scholarly journals Determination of Number of Infected Cells and Concentration of Viral Particles in Plasma during HIV-1 Infections Using Shehu Transformation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
M. Higazy ◽  
Sudhanshu Aggarwal ◽  
Y. S. Hamed
Keyword(s):  
Initial Conditions ◽  
Integral Transformation ◽  
Mathematical Representation ◽  
Infection Model ◽  
Viral Particles ◽  
Infected Cells ◽  
Linear Differential ◽  
The Mathematical Model ◽  
Ordinary Linear Differential Equations ◽  
Hiv 1

In this paper, the authors determine the number of infected cells and concentration of infected (viral) particles in plasma during HIV-1 (human immunodeficiency virus type one) infections using Shehu transformation. For this, the authors first defined some useful properties of Shehu transformation with proof and then applied Shehu transformation on the mathematical representation of the HIV-1 infection model. The mathematical model of HIV-1 infections contains a system of two simultaneous ordinary linear differential equations with initial conditions. Results depict that Shehu transformation is very effective integral transformation for determining the number of infected cells and concentration of viral particles in plasma during HIV-1 infections.

scholarly journals Flow Cytometry Analysis of HIV-1 Env Conformations at the Surface of Infected Cells and Virions: Role of Nef, CD4, and SERINC5

2019 ◽  
Vol 94 (6) ◽  
Author(s):  
Isabelle Staropoli ◽  
Jérémy Dufloo ◽  
Anaïs Ducher ◽  
Pierre-Henri Commere ◽  
Anna Sartori-Rupp ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Proteins ◽  
Viral Infectivity ◽  
Viral Particles ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Env Protein ◽  
The Impact ◽  
Hiv 1

ABSTRACT The HIV-1 Env protein is exposed at the surface of virions and infected cells. Env fluctuates between different closed and open structural states and these conformations influence both viral infectivity and sensitivity to antibody binding and neutralization. We established a flow virometry assay to visualize Env proteins at the surface of human immunodeficiency virus type 1 (HIV-1) virions. The assay is performed on ultracentrifuged fluorescent viral particles that are stained with a panel of broadly neutralizing antibodies (bNAbs) and nonneutralizing antibodies (nnAbs) that probe different epitopes of Env. We used this assay to compare Env at the surface of producer cells and viral particles and to analyze the effect of Nef, CD4, and SERINC5 on Env accessibility to antibodies. We studied the laboratory-adapted strain NL4-3 and two transmitted/founder viruses, THRO and CH058. We confirm that antibody accessibility varies between viral strains and show that Nef, CD4, and SERINC5 additively impact Env conformations. We further demonstrate that the Env accessibility profile on virions is globally similar to that observed on HIV-1-infected cells, with some noticeable differences. For instance, nnAbs bind to virions more efficiently than to producer cells, likely reflecting changes in Env conformational states on mature viral particles. This test complements other techniques and provides a convenient and simple tool for quantifying and probing the structure of Env at the virion surface and to analyze the impact of viral and cellular proteins on these parameters. IMPORTANCE HIV-1 Env conformation is one of the key parameters determining viral infectivity. The flow virometry-based assay developed in this study allows for the characterization of proteins incorporated in HIV-1 particles. We studied the conformation of HIV-1 Env and the impact that the viral protein Nef and the cellular proteins CD4 and SERINC5 have on Env accessibility to antibodies. Our assay permitted us to highlight some noticeable differences in the conformation of Env between producer cells and viral particles. It contributes to a better understanding of the actual composition of HIV-1 particles.

scholarly journals Differential Biophysical Properties of Infectious Intracellular and Secreted Hepatitis C Virus Particles

2006 ◽  
Vol 80 (22) ◽  
pp. 11074-11081 ◽  
Author(s):  
Pablo Gastaminza ◽  
Sharookh B. Kapadia ◽  
Francis V. Chisari
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Buoyant Density ◽  
Infection Model ◽  
Virus Particles ◽  
Viral Egress ◽  
Viral Particles ◽  
A Cell ◽  
Infected Cells

