Human Immunodeficiency Virus Particles Research Articles

Novel DNA Biosensing Platform for Detecting HIV Integrase for Highly Sensitive and Quantitative HIV Detection, Diagnosis, and Therapeutic Monitoring.

Straightforward, sensitive, and specific human immunodeficiency virus (HIV) assays are urgently needed. The creation of a point-of-care (POC) device for decentralized diagnostics has the potential to significantly reduce the time to treatment, especially for infectious diseases. Notably, however, many POC solutions proposed to date fall short of meeting the ASSURED guidelines, which are crucial for effective deployment in the field. Herein, we developed a DNA biosensor platform for the specific and quantitative detection of HIV. The platform contains a rolling circle amplification (RCA)-based DNA biosensor and a portable fluorescence detector, in which HIV-encoded integrase (IN) enzyme activity is used as a biomarker to achieve HIV-specific detection. The cleavage and integration reaction of IN on the sensor surface and RCA are combined in this detection platform to perform detection signal cascade amplification, ultimately achieving a detection limit of 0.125 CFU/μL of HIV particles. Moreover, the DNA sensor system exhibited high sensitivity and accuracy for detecting HIV in clinical samples, suggesting that it has potential for application in clinical settings to detect retroviruses other than HIV. In addition, quantitative detection based on this biosensing platform was significantly correlated with the CD4+ lymphocytes count, which can provide guidance for antiretroviral therapy and which affects long-term death risk assessment in HIV patients. Therefore, this DNA biosensing platform based on IN activity is expected to be useful for rapid HIV testing, diagnosis, and treatment monitoring, enabling the development of new POC diagnostic tests and will thus be highly valuable for developing HIV prevention strategies and effective treatments.

HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes

Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD41–4. Although high-resolution structures of Env in a complex with the soluble domains of CD4 have been determined, the binding process is less understood in native membranes5–13. Here we used cryo-electron tomography to monitor Env–CD4 interactions at the membrane–membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env–CD4 complexes organized into clusters and rings, bringing the opposing membranes closer together. Env–CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound to one, two and finally three CD4 molecules, after which Env adopted an open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which probably has consequences for antibody-mediated immune responses and vaccine immunogen design.

A Computational Approach to a Model for HIV and the Immune System Interaction

This study deals with the numerical solution of the human immunodeficiency virus (HIV) infection model, which is a significant problem for global public health. Acquired immunodeficiency syndrome (AIDS) is a communicable disease, and HIV is the causative agent for AIDS, which damages the ability of the body to fight against disease and easily usual innocuous infections attack the body. On entering the body, HIV infects a large amount of CD4+ T-cells and disturbs the supply rate of these cells from the thymus. Herein, we consider the model with variable source terms in which the production of these cells is a monotonically decreasing function of viral load. Based on the reproduction number, we describe the stability of free equilibrium. The continuous Galerkin–Petrov method, in particular the cGP(2)-method, is implemented to determine the numerical solutions of the model. The influence of different parameters on the population dynamics of healthy/infected CD4+ T-cells and free HIV particles are examined, and the results are presented graphically. On the other hand, the model is solved using the fourth-order Runge–Kutta method, and briefly, the RK4-method, and the results of the proposed schemes are compared with those obtained from other classical schemes such as the Bessel collocation method (BCM), Laplace Adomian decomposition method (LADM), perturbation iteration algorithm (PIA), modified variational iteration method (MVIM), differential transform method (DTM), and exponential Galerkin method (EGM), numerically. Furthermore, absolute errors relative to the RK4 method are computed to describe the accuracy of the proposed scheme. It is presented that the cGP(2)-method gains accurate results at larger time step sizes in comparison with the results of the aforementioned methods. The numerical and graphical comparison reveals that the proposed scheme yields more accurate results relative to other traditional schemes from the literature.

Stability analysis of within-host SARS-CoV-2/HIV coinfection model.

