• Title/Summary/Keyword: Virus dynamics

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GLOBAL ANALYSIS FOR A DELAY-DISTRIBUTED VIRAL INFECTION MODEL WITH ANTIBODIES AND GENERAL NONLINEAR INCIDENCE RATE

  • Elaiw, A.M.;Alshamrani, N.H.
    • Journal of the Korean Society for Industrial and Applied Mathematics
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    • v.18 no.4
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    • pp.317-335
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    • 2014
  • In this work, we investigate the global stability analysis of a viral infection model with antibody immune response. The incidence rate is given by a general function of the populations of the uninfected target cells, infected cells and free viruses. The model has been incorporated with two types of intracellular distributed time delays to describe the time required for viral contacting an uninfected cell and releasing new infectious viruses. We have established a set of conditions on the general incidence rate function and determined two threshold parameters $R_0$ (the basic infection reproduction number) and $R_1$ (the antibody immune response activation number) which are sufficient to determine the global dynamics of the model. The global asymptotic stability of the equilibria of the model has been proven by using Lyapunov theory and applying LaSalle's invariance principle.

Age-dependent immune response in pigs against foot-and-mouth disease virus in vitro

  • Roh, Jae-Hee;Bui, Ngoc Anh;Lee, Hu Suk;Bui, Vuong Nghia;Dao, Duy Tung;Vu, Thanh Thi;Hoang, Thuy Thi;So, Kyoung-Min;Yi, Seung-Won;Kim, Eunju;Hur, Tai-Young;Oh, Sang-Ik
    • Journal of Animal Science and Technology
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    • v.63 no.6
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    • pp.1376-1385
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    • 2021
  • Foot-and-mouth disease, one of the most contagious diseases in cloven-hoofed animals, causes significant economic losses. The pathogenesis of foot-and-mouth disease virus (FMDV) infection is known to differ with age of the animals. In this study, we aimed to reveal the difference in immunological response in the initial stage of FMDV infection between piglets and adult pigs. Peripheral blood mononuclear cells (PBMCs) were isolated from 3 piglets (8 weeks old) and 3 pigs (35 weeks old) that were not vaccinated against FMDV. O-type FMDV (2 × 102 median tissue culture infectious dose) was inoculated into porcine PBMCs and the cells were incubated at 37.0℃ under 5% CO2 for various time periods (0, 1, 3, 6, 12, 24, and 48 h). The total RNA was obtained from the FMDV-inoculated PBMCs after each time point, and the virus titer was investigated in these RNA samples. Furthermore, dynamics of mRNA expression of the six tested cytokines (interferon [IFN]-α, IFN-γ, interleukin [IL]-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) in FMDV-inoculated porcine PBMCs were evaluated by time-series analysis to determine the differences, if any, based on the age of the pigs. The PBMCs of piglets contained the highest quantity of FMDV mRNA at 6 hours post-inoculation (hpi), and the PBMCs of pigs had the highest quantity of FMDV mRNA at 3 hpi. The mean cycle threshold-value in the PBMCs steadily decreased after the peak time point in the piglets and pigs (6 and 3 hpi, respectively). The dynamics of mRNA expression of all cytokines except TNF-α showed age-dependent differences in FMDV-inoculated PBMCs. The mRNA expression of most cytokines was more pronounced in the piglets than in the pigs, implying that the immune response against FMDV showed an age-dependent difference in pigs. In conclusion, within 48 hpi, the 8-week-old piglets responded more rapidly and were more sensitive to FMDV infection than the 35-week-old pigs, which could be associated with the difference in the pathogenesis of FMDV infection among the pigs. These results provide valuable insights into the mechanisms underlying the age-dependent differences in immune response in pigs against FMDV infection.

Mathematical Modelling for the Transmission Dynamics of HIV infection and AIDS (HIV감염과 AIDS의 전파특성에 관한 수학적 모델화)

  • Chung, Hyeng-Hwan;Joo, Seok-Min;Chung, Mun-Gyu;Lee, Kwang-Woo
    • The Transactions of the Korean Institute of Electrical Engineers A
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    • v.48 no.2
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    • pp.89-95
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    • 1999
  • This study investigates the population model of the spread of HIV/AIDS which the infection is generated by an infectious individual in a population of susceptible. A mathematical model is presented for the transmission dynamics of HIV infection within the communities of homosexual males. The pattern on the epidemic character of HIV, the causative agent of AIDS, was analysed by the mathematical model of AIDS system which is derived according to the ecological relationship between five epidemilogic states of individuals. The computer simulation was performed using real data and the following conclusions are drawn on the basis of the simulations. 1. The model structure and the algorithm described n the thesis is good. 2. In proportion to increase Ro, the population of AIDS patient increases and the time of its widespread reaches earlier. 3. The AIDS patients will be maximum between 7 and 21 years after an attack of AIDS and widespread between 10 and 20 years. 4. Considering the properties of the incubation periods, the maximum number of infected person is increased, and the attack rate is decreased.

