.qxmd.com/read/38426331/hiresist-a-database-of-hiv-1-resistance-to-broadly-neutralizing-antibodies
#21
JOURNAL ARTICLE
Milind Misra, Jeffy Jeffy, Charis Liao, Stephanie Pickthorn, Kshitij Wagh, Alon Herschhorn
MOTIVATION: Changing the course of the human immunodeficiency virus type I (HIV-1) pandemic is a high public health priority with approximately 39 million people currently living with HIV-1 (PLWH) and about 1.5 million new infections annually worldwide. Broadly neutralizing antibodies (bnAbs) typically target highly conserved sites on the HIV-1 envelope glycoproteins (Envs), which mediate viral entry, and block the infection of diverse HIV-1 strains. But different mechanisms of HIV-1 resistance to bnAbs prevent robust application of bnAbs for therapeutic and preventive interventions...
February 29, 2024: Bioinformatics
https://read.qxmd.com/read/38422171/the-timing-of-hiv-1-infection-of-cells-that-persist-on-therapy-is-not-strongly-influenced-by-replication-competency-or-cellular-tropism-of-the-provirus
#22
JOURNAL ARTICLE
Sarah B Joseph, Melissa-Rose Abrahams, Matthew Moeser, Lynn Tyers, Nancie M Archin, Olivia D Council, Amy Sondgeroth, Ean Spielvogel, Ann Emery, Shuntai Zhou, Deelan Doolabh, Sherazaan D Ismail, Salim Abdool Karim, David M Margolis, Sergei Kosakovsky Pond, Nigel Garrett, Ronald Swanstrom, Carolyn Williamson
People with HIV-1 (PWH) on antiretroviral therapy (ART) can maintain undetectable virus levels, but a small pool of infected cells persists. This pool is largely comprised of defective proviruses that may produce HIV-1 proteins but are incapable of making infectious virus, with only a fraction (~10%) of these cells harboring intact viral genomes, some of which produce infectious virus following ex vivo stimulation (i.e. inducible intact proviruses). A majority of the inducible proviruses that persist on ART are formed near the time of therapy initiation...
February 29, 2024: PLoS Pathogens
https://read.qxmd.com/read/38405717/-in-vivo-affinity-maturation-of-the-hiv-1-env-binding-domain-of-cd4
#23
Andi Pan, Charles C Bailey, Tianling Ou, Jinge Xu, Xin Liu, Baodan Hu, Gogce Crynen, Nickolas Skamangas, Naomi Bronkema, Mai Tran, Huihui Mu, Xia Zhang, Yiming Yin, Michael D Alpert, Wenhui He, Michael Farzan
Many human proteins have been repurposed as biologics for clinical use. These proteins have been engineered with in vitro techniques that improve affinity for their ligands. However, these approaches do not select against properties that impair efficacy such as protease sensitivity or self-reactivity. Here we engineer the B-cell receptor of primary murine B cells to express a human protein biologic without disrupting their ability to affinity mature. Specifically, CD4 domains 1 and 2 (D1D2) of a half-life enhanced-HIV-1 entry inhibitor CD4-Ig (CD4-Ig-v0) were introduced into the heavy-chain loci of murine B cells, which were then adoptively transferred to wild-type mice...
February 9, 2024: Research Square
https://read.qxmd.com/read/38403541/association-of-lipoprotein-a-with-peri-coronary-inflammation-in-persons-with-and-without-hiv-infection
#24
JOURNAL ARTICLE
Erin Zisman, Mian Hossain, Nicholas T Funderburg, Robert Christenson, Jean Jeudy, Shana Burrowes, Allison G Hays, Nivya George, Michael L Freeman, Heather Rebuck, Sarah E Mitchell, Michael Miller, Shashwatee Bagchi
BACKGROUND: Persons with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD) compared to persons without HIV (PWoH). Lipoprotein a (Lp(a)) is a known atherosclerotic risk factor in PWoH, but there are no studies investigating Lp(a) and peri-coronary inflammation. OBJECTIVE: To investigate whether Lp(a) is associated with peri-coronary inflammation as assessed by the fat attenuation index (FAI) and activated monocytes and T lymphocytes in PWH and PWoH...
February 15, 2024: Journal of Clinical Lipidology
https://read.qxmd.com/read/38398205/transduction-efficiency-of-zika-virus-e-protein-pseudotyped-hiv-1-gfp-and-its-oncolytic-activity-tested-in-primary-glioblastoma-cell-cultures
#25
JOURNAL ARTICLE
Jan Patrick Formanski, Hai Dang Ngo, Vivien Grunwald, Celine Pöhlking, Jana Sue Jonas, Dominik Wohlers, Birco Schwalbe, Michael Schreiber
The development of new tools against glioblastoma multiforme (GBM), the most aggressive and common cancer originating in the brain, remains of utmost importance. Lentiviral vectors (LVs) are among the tools of future concepts, and pseudotyping offers the possibility of tailoring LVs to efficiently transduce and inactivate GBM tumor cells. Zika virus (ZIKV) has a specificity for GBM cells, leaving healthy brain cells unharmed, which makes it a prime candidate for the development of LVs with a ZIKV coat. Here, primary GBM cell cultures were transduced with different LVs encased with ZIKV envelope variants...