The world has been suffering from the coronavirus disease 2019 (COVID‐19) since late 2019. COVID‐19 is caused by a virus called the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The human immunodeficiency virus (HIV) coinfection with SARS‐CoV‐2 has been reported in many patients around the world. This has raised the alarm for the importance of understanding the dynamics of coinfection and its impact on the lives of patients. As in other pandemics, mathematical modeling is one of the important tools that can help medical and experimental studies of COVID‐19. In this paper, we develop a within‐host SARS‐CoV‐2/HIV coinfection model. The model consists of six ordinary differential equations. It depicts the interactions between uninfected epithelial cells, infected epithelial cells, free SARS‐CoV‐2 particles, uninfected CD4+ T cells, infected CD4+ T cells, and free HIV particles. We confirm that the solutions of the developed model are biologically acceptable by proving their nonnegativity and boundedness. We compute all possible steady states and derive their positivity conditions. We choose suitable Lyapunov functions to prove the global asymptotic stability of all steady states. We run some numerical simulations to enhance the global stability results. Based on our model, weak CD4+ T cell immune response or low CD4+ T cell counts in SARS‐CoV‐2/HIV coinfected patient increase the concentrations of infected epithelial cells and SARS‐CoV‐2 viral load. This causes the coinfected patient to suffer from severe SARS‐CoV‐2 infection. This result agrees with many studies which showed that HIV patients are at greater risk of suffering from severe COVID‐19 when infected. More studies are needed to understand the nature of SARS‐CoV‐2/HIV coinfection and the role of different immune responses during infection.

A proposed new paradigm for an anti-AIDS tolerogenic vaccine

Until now, despite 30 years of intensive work, the RV144 human immunodeficiency virus (HIV) vaccine trial initiated in 2003 remains so far the most protective vaccine prototype of all those tested (32% reduction in the infection rate three years after the vaccination) and the HIV epidemic is still spreading worldwide. In addition, antiretroviral therapy (ART) for people living with HIV is given for life as no other pharmacological intervention has allowed to maintain an undetectable viral load after ART withdrawal. Pr Andrieu and colleagues discovered tolerogenic CD8+T-cells that suppress simian immunodeficiency virus (SIV) specific activation, ensuing SIV reverse transcription suppression and viral replication-defective in Chinese macaques vaccinated by intragastric route with inactivated SIV particles + Lactobacillus rhamnosus. Moreover, in HIV-infected elite controllers with specific genetic features (HLA-1-Bw4-80i and KIR3DL1 genes), Pr Andrieu found out that similar tolerogenic CD8+T-cells suppress in the same manner HIV-specific activation, HIV reverse transcription, and HIV replication. These data justify the development of a tolerogenic vaccine composed of inactivated HIV particles + Lactobacillus rhamnosus that could be used as a preventive or therapeutic vaccine.

Negative Staining Transmission Electron Microscopy of HIV Viral Particles Permeabilized with PFO and Capsid Stabilized with IP6.

The human immunodeficiency virus 1 (HIV-1) consists of a viral membrane surrounding the conical capsid. The capsid is a protein container assembled from approximately 1,500 copies of the viral capsid protein (CA), functioning as a reaction and transport chamber for the viral genome after cell entry. Transmission electron microscopy (TEM) is a widely used technique for characterizing the ultrastructure of isolated viral capsids after removal of the viral membrane, which otherwise hinders negative staining of structures inside the viral particle for TEM. Here, we provide a protocol to permeabilize the membrane of HIV-1 particles using a pore-forming toxin for negative staining of capsids, which are stabilized with inositol hexakisphosphate to prevent premature capsid disassembly. This approach revealed the pleomorphic nature of capsids with a partially intact membrane surrounding them. The permeabilization strategy using pore-forming toxins can be readily applied to visualize the internal architecture of other enveloped viruses using TEM. Graphical abstract.

