ESTABLISHMENT OF A CELL LINE INFECTED WITH SRS MOUSE LEUKEMIA VIRUS AND ITS BIOLOGICAL CHARACTERISTICS

NIH/3T3 cells were infected with a cell-free extract from the mouse SRS ascltic tumor and propagated at vitro. Experimental results showed that type A and type C virus particles were observed in the cytoplasm of infected NIH/ 3T3 cells by electron-microscopy, X-C assay and reverse transcriptase were both positive. Free proviral-DN A of the leukemia vims was found in the infected NIH/3T3 cell by Southern blot hybridization.Morphologically, the NIH/3T3 cells infected in vitro appeared spherical and formed monolayer cell colonies of various sizes after 24 - 48 hours. When the cultured cells were Inoculated into nude mice (BALB/ c, nu nu ) subcutaneously, flbrosarcoma was Induced, 100%. Inoculation of the cell-free extract of the same cultured cells into Inbred SW-1 newborn mice, resulted in the production of lymphocytic leukemia and lymphoma in 52. 3% within 191 days.

Clinical Trial of Medicinal Synthetic Aluminum-Magnesium Silicate (Antivirt®) on Viral Loads and CD4-Lymphocytes Counts of HIV/AIDS Patients

For clinical trial of Medicinal synthetic Aluminum-magnesium silicate (MSAMS, Antivirt®), on viral loads and CD4-lymphocytes counts of HIV/AIDS patients, 10 volunteers were treated. Their blood samples were tested for viral loads and for CD4-lymphocytes counts, before the treatment and every 4 weeks during the medication. The regimen was: MSAMS (50 mg/kg), MSAMS-stabilized Ampicillin trihydrate (7.5 mg/kg) and immunace extra protection® (1 tablet/day), for 4 weeks. Then, it was reduced to 50 mg/kg (MSAMS) and the immune stimulant. When their viral loads become undetectable, they would be treated for additional 4 weeks. Initially, the Antivirt®-regimen appeared to worsen both HIV infection-load and immune deficiency but later relieved them. Patients’ mean-viral load increased (P = 0.020), from 1820.30 ± 868.75 to 2855.90 ± 960.98, after 4 weeks before reducing (P = 0.030) to 1565.20 ± 743.17, after 8 weeks. Similarly, their mean-CD4-lymphocytes count reduced (P = 0.008) from 496.80 ± 194.39 to 263.90 ± 149.26, after 4 weeks before improving (P = 0.001) to 507.90 ± 133.19, after 8 weeks.

Stability and Hopf bifurcation of a delayed virus infection model with latently infected cells and Beddington-DeAngelis incidence

In this paper,the dynamical behaviors for a five-dimensional virus infection model with Latently Infected Cells and Beddington-DeAngelis incidence are investigated.In the model,four delays which denote the latently infected delay,the intracel-lular delay,virus production period and CTL response delay are considered.We define the basic reproductive number and the CTL immune reproductive number.By using Lyapunov functionals,LaSalle's invariance principle and linearization method,the threshold conditions on the stability of each equilibrium are established.It is proved that when the basic reproductive number is less than or equal to unity,the infection-free equilibrium is globally asy mptot ically stable;when the CTL immune repro-ductive number is less than or equal to unity and the basic reproductive number is greater than unity,the immune free infection equilibrium is globally asymptotically stable;when the CTL immune reproductive number is greater than unity and immune response delay is equal to zero,the immune infection equilibrium is globally asymptotically stable.The results show that immune response delay may destabilize the steady state of infection and lead to Hopf bifurcation.The existence of the Hopf bifurcation is discussed by using immune response delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.

Impact of adaptive immune response and cellular infection on delayed virus dynamics with multi-stages of infected cells

In this investigation,we propose and analyze a virus dynamics model with multi-stages of infected cells.The model incorporates the effect of both humoral and cell-mediated immune responses.We consider two modes of transmissions,virus-to-cell and cell-to-cell.Multiple intracellular discrete-time delays have been integrated into the model.The incidence rate of infection as well as the generation and removal rates of all compartments are described by general nonlinear functions.Wc derive five threshold parameters which determine the existence of the equilibria of the model under consideration.A set of conditions on the general functions has been established which is sufficient to investigate the global stability of the five equilibria of the model.The global asymptotic stability of all equilibria is proven by utilizing Lyapunov function and LaSalle’s invariance principle.The theoretical results are illustrated by numerical simulations of the model with specific forms of the general functions.

