Global dynamics of a class of HIV-1 infection models with latently infected cells

2015 ◽  
Vol 20 (1) ◽  
pp. 21-37 ◽  
Author(s):  
Haibin Wang ◽  
◽  
Rui Xu ◽  
Zhaowei Wang ◽  
Hui Chen
Keyword(s):  
Global Dynamics ◽  
Infection Models ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Induction of Autophagy to Achieve a Human Immunodeficiency Virus Type 1 Cure

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1798
Author(s):  
Grant R. Campbell ◽  
Stephen A. Spector
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Functional Cure ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

Effective antiretroviral therapy has led to significant human immunodeficiency virus type 1 (HIV-1) suppression and improvement in immune function. However, the persistence of integrated proviral DNA in latently infected reservoir cells, which drive viral rebound post-interruption of antiretroviral therapy, remains the major roadblock to a cure. Therefore, the targeted elimination or permanent silencing of this latently infected reservoir is a major focus of HIV-1 research. The most studied approach in the development of a cure is the activation of HIV-1 expression to expose latently infected cells for immune clearance while inducing HIV-1 cytotoxicity—the “kick and kill” approach. However, the complex and highly heterogeneous nature of the latent reservoir, combined with the failure of clinical trials to reduce the reservoir size casts doubt on the feasibility of this approach. This concern that total elimination of HIV-1 from the body may not be possible has led to increased emphasis on a “functional cure” where the virus remains but is unable to reactivate which presents the challenge of permanently silencing transcription of HIV-1 for prolonged drug-free remission—a “block and lock” approach. In this review, we discuss the interaction of HIV-1 and autophagy, and the exploitation of autophagy to kill selectively HIV-1 latently infected cells as part of a cure strategy. The cure strategy proposed has the advantage of significantly decreasing the size of the HIV-1 reservoir that can contribute to a functional cure and when optimised has the potential to eradicate completely HIV-1.

Galectin-3 is involved in HIV-1 expression through NF-κB activation and associated with Tat in latently infected cells

2019 ◽  
Vol 260 ◽  
pp. 86-93 ◽  
Author(s):  
Mika Okamoto ◽  
Akemi Hidaka ◽  
Masaaki Toyama ◽  
Masanori Baba
Keyword(s):  
Latently Infected ◽  
Galectin 3 ◽  
Infected Cells ◽  
Hiv 1

scholarly journals The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94104-94116 ◽  
Author(s):  
Hanyu Pan ◽  
Panpan Lu ◽  
Yinzhong Shen ◽  
Yanan Wang ◽  
Zhengtao Jiang ◽  
...  
Keyword(s):  
Latently Infected ◽  
Infected Cells ◽  
Latent Hiv ◽  
Hiv 1

scholarly journals HIV-1 DNA predicts disease progression and post-treatment virological control

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
James P Williams ◽  
Jacob Hurst ◽  
Wolfgang Stöhr ◽  
Nicola Robinson ◽  
Helen Brown ◽  
...  
Keyword(s):  
Disease Progression ◽  
Treatment Interruption ◽  
Viral Rebound ◽  
Clinical Progression ◽  
Clinical Trial Registration ◽  
Plasma Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Multivariable Analyses ◽  
Hiv 1

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20

A new small-molecule compound, Q308, silences latent HIV-1 provirus by suppressing Tat- and FACT-mediated transcription

2021 ◽  
Author(s):  
Chen-liang Zhou ◽  
Yi-fan Huang ◽  
Yi-bin Li ◽  
Tai-zhen Liang ◽  
Teng-yi Zheng ◽  
...  
Keyword(s):  
Small Molecule ◽  
Difficult Problem ◽  
Viral Reservoir ◽  
Functional Cure ◽  
Latently Infected ◽  
Small Molecule Compound ◽  
Infected Cells ◽  
Latent Hiv ◽  
Anti Hiv ◽  
Hiv 1

Eliminating the latent HIV reservoir remains a difficult problem for creating an HIV functional cure or achieving remission. The “block-and-lock” strategy aims to steadily suppress transcription of the viral reservoir and lock the HIV promoter in deep latency using latency-promoting agents (LPAs). However, to date, most of the investigated LPA candidates are not available for clinical trials, and some of them exhibit immune-related adverse reactions. The discovery and development of new, active, and safe LPA candidates for an HIV cure are necessary to eliminate residual HIV-1 viremia through the “block-and-lock” strategy. In this study, we demonstrated that a new small-molecule compound, Q308, silenced the HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulating the expression levels of the facilitated chromatin transcription (FACT) complex. Strikingly, Q308 induced the preferential apoptosis in HIV-1 latently infected cells, indicating that Q308 may reduce the size of the viral reservoir and thus further prevent viral rebound. These findings highlight that Q308 is a novel and safe anti-HIV-1 inhibitor candidate for a functional cure.