Global stability of HIV/HTLV co-infection model with CTL-mediated immunity

<p style='text-indent:20px;'>Mathematical modeling of human immunodeficiency virus (HIV) and human T-lymphotropic virus type Ⅰ (HTLV-I) mono-infections has received considerable attention during the last decades. These two viruses share the same way of transmission between individuals; through direct contact with certain contaminated body fluids. Therefore, a person can be co-infected with both viruses. In the present paper, we construct and analyze a new HIV/HTLV-I co-infection model under the effect of Cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible CD<inline-formula><tex-math id="M1">\begin{document}$ 4^{+} $\end{document}</tex-math></inline-formula>T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing (active) HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. The HIV can spread by two routes of transmission, virus-to-cell (VTC) and cell-to-cell (CTC). Both active and silent HIV-infected cells can infect the susceptible CD<inline-formula><tex-math id="M2">\begin{document}$ 4^{+} $\end{document}</tex-math></inline-formula>T cells by CTC mechanism. On the other side, HTLV-I has only one mode of transmission via direct cell-to-cell contact. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We calculate all possible equilibria and define the key threshold parameters which govern the existence and stability of all equilibria of the model. We explore the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle's invariance principle. We have discussed the influence of CTL immune response on the co-infection dynamics. We have presented numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we evaluate the effect of HTLV-I infection on the HIV dynamics and vice versa.</p>

Dynamical behaviour of HIV Infection with the influence of variable source term through Galerkin method

In this paper, we formulate the intricate process of Human Immunodeficiency Virus (HIV) infection in a mathematical model. In the formulation of the model, the density of CD4+ T-cells is categorized into healthy and infected classes while the density of free HIV viruses in the human host’s blood is considered a separate class. It is reported that when HIV enters a human’s body, it infects a large amount of CD4+ T-cells and unbalance the supply of new cells from the thymus. Therefore, we incorporate variable source term relying on the viral load for the supply of new cells instead of using a fixed value for the supply of these cells. We implement a continuous Galerkin Petrov time discretization scheme, particularly cGP(2)-scheme to visualize the dynamical behavior of the mentioned model and a detailed description of the effects of different physical parameters of interest are depicts graphically and discuss that how the level of healthy, infected CD4+ T-cells and free HIV particles varies concerning the emerging parameters in the model. In the proposed cGP(2)-method, two unknowns terms can be found by solving a 2×2 block system. This method is accurate of order 3 in the whole time interval and shows even superconvergence of order 4 in the discrete-time points. Furthermore, determine the solution of the model utilizing the fourth-order Runge-Kutta (RK4)-method and find out the absolute errors between the solutions obtained from both approaches. Finally, the validity and reliability of the proposed scheme are verified by comparing the numerical and graphical results with the RK-4 method. We examine the accuracy of the cGP(2)-sheme and observe that it produces more accurate results at relatively larger step sizes as in comparison to RK-4 scheme. Correspondence between the findings of cGP(2)-method and RK4-method reveal that the new technique is a promising tool for obtaining approximate solutions to the nonlinear systems of real-world problems.

Modeling and analysis of a within-host HIV/HTLV-I co-infection.

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that attack the {text {CD4}}^{+}T cells and impair their functions. Both HIV and HTLV-I can be transmitted between individuals through direct contact with certain body fluids from infected individuals. Therefore, a person can be co-infected with both viruses. HIV causes acquired immunodeficiency syndrome (AIDS), while HTLV-I is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Several mathematical models have been developed in the literature to describe the within-host dynamics of HIV and HTLV-I mono-infections. However, modeling a within-host dynamics of HIV/HTLV-I co-infection has not been involved. The present paper is concerned with the formulation and investigation of a new HIV/HTLV-I co-infection model under the effect of Cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible {text {CD4}}^{+}T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. The HIV can spread by virus-to-cell transmission. On the other side, HTLV-I has two modes of transmission, (i) horizontal transmission via direct cell-to-cell contact through the virological synapse, and (ii) vertical transmission through the mitotic division of Tax-expressing HTLV-infected cells. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We define a set of threshold parameters which govern the existence and stability of all equilibria of the model. We explore the global asymptotic stability of all equilibria by utilizing Lyapunov function and Lyapunov–LaSalle asymptotic stability theorem. We have presented numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we evaluate the effect of HTLV-I infection on the HIV dynamics and vice versa.

Structural Domains of the Herpes Simplex Type 1 gD Protein that Restrict HIV-1 Particle Infectivity.