ABSTRACT The recent development of a cell culture infection model for hepatitis C virus (HCV) permits the production of infectious particles in vitro. In this report, we demonstrate that infectious particles are present both within the infected cells and in the supernatant. Kinetic analysis indicates that intracellular particles constitute precursors of the secreted infectious virus. Ultracentrifugation analyses indicate that intracellular infectious viral particles are similar in size (∼65 to 70 nm) but different in buoyant density (∼1.15 to 1.20 g/ml) from extracellular particles (∼1.03 to 1.16 g/ml). These results indicate that infectious HCV particles are assembled intracellularly and that their biochemical composition is altered during viral egress.

scholarly journals An ultrasensitive planar array p24 Gag ELISA to detect individual HIV-1 viral particles and infected cells

2021 ◽  
Author(s):  
Alberto Bosque ◽  
Callie Levinger ◽  
J Natalie Howard ◽  
Pingtao Tang ◽  
Amit Joshi
Keyword(s):  
Biological Fluids ◽  
Low Frequency ◽  
Viral Reservoirs ◽  
Hiv Persistence ◽  
Viral Particles ◽  
Planar Array ◽  
Infected Cells ◽  
Major Loss ◽  
Hiv 1

Abstract Human Immunodeficiency virus-1 (HIV-1) persistence in the presence of antiretroviral therapy (ART) has halted the development of curative strategies. Measuring HIV persistence is complex due to the low frequency of cells containing virus in vivo. Most of the commercially available assays to date measure nucleic acid. These assays have the advantage of being highly sensitive and allow for the analysis of sequence diversity, intactness of the HIV genome or evaluation of diverse RNA species. However, these assays are limited in evaluating translational competent viral reservoirs. In here, we developed an ultrasensitive p24 ELISA that uses the SimoaTM planar array technology that can detect as low as a single HIV-1 particle and a single HIV-1 infected cell. Furthermore, the assay is optimized to measure very low levels of p24 in different biological fluids without a major loss of sensitivity or reproducibility. Our results demonstrate that the ‘homebrew' planar p24 ELISA immunoassay is a broadly applicable new tool to evaluate HIV persistence in diverse biological fluids.

Comparative study of ultrastructure of HIV and SIV

1990 ◽  
Vol 48 (3) ◽  
pp. 342-343
Author(s):  
Takashi Nakano ◽  
Shunro Imura ◽  
Masuyo Nakai
Keyword(s):  
Osmium Tetroxide ◽  
Staining Method ◽  
Culture Fluid ◽  
Ultrastructural Feature ◽  
Uranyl Acetate ◽  
Negative Staining ◽  
Thin Sections ◽  
Viral Particles ◽  
Infected Cells ◽  
Hiv 1

The ultrastructural feature of AIDS viruses (HIV and SIV) was observed by ultrathin-sectioning and negative staining method, and the surface structures of these viruses were compared.HIV-1 group including, HTLV-III and LAV-1 were used. And in HIV-2 group, LAV-2, which was isolated from a Senegalese AIDS patient, and GH-1, which was isolated from a Ghanan AIDS patient, were used. SIV group was used AGM-1, which was isolated from an African green monkey. The virions were used which was produced from Molt-4 cells after the infection of each viruses of these strains. The infected cells and viral particles, which were collected by centrifugation were fixed with 2% glutaraldehyde (GA), washed with PBS, and postfixed with 1% osmium tetroxide. The specimens were dehydrated in graded ethanol, and embedded in Epon 812. The thin sections were stained with uranyl acetate and lead citrate. On the other hand, for negative staining, 25% GA was added to the supernatant culture fluid and finally concentrated on 2% GA. Then virions were collected by ultracentrifugation.