February 17, 2024: Cancers
https://read.qxmd.com/read/38370774/-in-vivo-affinity-maturation-of-the-hiv-1-env-binding-domain-of-cd4
#26
Andi Pan, Charles C Bailey, Tianling Ou, Jinge Xu, Xin Liu, Baodan Hu, Gogce Crynen, Nickolas Skamangas, Naomi Bronkema, Mai Tran, Huihui Mu, Xia Zhang, Yiming Yin, Michael D Alpert, Wenhui He, Michael Farzan
Many human proteins have been repurposed as biologics for clinical use. These proteins have been engineered with in vitro techniques that improve affinity for their ligands. However, these approaches do not select against properties that impair efficacy such as protease sensitivity or self-reactivity. Here we engineer the B-cell receptor of primary murine B cells to express a human protein biologic without disrupting their ability to affinity mature. Specifically, CD4 domains 1 and 2 (D1D2) of a half-life enhanced-HIV-1 entry inhibitor CD4-Ig (CD4-Ig-v0) were introduced into the heavy-chain loci of murine B cells, which were then adoptively transferred to wild-type mice...
February 5, 2024: bioRxiv
https://read.qxmd.com/read/38369811/optimal-control-of-a-multi-scale-hiv-opioid-model
#27
JOURNAL ARTICLE
Eric Numfor, Necibe Tuncer, Maia Martcheva
In this study, we apply optimal control theory to an immuno-epidemiological model of HIV and opioid epidemics. For the multi-scale model, we used four controls: treating the opioid use, reducing HIV risk behaviour among opioid users, entry inhibiting antiviral therapy, and antiviral therapy which blocks the viral production. Two population-level controls are combined with two within-host-level controls. We prove the existence and uniqueness of an optimal control quadruple. Comparing the two population-level controls, we find that reducing the HIV risk of opioid users has a stronger impact on the population who is both HIV-infected and opioid-dependent than treating the opioid disorder...
December 2024: Journal of Biological Dynamics
https://read.qxmd.com/read/38369246/neutralizing-antibodies-to-block-viral-entry-and-for-identification-of-entry-inhibitors
#28
REVIEW
Ee Hong Tam, Yu Peng, Megan Xin Yan Cheah, Chuan Yan, Tianshu Xiao
Neutralizing antibodies (NAbs) are naturally produced by our immune system to combat viral infections. Clinically, neutralizing antibodies with potent efficacy and high specificity have been extensively used to prevent and treat a wide variety of viral infections, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), Dengue Virus (DENV) and Hepatitis B Virus (HBV). An overwhelmingly large subset of clinically effective NAbs operates by targeting viral envelope proteins to inhibit viral entry into the host cell...
February 17, 2024: Antiviral Research
https://read.qxmd.com/read/38364308/glycan-modified-peptides-for-dual-inhibition-of-human-immunodeficiency-virus-entry-into-dendritic-cells-and-t-cells
#29
JOURNAL ARTICLE
Shuihong Cheng, Mingli Li, Yong Feng, Tong Liu, Lin He, Mingyue Xu, Liying Ma, Xuebing Li
Dendritic cells (DCs) play a crucial role in HIV-1 infection of CD4+ T cells. DC-SIGN, a lectin expressed on the surface of DCs, binds to the highly mannosylated viral membrane protein gp120 to capture HIV-1 virions and then transport them to target T cells. In this study, we modified peptide C34, an HIV-1 fusion inhibitor, at different sites using different sizes of the DC-SIGN-specific carbohydrates to provide dual-targeted HIV inhibition. The dual-target binding was confirmed by mechanistic studies. Pentamannose-modified C34 inhibited virus entry into both DC-SIGN+ 293T cells (52%-71% inhibition at 500 μM) and CD4+ TZM-b1 cells (EC50 = 0...
February 16, 2024: Journal of Medicinal Chemistry
https://read.qxmd.com/read/38363761/molecular-network-analysis-of-308-newly-diagnosed-hiv-infection-and-210-art-failure-patients-from-rural-counties-in-sichuan
#30
JOURNAL ARTICLE
Xia Zhong, Dan Yuan, Shuang Feng Fan, Yang Liu, Ling Su, Shi Jiao He, Shu Liang, Yi Yang
BACKGROUND: Few studies on molecular epidemiology have studied people with newly diagnosed HIV infection and ART Failure Patients at the same time in rural China. With more serious HIV epidemic than in other provinces in China, Sichuan is an area suitable for this study. OBJECTIVE: To analyze the characteristics of HIV-1 molecular networks and factors related to network entry among newly diagnosed HIV infection and ART Failure Patients in three county-level cities (A, B, C) in Sichuan Province, to provide scientific basis for accurate prevention and control...