Previously, we showed that the presence of the herpes simplex virus type 1 (HSV-1) gD glycoprotein but not gB potently restricted HIV-1 particle infectivity. This restriction was characterized by incorporation of HSV-1 gD and the exclusion of the HIV-1 gp120/gp41 from budding virus particles. To determine the structural domains involved in gD restriction of HIV-1, a series of deletion mutants and chimeric proteins between gD and the non-restrictive gB were generated. Our results show that deletion of the cytoplasmic tail domain (CTD) of gD or that replacement of the transmembrane domain (TMD) with the TMD from gB slightly reduced restriction activity. However, replacement of the gD CTD with that of gB resulted in lower cell surface expression, significantly less incorporation into HIV-1 particles, and inefficient restriction of the release of infectious HIV-1. Analysis of gB/gD chimeric proteins revealed that removal of the gB CTD or replacement with gD CTD resulted in enhanced surface expression and an increase in restriction activity. Finally, we show that expression of gD without other HSV-1 proteins resulted in gD fractionation into detergent resistant membranes (DRM) and that gD co-localized with the raft marker GM1, which may partially explain its incorporation into budding virus particles. Taken together, our results suggest that expression of gD at the cell surface is likely a major factor but that other intrinsic properties are also involved in the gD-mediated restriction of HIV-1 particle infectivity.IMPORTANCE Previously, we showed that unlike the HSV-1, the presence of the gD glycoprotein in virus producer cells but not gB potently restricted HIV-1 particle infectivity. To better understand the relationship between cell surface expression, virus incorporation and restriction of HIV-1, we analyzed a series of deletion mutants and chimeric proteins in which domains of gD and gB were swapped. Our results indicate that: a) gD/gB chimeras having the cytoplasmic domain (CTD) of gB significantly reduced cell surface expression, release from cells, incorporation into virus, and reduced HIV-1 restriction; b) removal of the gB CTD or replacement with the gD CTD resulted in better surface expression, incorporation into HIV-1, and enhanced restriction; and c) the transmembrane domain of gB can influence transport and ultimately effect incorporation of gB into HIV-1. Overall, these data support a role for gD surface expression as crucial to restriction of infectious HIV-1 release.

Modeling and stability analysis of HIV/HTLV-I co-infection

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that infect the susceptible CD[Formula: see text]T cells. It is known that HIV and HTLV-I have in common a way of transmission through direct contact with certain body fluids related to infected individuals. Therefore, it is not surprising that a mono-infected person with one of these viruses can be co-infected with the other virus. In the literature, a great number of mathematical models has been presented to describe the within-host dynamics of HIV or HTLV-I mono-infection. However, the within-host dynamics of HIV/HTLV-I co-infection has not been modeled. In this paper, we develop a new within-host HIV/HTLV-I co-infection model. The model includes the impact of Cytotoxic T lymphocytes (CTLs) immune response, which is important to control the progression of viral co-infection. The model describes the interaction between susceptible CD[Formula: see text]T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. We first show the nonnegativity and boundedness of the model’s solutions and then we calculate all possible equilibria. We derive the threshold parameters which govern the existence and stability of all equilibria of the model. We prove the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle’s invariance principle. We have presented numerical simulations to illustrate the effectiveness of our main results. In addition, we discuss the effect of HTLV-I infection on the HIV-infected patients and vice versa.

The Usefulness of HIV-1p24 in Detecting the Presence of HIV Infection in Histopathology Tissue Specimens