Gewöhnliche lineare Differentialgleichungen n−ter Ordnung mit Distributionskoeffizienten

1980 ◽  
Vol 85 (3-4) ◽  
pp. 291-298 ◽  
Author(s):  
Rainer Pfaff
Keyword(s):  
Differential Equations ◽  
Continuous Solution ◽  
Initial Conditions ◽  
Linear Differential Equations ◽  
First Order ◽  
Integrable Functions ◽  
Leibniz Formula ◽  
Linear Differential ◽  
Ordinary Linear Differential Equations ◽  
Derivatives Of

SynopsisWe give a formula (4) for a variety of ordinary linear differential equations of order n with distributional coefficients. There appear as coefficients distributions of order k ≦ n/2, i.e. these distributions are kth distributional derivatives of locally L-integrable functions. With a suitable transformation (7) the differential equations can be transformed into first order systems (8) with integrable coefficients. From this follows the existence of a continuous solution, which can be uniquely determined by proper initial conditions.The coefficients in the differential equations considered are chosen as general as possible but such that a transformation into a system with integrable coefficients can be performed, and that all products are defined by Leibniz' formula.

scholarly journals Live-cell observation of cytosolic HIV-1 assembly onset reveals RNA-interacting Gag oligomers

2015 ◽  
Vol 210 (4) ◽  
pp. 629-646 ◽  
Author(s):  
Jelle Hendrix ◽  
Viola Baumgärtel ◽  
Waldemar Schrimpf ◽  
Sergey Ivanchenko ◽  
Michelle A. Digman ◽  
...  
Keyword(s):  
Live Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gag Polyprotein ◽  
Viral Particles ◽  
Infected Cells ◽  
Retroviral Replication ◽  
Gag Assembly ◽  
Reduced Mobility ◽  
Hiv 1

Assembly of the Gag polyprotein into new viral particles in infected cells is a crucial step in the retroviral replication cycle. Currently, little is known about the onset of assembly in the cytosol. In this paper, we analyzed the cytosolic HIV-1 Gag fraction in real time in live cells using advanced fluctuation imaging methods and thereby provide detailed insights into the complex relationship between cytosolic Gag mobility, stoichiometry, and interactions. We show that Gag diffuses as a monomer on the subsecond timescale with severely reduced mobility. Reduction of mobility is associated with basic residues in its nucleocapsid (NC) domain, whereas capsid (CA) and matrix (MA) domains do not contribute significantly. Strikingly, another diffusive Gag species was observed on the seconds timescale that oligomerized in a concentration-dependent manner. Both NC- and CA-mediated interactions strongly assist this process. Our results reveal potential nucleation steps of cytosolic Gag fractions before membrane-assisted Gag assembly.

scholarly journals Accounting for multi-delay effects in an HIV-1 infection model with saturated infection rate, recovery and proliferation of host cells

BIOMATH ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 2012297
Author(s):  
Debadatta Adak ◽  
Nandadulal Bairagi ◽  
Robert Hakl
Keyword(s):  
Infection Rate ◽  
Viral Entry ◽  
Host Cells ◽  
Infection Model ◽  
Multiple Delays ◽  
Delay Effects ◽  
Delayed System ◽  
Infected Cells ◽  
Disease Free ◽  
Hiv 1

Biological models inherently contain delay. Mathematical analysis of a delay-induced model is, however, more difficult compare to its non-delayed counterpart. Difficulties multiply if the model contains multiple delays. In this paper, we analyze a realistic HIV-1 infection model in the presence and absence of multiple delays. We consider self-proliferation of CD4+T cells, nonlinear saturated infection rate and recovery of infected cells due to incomplete reverse transcription in a basic HIV-1 in-host model and incorporate multiple delays to account for successful viral entry and subsequent virus reproduction from the infected cell. Both of delayed and non-delayed system becomes disease-free if the basic reproduction number is less than unity. In the absence of delays, the infected equilibrium is shown to be locally asymptotically stable under some parametric space and unstable otherwise. The system may show unstable oscillatory behaviour in the presence of either delay even when the non-delayed system is stable. The second delay further enhances the instability of the endemic equilibrium which is otherwise stable in the presence of a single delay. Numerical results are shown to be in agreement with the analytical results and reflect quite realistic dynamics observed in HIV-1 infected individuals.