scholarly journals Similar frequency and inducibility of intact HIV-1 proviruses in blood and lymph nodes

2020 ◽  
Author(s):  
Alyssa R Martin ◽  
Alexandra M Bender ◽  
Jada Hackman ◽  
Kyungyoon J Kwon ◽  
Briana A Lynch ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Viral Rna ◽  
Latent Reservoir ◽  
Similar Frequency ◽  
Latently Infected ◽  
Infected Cells ◽  
Secondary Lymphoid Organs ◽  
Hiv 1

Abstract Background The HIV-1 latent reservoir (LR) in resting CD4 + T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes. Methods We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from ten HIV-1-infected patients on ART using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay. Results The frequencies of CD4 + T cells with intact proviruses were not significantly different in PB vs LN (61vs104/10 6CD4 + cells), and were substantially lower than frequencies of CD4 + T cells with defective proviruses. The frequencies of CD4 + T cells induced to produce high levels of viral RNA were not significantly different in PB vs LN (4.3/10 6 vs 7.9/10 6), but were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses revealed comparable sequences in paired PB and LN samples. Conclusions These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs

scholarly journals eCD4-Ig Variants That More Potently Neutralize HIV-1

2018 ◽  
Vol 92 (12) ◽  
Author(s):  
Ina Fetzer ◽  
Matthew R. Gardner ◽  
Meredith E. Davis-Gardner ◽  
Neha R. Prasad ◽  
Barnett Alfant ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Entry Inhibitor ◽  
Immune Effector ◽  
Effector Cells ◽  
Antibody Recognition ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Prophylaxis Therapy ◽  
Hiv 1

ABSTRACTThe human immunodeficiency virus type 1 (HIV-1) entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralized all HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates that it has been tested against, suggesting that it may be useful in clinical settings, where antibody escape is a concern. Here, we characterize three new eCD4-Ig variants, each with a different architecture and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as the original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented the promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications.IMPORTANCEHIV-1 bNAbs have properties different from those of antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral life cycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the utility of antibodies as a treatment for HIV-1 infection or as part of an effort to eradicate latently infected cells. eCD4-Ig is an antibody-like entry inhibitor that closely mimics HIV-1's obligate receptors. eCD4-Ig appears to be qualitatively different from antibodies, since it neutralizes all HIV-1, HIV-2, and SIV isolates. Here, we characterize three new structurally distinct eCD4-Ig variants and show that each excels in a key property useful to prevent, treat, or cure an HIV-1 infection. For example, one variant neutralized HIV-1 most efficiently, while others best enlisted natural killer cells to eliminate infected cells. These observations will help generate eCD4-Ig variants optimized for different clinical applications.

scholarly journals Immunological and pharmacological strategies to reactivate HIV-1 from latently infected cells: a possibility for HIV-1 paediatric patients?

2015 ◽  
Vol 1 (3) ◽  
pp. 148-152 ◽  
Author(s):  
M. Martínez-Bonet ◽  
M.I. Clemente ◽  
M.J. Serramía ◽  
S. Moreno ◽  
E. Muñoz ◽  
...  
Keyword(s):  
Paediatric Patients ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Global Properties of Latent Virus Dynamics Models with Immune Impairment and Two Routes of Infection

2019 ◽  
Vol 8 (2) ◽  
pp. 16
Author(s):  
Aeshah A. Raezah ◽  
Ahmed M. Elaiw ◽  
Badria S. Alofi
Keyword(s):  
Global Stability ◽  
Lyapunov Method ◽  
Incidence Rates ◽  
Steady States ◽  
Global Properties ◽  
Infection Models ◽  
Latently Infected ◽  
Immune Impairment ◽  
Infected Cells ◽  
Dynamics Models

This paper studies the global stability of viral infection models with CTL immune impairment. We incorporate both productively and latently infected cells. The models integrate two routes of transmission, cell-to-cell and virus-to-cell. In the second model, saturated virus–cell and cell–cell incidence rates are considered. The basic reproduction number is derived and two steady states are calculated. We first establish the nonnegativity and boundedness of the solutions of the system, then we investigate the global stability of the steady states. We utilize the Lyapunov method to prove the global stability of the two steady states. We support our theorems by numerical simulations.

scholarly journals R88-APOBEC3Gm Inhibits the Replication of Both Drug-resistant Strains of HIV-1 and Viruses Produced From Latently Infected Cells

2014 ◽  
Vol 3 ◽  
pp. e151 ◽  
Author(s):  
Xiaoxia Wang ◽  
Zhujun Ao ◽  
Kallesh Danappa Jayappa ◽  
Bei Shi ◽  
Gary Kobinger ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Latently Infected ◽  
Infected Cells ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Hiv 1
Sign in / Sign up

Export Citation Format

Share Document