Introduction HIV (human immunodeficiency virus)-associated immunodeficiency is the single most important acquired immunodeficiency in humans, underlying several diseases. The presence of HIV infection may be unsuspected or undetected in tissues due to latency or failure of the consulting physician to document it on the requisition form. HIV-1p24 protein is a component of the HIV particle capsid that can be exploited serologically and immunohistochemically to detect the presence of HIV infection. This study aimed to assess the usefulness of HIV-1 p24 immunohistochemistry in detecting the presence of HIV infection in histopathology tissues in a resource-challenged setting. Materials and Methods HIV-1p24 immunohistochemical expression was evaluated in 59 cases from the archives of both Nnamdi Azikiwe University Teaching Hospital (NAUTH) and Pathocon Specialist Clinic and Research Institute over a 10-year period. Pathology consult forms of all clinically and morphologically suspected cases of Kaposi sarcoma and their blocks were retrieved, recut, and reviewed using hematoxylin and eosin, and then subjected to HIV-1p24 immunohistochemical staining. Results Of the 59 cases, 38 expressed p24, whereas 21 were negative. Fifteen of the positive cases had no prior documented evidence of HIV infection. Five cases with clinically known statuses, four positive and one negative, were found to be negative and positive, respectively, following HIV-1p24 immunohistochemical staining, probably due to usage of ELISA (enzyme-linked immunosorbent assay) detection kit only and long term antiretroviral therapy. HIV infection was commoner in the third and fourth decades of life. Conclusion HIV-1p24 is a useful low-cost immunohistochemical marker in detecting the presence of HIV infection in histopathology specimens, even in previously unsuspected cases.

HTLV/HIV Dual Infection: Modeling and Analysis

Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) are two famous retroviruses that share similarities in their genomic organization, and differ in their life cycle as well. It is known that HTLV-I and HIV have in common a way of transmission via direct contact with certain body fluids related to infected patients. Thus, it is not surprising that a single-infected person with one of these viruses can be dually infected with the other virus. In the literature, many researchers have devoted significant efforts for modeling and analysis of HTLV or HIV single infection. However, the dynamics of HTLV/HIV dual infection has not been formulated. In the present paper, we formulate an HTLV/HIV dual infection model. The model includes the impact of the Cytotoxic T lymphocyte (CTLs) immune response, which is important to control the dual infection. The model describes the interaction between uninfected CD4+T cells, HIV-infected cells, HTLV-infected cells, free HIV particles, HIV-specific CTLs, and HTLV-specific CTLs. We establish that the solutions of the model are non-negative and bounded. We calculate all steady states of the model and deduce the threshold parameters which determine the existence and stability of the steady states. We prove the global asymptotic stability of all steady states by utilizing the Lyapunov function and Lyapunov–LaSalle asymptotic stability theorem. We solve the system numerically to illustrate the our main results. In addition, we compared between the dynamics of single and dual infections.

Analysis of a within-host HIV/HTLV-I co-infection model with immunity

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that attack the immune cells and impair their functions. Both HIV and HTLV-I can be transmitted between individuals through direct contact with certain body fluids from infected individuals. Therefore, a person can be co-infected with both viruses. HIV causes acquired immunodeficiency syndrome, while HTLV-I is the causative agent for adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Several mathematical models have been developed in the literature to describe the within-host dynamics of HIV and HTLV-I mono-infections. However, modeling a within-host dynamics of HIV/HTLV-I co-infection has not been involved. In the present paper, we are concerned to formulate and analyze a new HIV/HTLV co-infection model under the effect of Cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible CD4+T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. The HIV can spread by two routes of transmission, virus-to-cell and cell-to-cell. On the other side, HTLV-I has two modes of transmission, (i) horizontal transmission via direct cell-to-cell contact, and (ii) vertical transmission through mitotic division of Tax-expressing HTLV-infected cells. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We define a set of threshold parameters which govern the existence and stability of all equilibria of the model. We explore the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle's invariance principle. We have presented numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we evaluate the effect of HTLV-I infection on the HIV dynamics and vice versa.

Convergent Evolution of HLA-C Downmodulation in HIV-1 and HIV-2.