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Computer-aided drug design of Azadirachta indica compounds against nervous necrosis virus by targeting grouper heat shock cognate protein 70 (GHSC70): quantum mechanics calculations and molecular dynamic simulation approaches

  • Islam, Sk Injamamul;Saloa, Saloa;Mahfuj, Sarower;Islam, Md Jakiul;Jahan Mou, Moslema
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.33.1-33.17
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    • 2022
  • Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of -9.7, -9.5, -9.1, and -9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.

Real-Time Temporal Dynamics of Bicistronic Expression Mediated by Internal Ribosome Entry Site and 2A Cleaving Sequence

  • Lee, Soomin;Kim, Jeong-Ah;Kim, Hee-Dae;Chung, Sooyoung;Kim, Kyungjin;Choe, Han Kyoung
    • Molecules and Cells
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    • v.42 no.5
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    • pp.418-425
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    • 2019
  • Multicistronic elements, such as the internal ribosome entry site (IRES) and 2A-like cleavage sequence, serve crucial roles in the eukaryotic ectopic expression of exogenous genes. For utilization of multicistronic elements, the cleavage efficiency and order of elements in multicistronic vectors have been investigated; however, the dynamics of multicistronic element-mediated expression remains unclear. Here, we investigated the dynamics of encephalomyocarditis virus (EMCV) IRES- and porcine teschovirus-1 2A (p2A)-mediated expression. By utilizing real-time fluorescent imaging at a minute-level resolution, we monitored the expression of fluorescent reporters bridged by either EMCV IRES or p2A in two independent cultured cell lines, HEK293 and Neuro2a. We observed significant correlations for the two fluorescent reporters in both multicistronic elements, with a higher correlation coefficient for p2A in HEK293 but similar coefficients for IRES-mediated expression and p2A-mediated expression in Neuro2a. We further analyzed the causal relationship of multicistronic elements by convergent cross mapping (CCM). CCM revealed that in all four conditions examined, the expression of the preceding gene causally affected the dynamics of the subsequent gene. As with the cross correlation, the predictive skill of p2A was higher than that of IRES in HEK293, while the predictive skills of the two multicistronic elements were indistinguishable in Neuro2a. To summarize, we report a significant temporal correlation in both EMCV IRES- and p2A-mediated expression based on the simple bicistronic vector and real-time fluorescent monitoring. The current system also provides a valuable platform to examine the dynamic aspects of expression mediated by diverse multicistronic elements under various physiological conditions.

GLOBAL STABILITY OF HIV INFECTION MODELS WITH INTRACELLULAR DELAYS

  • Elaiw, Ahmed;Hassanien, Ismail;Azoz, Shimaa
    • Journal of the Korean Mathematical Society
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    • v.49 no.4
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    • pp.779-794
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    • 2012
  • In this paper, we study the global stability of two mathematical models for human immunodeficiency virus (HIV) infection with intra-cellular delays. The first model is a 5-dimensional nonlinear delay ODEs that describes the interaction of the HIV with two classes of target cells, $CD4^+$ T cells and macrophages taking into account the saturation infection rate. The second model generalizes the first one by assuming that the infection rate is given by Beddington-DeAngelis functional response. Two time delays are used to describe the time periods between viral entry the two classes of target cells and the production of new virus particles. Lyapunov functionals are constructed and LaSalle-type theorem for delay differential equation is used to establish the global asymptotic stability of the uninfected and infected steady states of the HIV infection models. We have proven that if the basic reproduction number $R_0$ is less than unity, then the uninfected steady state is globally asymptotically stable, and if the infected steady state exists, then it is globally asymptotically stable for all time delays.