2024: PloS One
https://read.qxmd.com/read/38361989/long-term-efficacy-and-safety-of-a-treatment-strategy-for-hiv-infection-using-protease-inhibitor-monotherapy-8-year-routine-clinical-care-follow-up-from-a-randomised-controlled-open-label-pragmatic-trial-pivot
#31
JOURNAL ARTICLE
Nicholas I Paton, Wolfgang Stöhr, Alejandro Arenas-Pinto, Amanda Clarke, Ian Williams, Margaret Johnson, Chloe Orkin, Fabian Chen, Vincent Lee, Alan Winston, Mark Gompels, Julie Fox, Karen Sanders, David T Dunn
BACKGROUND: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. METHODS: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded...
March 2024: EClinicalMedicine
https://read.qxmd.com/read/38361170/association-between-substance-abuse-and-mental-illness-symptoms-screener-samiss-scores-and-hiv-care-continuum-outcomes-in-people-newly-diagnosed-with-hiv-in-the-us-south
#32
JOURNAL ARTICLE
Manal Ahmed, Ank E Nijhawan, Ang Gao, Chul Ahn, Jeremy Y Chow
Mental illness (MI) and substance use (SU) are highly prevalent among people with HIV (PWH) and impact care outcomes. The Substance Abuse and Mental Illness Symptoms Screener (SAMISS) is a validated screener for MI and SU, but it is unknown how screening results at entry to care correlate with subsequent HIV outcomes. This is a retrospective chart review of individuals newly diagnosed with HIV between 2016 and 2019 in a Southern US, safety-net clinic. Baseline demographics, HIV risk factors, socioeconomic variables, and SAMISS screening scores were collected...
February 16, 2024: AIDS and Behavior
https://read.qxmd.com/read/38354195/socioeconomic-inequality-in-adults-undertaking-hiv-testing-over-time-in-ethiopia-based-on-data-from-demographic-and-health-surveys
#33
JOURNAL ARTICLE
Aklilu Endalamaw, Charles F Gilks, Yibeltal Assefa
INTRODUCTION: HIV testing is the entry point to HIV prevention, care and treatment and needs continuous evaluation to understand whether all social groups have accessed services equally. Addressing disparities in HIV testing between social groups results in effective and efficient response against HIV prevention. Despite these benefits, there was no previous study on inequality and determinants over time in Ethiopia. Thus, the objective of this research was to examine socioeconomic inequality in individuals undertaking HIV testing over time, allowing for the identification of persistent and emerging determinants...
2024: PloS One
https://read.qxmd.com/read/38342567/synthesis-and-anti-hiv-activities-of-phorbol-derivatives
#34
JOURNAL ARTICLE
Xiaolei Huang, Chengrun Tang, Xusheng Huang, Yun Yang, Qirun Li, Mengdi Ma, Lei Zhao, Liumeng Yang, Yadong Cui, Zhenqing Zhang, Yongtang Zheng, Jian Zhang
In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC50 2...
February 2024: Chinese Journal of Natural Medicines
https://read.qxmd.com/read/38328121/chikungunya-virus-release-is-reduced-by-tim-1-receptors-through-binding-of-envelope-phosphatidylserine
#35
Judith M Reyes Ballista, Ashley J Hoover, Joseph T Noble, Marissa D Acciani, Kerri L Miazgowicz, Sarah A Harrison, Grace Andrea L Tabscott, Avery Duncan, Don N Barnes, Ariana R Jimenez, Melinda A Brindley
UNLABELLED: T-cell immunoglobin and mucin domain protein-1 (TIM-1) mediates entry of Chikungunya virus (CHIKV) into some mammalian cells through the interaction with envelope phospholipids. While this interaction enhances entry, TIM has been shown to tether newly formed HIV and Ebola virus particles, limiting their efficient release. In this study, we investigate the ability of surface receptors such as TIM-1 to sequester newly budded virions on the surface of infected cells. We established a luminescence reporter system to produce Chikungunya viral particles that integrate nano-luciferase and easily quantify viral particles...
