Virus Infection Model Research Articles

Fractional perspective evaluation of chikungunya infection with saturated incidence functions

It is significant to investigate the transmission dynamics of vector-borne infection because it has a global impact, can help predict and prevent future outbreaks, is important for understanding the impact of climate change on public health, can lead to more effective control strategies, and can improve our comprehension of the dynamics of these infections. Our paper presents a new model for chikungunya virus infection, which considers treatment and vaccination, using the Atangana-Baleanu derivative within the framework of the Caputo definition. First of all, we examine the positivity and uniqueness of the solution for the model. Then, we find out the fundamental results of the suggested model, such as the steady-state without infection and the R0 value that indicates endemicity pertaining to the system. Furthermore, we verify the local asymptotic stability of the infection-free steady-state. Through the application of fixed-point theory, we demonstrate the existence of the solution and propose a numerical methodology to investigate the dynamic behavior of the model. Finally, we performed simulations to demonstrate the effects of vaccination, transmission probability, treatment, and index of memory on the system's solution pathways. The findings of this research suggest the most sensitive parameters of the system responsible for the control and prevention of the infection. Emphasizing the significance of the memory index as an attractive parameter, we propose its consideration to the policy makers as a control parameter for the prevention of the infection.

Fractional order PD control of the Hopf bifurcation of HBV viral systems with multiple time delays

This paper will explore a fractional-order hepatitis B virus (HBV) infection model that takes into account cell-cell and virus-cell transmission and multiple treatment modalities. The desired control strategy is realized by means of a fractional order PD controller. Firstly, we calculated the basic regeneration number and equilibrium point of the HBV model. Afterwards, for the uncontrolled HBV virus system, the adequate conditions for both stability and Hopf bifurcation are systematically investigated via choosing the appropriate time delay as a parameter for bifurcation. Subsequently, under fractional order PD controller, the effect of a proposed controller on system stability and Hopf bifurcation is studied. The desired dynamic characteristics can be obtained afterwards. Finally, numerical simulations show that all three treatments significantly reduce R0. The onset of oscillations can be delayed by decreasing the order of the fractional order. There are three control pathways for fractional order PD control, and the generation of bifurcation can also be delayed by changing the gain parameter. Using the above methods, the diffusion of HBV virus particles in the body can be effectively controlled. The conclusions drawn in this paper are extremely novel and have potential theoretical value for the future treatment of hepatitis B illness.

A Numerical Application of the Chebyshev Operational Matrix Method for HIV Infection of CD4+T-cells

In this research study, we aim to approximate a solution for the mathematical model of the Human Immunodeficiency Virus (HIV) infection of CD4+T-cells. An operational matrix method based on Chebyshev orthogonal polynomials has been adapted to obtain numerical solutions for the model of HIV infection of CD4+T-cells. The proposed numerical scheme is built on a system of a nonlinear algebraic equation, including coefficients of a finite Chebyshev series that are represented the approximate solutions of the model. Results are compared to existing methods to verify the accuracy of the numerical scheme.

Human skin organoids are valid models of mpox virus infection.

Human skin organoids are valid models of mpox virus infection.

A novel investigation of the hepatitis B virus using a fractional operator with a non-local kernel

In order to understand and manage infectious illnesses, mathematical models are extremely important. They support decision making by researchers and public health workers in predicting the spread of diseases, evaluate the results of interventions, and gathering data. This study considers a fractionalized hepatitis B virus (HBV) infection model with cell cure. The Atangana Baleanu fractional model was initially established for the epidemic issue. This paper analyses the fractional form that makes up the HBV infection model utilizing the numerical methodology, homotopy analysis transform method (HATM). The suggested technique is created with the use of the homotopy analysis method (HAM), the homotopy polynomial, and the Laplace transformation. Additionally, the existence and uniqueness of the solution are considered, and stability analysis is given by the fixed-point theory (FPT) of the HBV model. Through MATLAB21, the obtained solutions are graphically simulated. The graphical solutions demonstrated that the peak of viral propagation is reduced when a fractional-order derivative is included to the model, and cell damage is minimized by starting treatment early on; however, the disease takes longer to be completely eradicated. The outcomes will be beneficial in the medical field. The fractional model lets us draw significant information essential for predicting disease outcomes and planning appropriate clinical management for patients.