Modeling of micropipette aspiration and optical tweezers stretching of erythrocytes with or without Malaria parasite

The erythrocytes play an important role in the human body. The healthy erythrocytes can undergo extremely large deformation while passing through small capillaries. Their infection by Malaria Plasmodium falcipurum （P.f.） will lead to capillary blockage and blood flow obstruction. Many experimental and computational methods have been applied to study the increase in stickiness and decrease in deformability of the Malaria （P.f.） infected erythrocytes. The novelty of this paper lies in the establishment of an multi-component model for investigating mechanical properties of Malaria （P.f.） infected erythrocytes, especially of their enclosed parasites. Finite element method was applied to simulate the erythrocytes＇ deformation in micropipette aspiration and optical tweezers stretching using the computational software ABAQUS. The comparisons between simulations and experiments were able to quantitatively conclude the effects of stiffness and stickiness of the parasitophorous vacuole membrane on the cells＇ deformation, which could not be obtained from experiments directly.

Mathematical Study of the Dynamics of the Development of HIV

Over the history of humankind, they is no disease that has received so much attention as the HIV infection and mathematical models have been applied successfully to the investigation of HIV dynamics. It is, however, of note that, few of these investigations are able to explain the observation that host cell counts reduce while viral load increases as the infection progress. Also, various clinical studies of HIV infection have suggested that high T-cell activation levels are positively correlated with rapid disease development in untreated patients. This activation might be a major reason for the depletion of cells observed in most cases of long-term untreated HIV infection. In this paper, we use a simple mathematical model without treatment to investigate the stability of the system and compare the results with that obtained numerically by the use of MATHCAD. Our model which is a system of differential equations describing the interaction of the HIV and the immune system is divided into three compartments: uninfected CD4T cells, infected CD4Tcells and the virus population. This third compartment includes an extra source of the virus since it is believed that the virus in the blood constitute less than 2% of the total population. We obtain a linearization of the original system, and using Routh-Hurwitz condition for the non-linear system, the critical points are unstable.

Immune evasion by Plasmodium falciparum parasites: converting a host protection mechanism for the parasite′s benefit

Immune evasion is a strategy used by pathogenic microbes to evade the host immune system in order to ensure successful propagation. Immune evasion is particularly important for the blood stages of Plasmodium falciparum, the causative agent of the deadly disease malaria tropica. Because Plasmodium blood stage parasites require human erythrocytes for replication, their ability to evade attack by the human immune system is essential for parasite survival. In order to escape immunity-induced killing, the intraerythrocytic parasites have evolved a variety of evasion mechanisms, including expansion of plasmodial surface proteins, organ-specific sequestration of the infected red blood cells and acquisition of immune-regulatory proteins by the parasite. This review aims to highlight recent advances in the molecular understanding of the immune evasion strategies by P. falciparum, including antigenic variation, surface protein polymorphisms and invasion ligand diversification. The review will further discuss new findings on the regulatory mechanisms applied by P. falciparum to avoid lysis by the human complement as well as killing by immune factors of the mosquito vector.

Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs:a promising therapeutic strategy for HIV cure

Many seminal advances have been made in human immunodeficiency virus(HIV)/AIDS research over the past four decades.Treatment strategies,such as gene therapy and immunotherapy,are yielding promising results to effectively control HIV infection.Despite this,a cure for HIV/AIDS is not envisioned in the near future.A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS,referred to as“selective elimination of host cells capable of producing HIV”(SECH).Similar to the“shock and kill strategy,”the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs.Herein,we comprehensively review the specific mechanisms targeted by the SECH strategy.Briefly,the suggested cocktail of drugs should contain(i)latency reversal agents to promote the latency reversal process in replication-competent reservoir cells,(ii)pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways,and finally(iii)drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells,and by HIV integrase inhibitor drugs.Finally,we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

Efficient control of chronic viral infection by CXCR5-expressing CD8 T cells

Supported by the National Natural Science Foundation of China,the research group led by Prof.Ye Lilin(叶丽林)and Prof.Wu Yuzhang at the Third Military Medical University,Prof.Qi Hai at Tsinghua University and Prof.Xu Jianqing at Fudan University recently reported a novel subset of effect or CD8 T cells.They demonstrated that this subset of cells plays a critical role in viral control during chronic infec-

An exponential for the solutions model of collocation method of the HIV infection CD4＋T cells

In this paper, an exponential method is presented for the approximate solutions of the HIV infection model of CD4＋T. The method is based on exponential polynomi- als and collocation points. This model problem corresponds to a system of nonlinear ordinary differential equations. Matrix relations are constructed for the exponential functions. By aid of these matrix relations and the collocation points, the proposed technique transforms the model problem into a system of nonlinear algebraic equations. By solving the system of the algebraic equations, the unknown coefficients are com- puted and thus the approximate solutions are obtained. The applications of the method for the considered problem are given and the comparisons are made with the other methods.