HLA-C-mediated antigen presentation induces the killing of human immunodeficiency virus (HIV)-infected CD4+ T cells by cytotoxic T lymphocytes (CTLs). To evade killing, many HIV-1 group M strains decrease HLA-C surface levels using their accessory protein Vpu. However, some HIV-1 group M isolates lack this activity, possibly to prevent the activation of natural killer (NK) cells. Analyzing diverse primate lentiviruses, we found that Vpu-mediated HLA-C downregulation is not limited to pandemic group M but is also found in HIV-1 groups O and P as well as several simian immunodeficiency viruses (SIVs). We show that Vpu targets HLA-C primarily at the protein level, independently of its ability to suppress NF-κB-driven gene expression, and that in some viral lineages, HLA-C downregulation may come at the cost of efficient counteraction of the restriction factor tetherin. Remarkably, HIV-2, which does not carry a vpu gene, uses its accessory protein Vif to decrease HLA-C surface expression. This Vif activity requires intact binding sites for the Cullin5/Elongin ubiquitin ligase complex but is separable from its ability to counteract APOBEC3G. Similar to HIV-1 Vpu, the degree of HIV-2 Vif-mediated HLA-C downregulation varies considerably among different virus isolates. In agreement with opposing selection pressures in vivo, we show that the reduction of HLA-C surface levels by HIV-2 Vif is accompanied by increased NK cell-mediated killing. In summary, our results highlight the complex role of HLA-C in lentiviral infections and demonstrate that HIV-1 and HIV-2 have evolved at least two independent mechanisms to decrease HLA-C levels on infected cells.IMPORTANCE Genome-wide association studies suggest that HLA-C expression is a major determinant of viral load set points and CD4+ T cell counts in HIV-infected individuals. On the one hand, efficient HLA-C expression enables the killing of infected cells by cytotoxic T lymphocytes (CTLs). On the other hand, HLA-C sends inhibitory signals to natural killer (NK) cells and enhances the infectivity of newly produced HIV particles. HIV-1 group M viruses modulate HLA-C expression using the accessory protein Vpu, possibly to balance CTL- and NK cell-mediated immune responses. Here, we show that the second human immunodeficiency virus, HIV-2, can use its accessory protein Vif to evade HLA-C-mediated restriction. Furthermore, our mutational analyses provide insights into the underlying molecular mechanisms. In summary, our results reveal how the two human AIDS viruses modulate HLA-C, a key component of the antiviral immune response.

GLOBAL PROPERTIES OF HIV DYNAMICS MODELS INCLUDING IMPAIRMENT OF B-CELL FUNCTIONS

In this paper, we develop mathematical models that include impairment of B-cell functions in order to study HIV dynamics. Two forms of the incidence rate have been considered, bilinear and general nonlinear. Three types of infected cells have been incorporated into the models, namely latently infected, short-lived productively infected and long-lived productively infected. The models have at most two equilibria, whose existence is characterized by means of the basic reproduction number [Formula: see text]. The global stability of each equilibrium is proven by using the Lyapunov method. The effects of impairment of B-cell functions and of antiviral treatment on the human immunodeficiency virus (HIV) dynamics are studied. We have shown that if the functions of B-cell are impaired, then the concentration of HIV increases in the plasma. Moreover, we have determined the minimal drug efficacy which is required to reduce the concentration of HIV particles to a lower level. We have shown that a more accurate computation of drug efficacy can be performed by using our proposed model. Our theoretical results are illustrated by means of numerical simulations.

Cell Proteins Interacting with the Human Immunodeficiency Virus in Immunoblotting can be Detected by R5- or X4- Tropic Human Immunodeficiency Virus Particles.

Introduction:The present study reported a new immunoblot assay, with revelation by R5- or X4-whole free human immunodeficiency virus (HIV) particles or recombinant gp160.Materials and Methods:The assay was optimized to identify cell proteins interacting with HIV. Whole cell lysates were prepared from peripheral blood lymphocytes (PBLs), dendritic cells (DC), monocyte-derived macrophage (MDM), and Henrietta Lacks (Hela, wild-type or transfected with DC-specific intracellular adhesion molecule-3-Grabbing Non-Integrin, HeLa) and Human endometrial cells (HEC-1A) lines; HIV particles used were the R5-tropic HIV-1JRCSF and the X4-tropic HIV-1NDK.Results:Experiments with PBL lysates and both viruses demonstrated different bands, including a unique band at 105–117 kDa in addition to nonspecific bands. The 105–117 kDa band migrated at the same level of that observed in controls using total PBL lysate and anti-CD4 mAb for detection and thus likely corresponds to the cluster difference (CD) 4 complex. Blots using lysates of DCs, MDM, HeLa cell line, and HEC-1A cell line allowed identifying several bands that positions were similar to that seen by recombinant gp160 or whole R5- or X4-HIV particles.Conclusion:Blot of whole lysates of various HIV target cells is recognized by free HIV particles and allows identifying a wide range of HIV-interacting cell proteins. Such optimized assay could be useful to recognize new cellular HIV attachment proteins.