An analytical approach of applying the Lyapunov direct method to polynomial differential systems with discrete time delays

The Lyapunov direct method is a common and effective tool for discussing the global stability of dynamical systems. In this paper, we propose an analytical approach to apply this method for the global stability of the positive equilibrium of a polynomial differential system with discrete time delays, which includes how to construct an applicable Lyapunov functional and to verify the negative (semi-)definiteness of its derivative. Here the linear combination of the Volterra-type functions/functionals and their integrals plays an important role. Moreover, when the delayed system also has a boundary equilibrium, we show that the Lyapunov functional for the global stability of the positive equilibrium can be reformulated to establish the global stability of the boundary equilibrium. As an illustration, we apply this approach to a virus infection model with two delays.

Ectopic expression of murine CD163 enables cell-culture isolation of lactate dehydrogenase-elevating virus 63 years after its discovery.

Mouse models of viral infection play an especially large role in virology. In 1960, a mouse virus, lactate dehydrogenase-elevating virus (LDV), was discovered and found to have the peculiar ability to evade clearance by the immune system, enabling it to persistently infect an individual mouse for its entire lifespan without causing overt disease. However, researchers were unable to grow LDV in culture, ultimately resulting in the demise of this system as a model of failed immunity. We solve this problem by identifying the cell-surface molecule CD163 as the critical missing component in cell-culture systems, enabling the growth of LDV in immortalized cell lines for the first time. This advance creates abundant opportunities for further characterizing LDV in order to study both failed immunity and the family of viruses to which LDV belongs, Arteriviridae (aka, arteriviruses).

Dynamical analysis of a degenerate and time delayed virus infection model with spatial heterogeneity

AbstractThis paper is concerned with a degenerate and time delayed virus infection model with spatial heterogeneity and general incidence. The well‐posedness of the system, including global existence, uniqueness, and ultimately boundedness of the solutions, as well as the existence of a global attractor, is discussed. The basic reproduction number is defined and a characterization of is presented. Without the compactness of the solution semiflow, we establish the global dynamics of the system based on . In addition, when the system is spatially homogeneous, the unique infection steady state is globally asymptotically stable. Simulations are presented to illustrate our theoretical results.

Partially Hydrolyzed Guar Gum Intake Supports the Gut Microbiota and Attenuates Inflammation during Influenza H1N1 Virus Infection in Mice.

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber that is effective for defecation control. It influences the gut microbiota, by which it is metabolized to yield short-chain fatty acids (SCFAs), and it was also recently shown to protect against influenza infection in humans. We here investigated the effects of PHGG in a mouse model of influenza H1N1 virus infection. Eight-week-old C57BL/6 mice were fed normal chow with or without PHGG (500 mg/kg per day) for 4 weeks, infected with H1N1 at 10 weeks of age, and analyzed at 12 weeks of age. Administration of PHGG attenuated the decline in body weight induced by H1N1 infection without affecting food intake. It also ameliorated intestinal atrophy and increased the production of SCFAs including acetic acid, propionic acid, and butyric acid in the cecum, thereby preventing the inhibitory effect of H1N1 infection on SCFA production. The H1N1-induced increases in the serum concentrations of inflammatory cytokines including interferon-γ and interleukin-6 and anti-inflammatory cytokine such as interleukin-10 were all inhibited by PHGG intake. In addition, PHGG administration attenuated inflammatory gene expression in the lung and promoted both natural killer cell activity and regulatory T-cell differentiation in the spleen. Our findings suggest that the consumption of PHGG may improve the gut environment and thereby limit the inflammatory response to H1N1 infection. They may thus provide the basis for novel dietary intervention strategies to suppress the excessive inflammation associated with virus infection.

SARS-COV-2 protein NSP9 promotes cytokine production by targeting TBK1.