January 26, 2024: bioRxiv
https://read.qxmd.com/read/38328062/high-resolution-inference-of-multiplexed-anti-hiv-gene-editing-using-single-cell-targeted-dna-sequencing
#36
Mohamed S Bouzidi, Zain Y Dossani, Carolina Di Benedetto, Kyle A Raymond, Shivani Desai, Leonard R Chavez, Paola Betancur, Satish K Pillai
UNLABELLED: Gene therapy-based HIV cure strategies typically aim to excise the HIV provirus directly, or target host dependency factors (HDFs) that support viral persistence. Cure approaches will likely require simultaneous co-targeting of multiple sites within the HIV genome to prevent evolution of resistance, and/or co-targeting of multiple HDFs to fully render host cells refractory to HIV infection. Bulk cell-based methods do not enable inference of co-editing within individual viral or target cell genomes, and do not discriminate between monoallelic and biallelic gene disruption...
January 24, 2024: bioRxiv
https://read.qxmd.com/read/38307098/safety-of-teropavimab-and-zinlirvimab-with-lenacapavir-once-every-6-months-for-hiv-treatment-a-phase-1b-randomised-proof-of-concept-study
#37
RANDOMIZED CONTROLLED TRIAL
Joseph J Eron, Susan J Little, Gordon Crofoot, Paul Cook, Peter J Ruane, Dushyantha Jayaweera, Laurie A VanderVeen, Edwin DeJesus, Yanan Zheng, Anthony Mills, Hailin Huang, Sarah E Waldman, Moti Ramgopal, Linda Gorgos, Sean E Collins, Jared M Baeten, Marina Caskey
BACKGROUND: Long-acting treatment for HIV has potential to improve adherence, provide durable viral suppression, and have long-term individual and public health benefits. We evaluated treatment with two antibodies that broadly and potently neutralise HIV (broadly neutralising antibodies; bNAbs), combined with lenacapavir, a long-acting capsid inhibitor, as a long-acting regimen. METHODS: This ongoing, randomised, blind, phase 1b proof-of-concept study conducted at 11 HIV treatment centres in the USA included adults with a plasma HIV-1 RNA concentration below 50 copies per mL who had at least 18 months on oral antiretroviral therapy (ART), CD4 counts of at least 500 cells per μL, and protocol-defined susceptibility to bNAbs teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS)...
March 2024: Lancet HIV
https://read.qxmd.com/read/38306387/implementing-ecological-momentary-assessments-to-measure-violence-and-adolescent-hiv-transmission-risk-lessons-from-johannesburg-south-africa
#38
JOURNAL ARTICLE
Janan Janine Dietrich, Stefanie Hornschuh, Phumla Madi, Candice W Ramsammy, Lerato Tsotetsi, Gugulethu Tshabalala, Busisiwe Nkala-Dlamini, Avy Violari, Rachel Kidman
Ecological Momentary Assessment (EMA) is an important methodology to understand risky behaviour and holds promise for HIV research. EMA is still novel in sub-Saharan Africa. We describe challenges and lessons learned on a novel study implementing mobile phone EMAs with adolescent boys in South Africa. The Tsamaisano study was a longitudinal study from 2020-2023 to recruit adolescent boys aged 15-19 years; including those without HIV and those perinatally infected and living with HIV. Participants were prompted to complete 52 weekly mobile phone survey on emotional state, exposure to and perpetration of violence, and sexual risk behaviour...
February 2024: PLOS Digit Health
https://read.qxmd.com/read/38289101/inhibition-of-human-immunodeficiency-virus-hiv-1-infectivity-by-expression-of-poorly-or-broadly-neutralizing-antibodies-against-env-in-virus-producing-cells
#39
JOURNAL ARTICLE
Qian Wang, Shijian Zhang, Hanh T Nguyen, Joseph Sodroski
The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein precursor (gp160) trimerizes, is modified by high-mannose glycans in the endoplasmic reticulum, and is transported via Golgi and non-Golgi secretory pathways to the infected cell surface. In the Golgi, gp160 is partially modified by complex carbohydrates and proteolytically cleaved to produce the mature functional Env trimer, which is preferentially incorporated into virions. Broadly neutralizing antibodies (bNAbs) generally recognize the cleaved Env trimer, whereas poorly neutralizing antibodies (pNAbs) bind the conformationally flexible gp160...
January 30, 2024: Journal of Virology
https://read.qxmd.com/read/38267583/hiv-1-capsids-enter-the-fg-phase-of-nuclear-pores-like-a-transport-receptor
#40
JOURNAL ARTICLE
Liran Fu, Erika N Weiskopf, Onno Akkermans, Nicholas A Swanson, Shiya Cheng, Thomas U Schwartz, Dirk Görlich
HIV-1 infection requires nuclear entry of the viral genome. Previous evidence suggests that this entry proceeds through nuclear pore complexes (NPCs), with the 120 × 60 nm capsid squeezing through an approximately 60-nm-wide central channel1 and crossing the permeability barrier of the NPC. This barrier can be described as an FG phase2 that is assembled from cohesively interacting phenylalanine-glycine (FG) repeats3 and is selectively permeable to cargo captured by nuclear transport receptors (NTRs)...
January 24, 2024: Nature
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