Mathematical analysis of Hepatitis C Virus infection model in the framework of non-local and non-singular kernel fractionalderivative

In this paper,we study a mathematical model of Hepatitis C Virus(HCV)infection.We present a compartmental mathematical model involving healthy hepatocytes,infected hepatocytes,non-activated dendritic cells,activated dendritic cells and cytotoxic T lymphocytes.The derivative used is of non-local fractional order and with non-singular kernel.The existence and uniqueness of the system is proven and its stability is analyzed.Then,by applying the Laplace Adomian decomposition method for the fractional derivative,we present the semi-analytical solution of the model.Finally,some numerical simulations are performed for concrete values of the parameters and several graphs are plotted to reveal the qualitative properties of the solutions.

Infections caused by Flavimonas oryzihabitans

Objective To assess retrospectively the clinical characteristics and cell immune function of infections caused by Flavimonas oryzihabitans (F oryzihabitans) Methods We indentified 11 cases of F oryzihabitans positive cultures from all microbial cultures collected in our hospital from November 1994 to December 1998 Relevant clinical information was collected, including demographic data, underlying disease, and clinical manifestations of the F. oryzihabitans infections Minimal inhibitory concentrations (MICs) of 15 antimicrobial agents against the 11 F oryzihabitans isolates were determined Cell immune function tests were determined by flow cytometry including T lymphocyte subsets (CD3, CD4, CD8 and ratio CD4/CD8) and NK cells (CD16+56) from peripheral blood Results Six of these patients with infections caused by F oryzihabitans were male, 5 were female and the mean age was 47 64 years (range, 5 to 69 years) All but 1 patients had severe underlying diseases 9 (81 8%) of these patients developed infection while hospitalization and 2 (18 2%) before hospitalization (Cases 2 and 5) 8 (72 7%) of these patients manifested primary F oryzihabitans bacteremia and one each (9 1%) had pleurisy, soft tissue infection and peritonitis All these isolates were susceptible to amikacin, gentamicin and ciprofloxacin, but resistance to cefazolin, nitrofurantoin, penicillin and piperacillin CD3, CD4, CD4/CD8 and CD16+56 value (±s) of these patients were significatly lower than normal values ( P <0 01) The mean time of body temperature fell ≤37℃ after antibiotic treatment in these patients was 3 5 days (range, 1 to 6 days) All clinical symptom caused F oryzihabitans after antibiotic treatment disappeared and all patients recovered Conclusions Infections caused by F oryzihabitans was very few clinically, and relative to underlying diseases and the presence of foreign material Immune function abnormality was among mostly factor for the F oryzihabitans infections

Discrete biological modeling for the immune response to dengue virus

Dengue infection affects more than half of the world’s population,with 1 billion symp-tomatic cases identified per year and several distinct genetic serotypes:DENV 1–4.Transmitted via the mosquito bite,the dengue virus infects Langerhans cells.Monocytes,B lymphocytes,and mast cells infected with dengue virus produce various cytokines although it is not clear which ones are predominant during DHF disease.A mathemat-ical model of the Dengue virus infection is developed according to complex dynamics determined by many factors.Starting from a state of equilibrium that we could define as“virus-free”asymptotically stable with a viral reproduction number lower than one which means a very effective action of the innate immune system:it stops the infectious process,the mathematical analysis of stability in the presence of the virus demonstrates that the proposed model is dynamically influenced.Dengue fever affects more than half of the world’s population,with 1 billion symptomatic cases and multiple genetic serotypes confirmed each year,which simulates a network of interactions between the various populations involved without considering the speeds of the processes in question which are indicated in a separate computation.In this research,a hybrid approach of petri nets is utilized to connect the discrete models of dengue.

Shifted Boubaker Lagrangian approach for solving biological systems

Mathematical models and computer simulations are useful experimental tools for building and testing theories. Many mathematical models in biology can be formulated by a nonlinear system of ordinary differential equations. This work deals with the numerical solution of the hantavirus infection model, the human immunodeficiency virus （HIV） infection model of CD4^＋T cells and the susceptible-infected-removed （SIR） epidemic model using a new reliable algorithm based on shifted Boubaker Lagrangian （SBL） method. This method reduces the solution of such system to a system of linear or non- linear algebraic equations which are solved using the Newton iteration method. The obtained results of the proposed method show highly accurate and valid for an arbitrary finite interval. Also, those are compared with fourth-order Runge-Kutta （RK4） method and with the solutions obtained by some other methods in the literature.