SARS-COV-2 infection-induced excessive or uncontrolled cytokine storm may cause injury of host tissue or even death. However, the mechanism by which SARS-COV-2 causes the cytokine storm is unknown. Here, we demonstrated that SARS-COV-2 protein NSP9 promoted cytokine production by interacting with and activating TANK-binding kinase-1 (TBK1). With an rVSV-NSP9 virus infection model, we discovered that an NSP9-induced cytokine storm exacerbated tissue damage and death in mice. Mechanistically, NSP9 promoted the K63-linked ubiquitination and phosphorylation of TBK1, which induced the activation and translocation of IRF3, thereby increasing downstream cytokine production. Moreover, the E3 ubiquitin ligase Midline 1 (MID1) facilitated the K48-linked ubiquitination and degradation of NSP9, whereas virus infection inhibited the interaction between MID1 and NSP9, thereby inhibiting NSP9 degradation. Additionally, we identified Lys59 of NSP9 as a critical ubiquitin site involved in the degradation. These findings elucidate a previously unknown mechanism by which a SARS-COV-2 protein promotes cytokine storm and identifies a novel target for COVID-19 treatment.

A Mouse Model of MHV-1 Virus Infection for Study of Acute and Long COVID Infection.

COVID-19, caused by SARS-CoV-2, has had a significant global impact. While vaccines and treatments have reduced severe cases and deaths, the long-term effects are not yet well understood. Current models used for research, such as non-human primates and transgenic mice, are expensive and require scarce Biosafety Level-3 (BSL-3) laboratories, thereby limiting their practicality. However, the mouse hepatitis virus 1 (MHV-1) mouse model offers a promising alternative. This surrogate model can be investigated in more widely available Biosafety Level-2 (BSL-2) laboratories. Furthermore, mice are affordable and easy to handle, and utilizing MHV-1 as a surrogate for SARS-CoV-2 eliminates the need for costly transgenic mice. Importantly, the MHV-1 model successfully recapitulates COVID-19-related clinical symptoms, weight loss, multiorgan pathological changes and failure in acute stages, irreversible neurological complications, and other long-term organ dysfunction post-infection, which are similar to available human data post-COVID-19. To assist researchers in establishing and using the MHV-1 mouse model, this protocol offers comprehensive guidance encompassing procedures for animal preparation, induction of viral infection, clinical observation, pathological changes, and tissue analysis for mechanistic studies, thereby yielding valuable insights into disease mechanisms and progression. By adopting the MHV-1 model and the provided protocols, researchers can effectively circumvent financial constraints and the limited availability of BSL-3 laboratories, thus facilitating a more accessible and cost-effective approach to investigating the underlying mechanisms of SARS-CoV-2 pathophysiology and exploring potential therapeutic interventions. © 2023 Wiley Periodicals LLC. Basic Protocol: Induction of mouse hepatitis virus 1 (MHV-1) infection in A/J mice Support Protocol 1: Histological evaluation Support Protocol 2: Liver enzyme measurement Support Protocol 3: Western blot analysis of aquaporin expression Support Protocol 4: mRNA measurement Support Protocol 5: Immunohistochemistry/immunofluorescence Support Protocol 6: Tissue water measurement.

Stationary distribution of a reaction-diffusion hepatitis B virus infection model driven by the Ornstein-Uhlenbeck process.

A reaction-diffusion hepatitis B virus (HBV) infection model based on the mean-reverting Ornstein-Uhlenbeck process is studied in this paper. We demonstrate the existence and uniqueness of the positive solution by constructing the Lyapunov function. The adequate conditions for the solution's stationary distribution were described. Last but not least, the numerical simulation demonstrated that reversion rates and noise intensity influenced the disease and that there was a stationary distribution. It was concluded that the solution tends more toward the stationary distribution, the greater the reversion rates and the smaller the noise.

Homotopy decomposition method to analysis fractional hepatitis B virus infection model

Mathematical models have been employed to investigate the factors that govern the progression of infectious diseases in viral infections. This article investigates a fractionalised model for hepatitis B virus infection, curing infected cells. We analysed the fractional hepatitis B virus infection model using the homotopy decomposition method (HDM). Additionally, the existence and uniqueness of the fractional model are considered. The graphical solutions depicted that when introducing a fractional-order derivative to the model, the peak of viral propagation is reduced, and cell damage is minimised by initiating treatment at an early stage; however, the disease takes a longer time to be eradicated. The outcomes may also be valuable in the fields of clinical science and medicine. This model provided insights into the natural history of HBV infection, including the different stages of infection (acute, chronic, and resolved) and the likelihood of progression from one stage to another. This information is essential for predicting disease outcomes and planning appropriate clinical management for patients.

Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model

BackgroundDuring infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and are highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, data are sparsely available on the involvement of NETs in secondary events after virus clearance, which can lead to persistent lung damage and postacute sequelae with chronic fatigue and dyspnea. ObjectivesThis study focuses on late-phase events using a murine model of viral lung infection with postacute sequelae after virus resolution. MethodsC57BL/6JRj mice were infected intranasally with the betacoronavirus murine coronavirus (MCoV, strain MHV-A95), and tissue samples were collected after 2, 4, and 10 days. For NET modulation, mice were pretreated with OM-85 or GSK484 and DNase I were administered intraperitoneally between days 2 to 5 and days 4 to 7, respectively. ResultsRapid, platelet-attributed thrombus formation was followed by a second, late phase of thromboinflammation. This phase was characterized by negligible virus titers but pronounced tissue damage, apoptosis, oxidative DNA damage, and presence of NETs. Inhibition of NETs during the acute phase did not impact virus burden but decreased lung cell apoptosis by 67% and oxidative stress by 94%. Prevention of neutrophil activation by immune training before virus infection reduced damage by 75%, NETs by 31%, and pulmonary thrombi by 93%. ConclusionNETs are detrimental inducers of tissue damage during respiratory virus infection but do not contribute to virus clearance.

Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells.

Major histocompatibility complex (MHC) II is dynamically expressed on mucosal epithelial cells and is induced in response to inflammation and parasitic infections, upon exposure to microbiota, and is increased in chronic inflammatory diseases. However, the regulation of epithelial cell-specific MHC II during homeostasis is yet to be explored. We discovered a novel role for IL-22 in suppressing epithelial cell MHC II partially via the regulation of endoplasmic reticulum (ER) stress, using animals lacking the interleukin-22-receptor (IL-22RA1), primary human and murine intestinal and respiratory organoids, and murine models of respiratory virus infection or with intestinal epithelial cell defects. IL-22 directly downregulated interferon-γ-induced MHC II on primary epithelial cells by modulating the expression of MHC II antigen A α (H2-Aα) and Class II transactivator (Ciita), a master regulator of MHC II gene expression. IL-22RA1-knockouts have significantly higher MHC II expression on mucosal epithelial cells. Thus, while IL-22-based therapeutics improve pathology in chronic disease, their use may increase susceptibility to viral infections.

Approaches for timeline reductions in pathogenesis studies using genetically modified mice.

Although genetically modified mouse models have long been a powerful tool for microbiology research, the manipulation of the mouse genome is expensive, time consuming, and has historically remained the domain of dedicated animal facilities. The recent use of in vivo clustered regularly interspaced short palindromic repeats (CRISPR)-based editing technology has been reported to reduce the expertise, cost, and time required to generate novel mouse lines; it has remained unclear, however, if this new technology could meaningfully alter experimental timelines. Here, we report the optimization of an in oviduct murine genetic manipulation technique for use by microbiologists. We use this approach to generate a series of knockout mice and detail a protocol using an influenza A virus infection model to test the preliminary importance of a host factor in as short as 11 weeks (with a fully backcrossed knockout line in ~22 weeks) from initiation of the study. Broader use of this approach by the microbiology community will allow for more efficient, and rapid, definition of novel pathogenic mechanisms in vivo. IMPORTANCE Clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies have already begun to revolutionize biomedical science. An emerging application of this technology is in the development of genetically modified model organisms to study the mechanisms underlying infectious disease. Here, we describe a protocol using an in vivo CRISPR-based approach that can be used to test the importance of a candidate host factor for microbial pathogenesis in less than 3 months and before complete establishment of a new mouse line. Adoption of this approach by the broader microbiology community will help to decrease the resources and time required to understand how pathogens cause disease which will ultimately speed up the development of new clinical interventions and therapies.

Genetic characterization of duck hepatitis B viruses from Anhui Province, China.