Global Properties of a Delay-Distributed HIV Dynamics Model Including Impairment of B-Cell Functions

In this paper, we construct an Human immunodeficiency virus (HIV) dynamics model with impairment of B-cell functions and the general incidence rate. We incorporate three types of infected cells, (i) latently-infected cells, which contain the virus, but do not generate HIV particles, (ii) short-lived productively-infected cells, which live for a short time and generate large numbers of HIV particles, and (iii) long-lived productively-infected cells, which live for a long time and generate small numbers of HIV particles. The model considers five distributed time delays to characterize the time between the HIV contact of an uninfected CD4 + T-cell and the creation of mature HIV. The nonnegativity and boundedness of the solutions are proven. The model admits two equilibria, infection-free equilibrium E P 0 and endemic equilibrium E P 1 . We derive the basic reproduction number R 0 , which determines the existence and stability of the two equilibria. The global stability of each equilibrium is proven by utilizing the Lyapunov function and LaSalle’s invariance principle. We prove that if R 0 < 1 , then E P 0 is globally asymptotically stable, and if R 0 > 1 , then E P 1 is globally asymptotically stable. These theoretical results are illustrated by numerical simulations. The effect of impairment of B-cell functions, time delays, and antiviral treatment on the HIV dynamics are studied. We show that if the functions of B-cells are impaired, then the concentration of HIV is increased in the plasma. Moreover, we observe that the time delay has a similar effect to drug efficacy. This gives some impression for developing a new class of treatments to increase the delay period and then suppress the HIV replication.

The role of CD4 T cells in immune system activation and viral reproduction in a simple model for HIV infection

CD4 T cells play a fundamental role in the adaptive immune response including the stimulation of cytotoxic lymphocytes (CTLs). Human immunodeficiency virus (HIV) which infects and kills CD4 T cells causes progressive failure of the immune system. However, HIV particles are also reproduced by the infected CD4 T cells. Therefore, during HIV infection, infected and healthy CD4 T cells act in opposition to each other, reproducing virus particles and activating and stimulating cellular immune responses, respectively. In this investigation, we develop and analyze a simple system of four ordinary differential equations that accounts for these two opposing roles of CD4 T cells. The model illustrates the importance of the CTL immune response during the asymptomatic stage of HIV infection. In addition, the solution behavior exhibits the two stages of infection, asymptomatic and final AIDS stages. In the model, a weak immune response results in a short asymptomatic stage and faster development of AIDS, whereas a strong immune response illustrates the long asymptomatic stage. A model with a latent stage for infected CD4 T cells is also investigated and compared numerically with the original model. The model shows that strong stimulation of CTLs by CD4 T cells is necessary to prevent progression to the AIDS stage.

A lipid-based partitioning mechanism for selective incorporation of proteins into membranes of HIV particles.

Particles that bud off from the cell surface, including viruses and microvesicles, typically have a unique membrane protein composition distinct from that of the originating plasma membrane. This selective protein composition enables viruses to evade the immune response and infect other cells. But how membrane proteins sort into budding viruses such as human immunodeficiency virus (HIV) remains unclear. Proteins could passively distribute into HIV-assembly-site membranes producing compositions resembling pre-existing plasma-membrane domains. Here, we demonstrate that proteins instead sort actively into HIV-assembly-site membranes, generating compositions enriched in cholesterol and sphingolipids that undergo continuous remodelling. Proteins are recruited into and removed from the HIV assembly site through lipid-based partitioning, initiated by oligomerization of the HIV structural protein Gag. Changes in membrane curvature at the assembly site further amplify this sorting process. Thus, a lipid-based sorting mechanism, aided by increasing membrane curvature, generates the unique membrane composition of the HIV surface.