scholarly journals Stabilizing the HIV-1 envelope glycoprotein State 2A conformation

2020 ◽  
Author(s):  
Dani Vézina ◽  
Shang Yu Gong ◽  
William D. Tolbert ◽  
Shilei Ding ◽  
Dung Nguyen ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Coreceptor Binding ◽  
Viral Particles ◽  
A Cell ◽  
Infected Cells ◽  
Cluster A ◽  
State 1 ◽  
Hiv 1 ◽  
Conformation State

The HIV-1 envelope glycoprotein (Env) trimer [(gp120/gp41)3] is a metastable complex expressed at the surface of viral particles and infected cells that samples different conformations. Before engaging CD4, Env adopts an antibody-resistant “closed” conformation (State 1). CD4 binding triggers an intermediate conformation (State 2) and then a more “open” conformation (State 3) that can be recognized by non-neutralizing antibodies (nnAbs) such as those that recognize the coreceptor binding site (CoRBS). Binding of antibodies to the CoRBS permits another family of nnAbs, the anti-cluster A family of Abs which target the gp120 inner domain, to bind and stabilize an asymmetric conformation (State 2A). Cells expressing Env in this conformation are susceptible to antibody-dependent cellular cytotoxicity (ADCC). This conformation can be stabilized by small-molecule CD4 mimetics (CD4mc) or soluble CD4 (sCD4) in combination with anti-CoRBS Ab and anti-cluster A antibodies. The precise stoichiometry of each component that permits this sequential opening of Env remains unknown. Here, we used a cell-based ELISA (CBE) assay to evaluate each component individually. In this assay we used a “trimer mixing” approach by combining wild-type (wt) subunits with subunits impaired for CD4 or CoRBS Ab binding. This enabled us to show that State 2A requires all three gp120 subunits to be bound by sCD4/CD4mc and anti-CoRBS Abs. Two of these subunits can then bind anti-cluster A Abs. Altogether, our data suggests how this antibody vulnerable Env conformation is stabilized. Importance Stabilization of HIV-1 Env State 2A has been shown to sensitize infected cells to ADCC. State 2A can be stabilized by a “cocktail” composed of CD4mc, anti-CoRBS and anti-cluster A Abs. We present evidence that optimal State 2A stabilization requires all three gp120 subunits to be bound by both CD4mc and anti-CoRBS Abs. Our study provides valuable information on how to stabilize this ADCC-vulnerable conformation. Strategies aimed at stabilizing State 2A might have therapeutic utility.

scholarly journals Inside job: how the ESCRTs release HIV-1 from infected cells

2018 ◽  
Vol 46 (5) ◽  
pp. 1029-1036 ◽  
Author(s):  
James H. Hurley ◽  
A. King Cada
Keyword(s):  
Structural Protein ◽  
Endosomal Sorting ◽  
Cellular Processes ◽  
Self Assembling ◽  
Viral Particles ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Membrane Scission ◽  
Endosome Maturation ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) hijacks the host endosomal sorting complex required for transport (ESCRT) proteins in order to release infectious viral particles from the cell. ESCRT recruitment is virtually essential for the production of infectious virus, despite that the main structural protein of HIV-1, Gag, is capable of self-assembling and eventually budding from membranes on its own. Recent data have reinforced the paradigm of ESCRT-dependent particle release while clarifying why this rapid release is so critical. The ESCRTs were originally discovered as integral players in endosome maturation and are now implicated in many important cellular processes beyond viral and endosomal budding. Nearly all of these roles have in common that membrane scission occurs from the inward face of the membrane neck, which we refer to as ‘reverse topology’ scission. A satisfactory mechanistic description of reverse-topology membrane scission by ESCRTs remains a major challenge both in general and in the context of HIV-1 release. New observations concerning the fundamental scission mechanism for ESCRTs in general, and the process of HIV-1 release specifically, have generated new insights in both directions, bringing us closer to a mechanistic understanding.

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