Duck hepatitis B virus (DHBV) infection model was frequently used as the experimental model for human hepatitis B virus (HBV) research. In order to decipher the genetic characteristics of DHBVs from Anhui province of China, 120 duck liver tissue samples were collected and subjected to PCR screening, and 28 samples were detected as DHBV positive. Subsequently, five DHBV-positive samples were selected for genome-wide amplification and a comprehensive analysis. Comparative analysis of complete genome sequences using the MegAlign program showed that five strains of DHBVs shared 94.5-96.3% with each other and 93.2-98.7% with other reference strains in GenBank. The phylogenetic analysis showed that all five DHBV strains belonged to the evolutionary branch of "Chinese DHBV" isolates or DHBV-2. Importantly, three potential intra-genotypic recombination events, between strains AAU-6 and Guilin, strains AAU-1 and GD3, and strains AAU-6 and AAU-1, were respectively found using the RDP and SimPlot softwares and considered the first report in avihepadnaviruses. These results not only improve our understanding for molecular prevalence status of DHBV among ducks, but also provide a reference for recombination mechanism of HBV.

Clinical and Immunologic Correlates of Vasodilatory Shock Among Ebola Virus-Infected Nonhuman Primates in a Critical Care Model.

Existing models of Ebola virus infection have not fully characterized the pathophysiology of shock in connection with daily virologic, clinical, and immunologic parameters. We implemented a nonhuman primate critical care model to investigate these associations. Two rhesus macaques received a target dose of 1000 plaque-forming units of Ebola virus intramuscularly with supportive care initiated on day 3. High-dimensional spectral cytometry was used to phenotype neutrophils and peripheral blood mononuclear cells daily. We observed progressive vasodilatory shock with preserved cardiac function following viremia onset on day 5. Multiorgan dysfunction began on day 6 coincident with the nadir of circulating neutrophils. Consumptive coagulopathy and anemia occurred on days 7 to 8 along with irreversible shock, followed by death. The monocyte repertoire began shifting on day 4 with a decline in classical and expansion of double-negative monocytes. A selective loss of CXCR3-positive B and T cells, expansion of naive B cells, and activation of natural killer cells followed viremia onset. Our model allows for high-fidelity characterization of the pathophysiology of acute Ebola virus infection with host innate and adaptive immune responses, which may advance host-targeted therapy design and evaluation for use after the onset of multiorgan failure.

Stability analysis and optimal control strategies of a fractional-order monkeypox virus infection model

In this study, the spread of the monkeypox virus is investigated through the dynamical study of a novel Caputo fractional order monkeypox epidemic model. The interaction between human and rodent populations along with the effects of control signals are considered in the model. These control signals are established through the optimal control strategy. Furthermore, the effect of memory is examined via varying fractional order parameters in the model. The influences of other parameters are also examined. The positivity and boundness of the solution are verified through theoretical analysis. In addition, the equilibrium points for the system are obtained for both the free and endemic cases, and the local stability has been studied. To verify the theoretical findings, numerical experiments are conducted. The optimal control signals are obtained and verified through numerical simulations of different configurations of control parameters. From these simulations, it is found that the optimal control scheme can help in reducing the size of the infected, quarantined, and exposed categories while increasing the susceptible and recovered categories. These acquired results can provide some assistance to governments in providing some preventive control to suppress the spread of the virus.

Mathematical analysis of a multiscale hepatitis C virus infection model with two viral strains

Direct-acting antiviral agents (DAAs) have shown higher cure rates for treating hepatitis C virus (HCV) by directly interfering with different steps of the HCV life cycle. To optimize drug combinations and accurately quantify the antiviral effect of DAAs treatments, mathematical models should include the intracellular virus replication processes. In this study, we develop a two-strain multiscale age-structured model that includes intracellular viral RNA replication and extracellular viral infection. We prove the existence, positivity, and boundedness of the solution, and derive the conditions for the existence and stability of the three steady states (non-infection steady state, boundary steady state, and coexistence steady state). Under certain biologically reasonable assumptions, we obtain the approximate solutions of the viral load decline of the two virus strains (sensitive and drug-resistant virus strains) during treatment, and the long-term approximation is shown to be in good agreement with the solution of the original model. We also carry out numerical simulations using the long-term approximate solution, providing insights into the influence of antiviral effects on the viral load change of the two virus strains during treatment with DAAs.