Numerical Analysis for Characteristic of Flow and Disinfection Performance with Variation of Guide Wall in Clearwell (도류벽 형태에 따른 정수지 내 유동 특성과 소독능 변화에 대한 수치 해석적 연구)

  • Lee, Suk-Won;Park, Jun-Jung;Rhee, Gwang-Hoon
    • Proceedings of the SAREK Conference
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    • 2006.06a
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    • pp.767-772
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    • 2006
  • The SWTR(Surface Water Treatment Rule) requires achieving removal 99.9% Giardia and 99.99% Virus. To remove Giardia and Virus, disinfection process is essential process. CT is important index for Disinfection performance. CT value is expressed by CXT. C is represented by disinfection concentration and T is represented by $T_{10}$ which means 90% contact time in clearwell. To improve Disinfection performance, it is desirable to increase $T_{10}$. Primary factor affected $T_{10}$ is flow Pattern. Because guide wall change that flow pattern is uniform, we have installed guide wall to increase $T_{10}$. In this paper, we have performed numerical analysis for clearwell installed symmetric guide wall and center divided guide wall using CFD. We have analyzed flow pattern and $T_{10}$ in each clearwell. And. we compare symmetric guide wall with center divided guide wall in flow pattern and $T_{10}$.

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v-Crk Induces Rac-dependent Membrane Ruffling and Cell Migration in CAS-deficient Embryonic Fibroblasts

  • Sung, Bong Hwan;Yeo, Myoung Gu;Oh, Hye Jin;Song, Woo Keun
    • Molecules and Cells
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    • v.25 no.1
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    • pp.131-137
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    • 2008
  • Crk-associated substrate (CAS) is a focal adhesion protein that is involved in integrin signaling and cell migration. CAS deficiency reduces the migration and spreading of cells, both of which are processes mediated by Rac activation. We examined the functions of v-Crk, the oncogene product of the CT10 virus p47gag-crk, which affects cell migration and spreading, membrane ruffling, and Rac activation in CAS-deficient mouse embryonic fibroblasts (CAS-/- MEFs). CAS-/- MEFs showed less spreading than did CAS+/+ MEFs, but spreading was recovered in mutant cells that expressed v-Crk (CAS-/-v-Crk MEF). We observed that the reduction in spreading was linked to the formation of membrane ruffles, which were accompanied by Rac activation. In CAS-/- MEFs, Rac activity was significantly reduced, and Rac was not localized to the membrane. In contrast, Rac was active and localized to the membrane in CAS-/-v-Crk MEFs. Lamellipodia protrusion and ruffle retraction velocities were both reduced in CAS-/- MEFs, but not in CAS-/-v-Crk MEFs. We also found that microinjection of anti-gag antibodies inhibited the migration of CAS-/-v-Crk MEFs. These findings indicate that v-Crk controls cell migration and membrane dynamics by activating Rac in CAS-deficient MEFs.

Characterization of Binding Mode of the Heterobiaryl gp120 Inhibitor in HIV-1 Entry: A Molecular Docking and Dynamics Simulation Study

  • Gadhe, Changdev G.;Kothandan, Gugan;Cho, Seung Joo
    • Bulletin of the Korean Chemical Society
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    • v.34 no.8
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    • pp.2466-2472
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    • 2013
  • Human immunodeficiency virus type-1 (HIV-1) is a causative agent of Acquired immunodeficiency syndrome (AIDS), which has affected a large population of the world. Viral envelope glycoprotein (gp120) is an intrinsic protein for HIV-1 to enter into human host cells. Molecular docking guided molecular dynamics (MD) simulation was performed to explore the interaction mechanism of heterobiaryl derivative with gp120. MD simulation result of inhibitor-gp120 complex demonstrated stability. Our MD simulation results are consistent with most of the previous mutational and modeling studies. Inhibitor has an interaction with the CD4 binding region. Van der Waals interaction between inhibitor and Val255, Thr257, Asn425, Met426 and Trp427 were important. This preliminary MD model could be useful in exploiting heterobiaryl-gp120 interaction in greater detail, and will likely to shed lights for further utilization in the development of more potent inhibitors.

GLOBAL STABILITY OF THE VIRAL DYNAMICS WITH CROWLEY-MARTIN FUNCTIONAL RESPONSE

  • Zhou, Xueyong;Cui, Jingan
    • Bulletin of the Korean Mathematical Society
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    • v.48 no.3
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    • pp.555-574
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    • 2011
  • It is well known that the mathematical models provide very important information for the research of human immunodeciency virus type. However, the infection rate of almost all mathematical models is linear. The linearity shows the simple interaction between the T-cells and the viral particles. In this paper, a differential equation model of HIV infection of $CD4^+$ T-cells with Crowley-Martin function response is studied. We prove that if the basic reproduction number $R_0$ < 1, the HIV infection is cleared from the T-cell population and the disease dies out; if $R_0$ > 1, the HIV infection persists in the host. We find that the chronic disease steady state is globally asymptotically stable if $R_0$ > 1. Numerical simulations are presented to illustrate the results.