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Current medical research suggests that latently infected cells are the primary source of the virus's resistance to elimination. Moreover, these cells can participate in cell–cell transmission. Human immunodeficiency virus type 1 (HIV-1) can transmit to CD4 + T cells by three transmission modes, cell-free, latent cell–cell and active cell–cell. Incorporating the effect of latent infection, weakened humoral and CTL responses as well as three transmission modes, we investigate two generalized HIV-1 dynamics models. Three general incidence functions are used to represent the three viral transmission modes. Our proposed models extend and generalize many viral infection models presented in the virology literature. We begin by demonstrating the solutions' boundedness and nonnegativity which guarantee the model's wellposedness. We calculate the model's basic reproduction ratio (ℜ 0). We establish that the model admits two steady-states, namely, virus-free steady-state and virus-persistence steady-state. Through application of Lyapunov's approach and LaSalle's invariance principle, we demonstrate the global stability of each state-state. For two special forms of the general incidence functions, Holling type-II incidence and Crowley–Martin incidence, we provide numerical simulations to validate our theoretical findings. We illustrate how time delay and weakened adaptive immunity affect HIV-1 dynamics. More specifically, numerical data support our theoretical conclusions on the stability of steady-states. To demonstrate the impact of the parameter values on ℜ 0 , we examine the sensitivity analysis. We have demonstrated that each of the three viral transmission modes adds to ℜ 0 , and that ℜ 0 would be underestimated if any one of them were ignored. This might lead to inadequate medication effectiveness that aims to remove the viruses from the body. The effects of weakened adaptive immunity and time delay on HIV-1 progression are examined. As per our findings, reduced adaptive immunity plays a crucial role in the proliferation of the infection. Weaken adaptive immunity can lead to the acquired immune deficiency syndrome (AIDS) and give a chance for opportunistic infections. We showed that ℜ 0 fall as a function of both medication efficacy and delay parameter. If a model with time delays is used, fewer treatment efficacies will be required to maintain the system at the virus-free steady-state and eradicate HIV-1 from the body. Our study's findings can help us better understand HIV-1 dynamics in the host and can also guide the development of new pharmacological therapies. [ABSTRACT FROM AUTHOR]

Current medical research suggests that latently infected cells are the primary source of the virus’s resistance to elimination. Moreover, these cells can participate in cell–cell transmission. Human immunodeficiency virus type 1 (HIV-1) can transmit to CD4+T cells by three transmission modes, cell-free, latent cell–cell and active cell–cell. Incorporating the effect of latent infection, weakened humoral and CTL responses as well as three transmission modes, we investigate two generalized HIV-1 dynamics models. Three general incidence functions are used to represent the three viral transmission modes. Our proposed models extend and generalize many viral infection models presented in the virology literature. We begin by demonstrating the solutions’ boundedness and nonnegativity which guarantee the model’s wellposedness. We calculate the model’s basic reproduction ratio (ℜ0). We establish that the model admits two steady-states, namely, virus-free steady-state and virus-persistence steady-state. Through application of Lyapunov’s approach and LaSalle’s invariance principle, we demonstrate the global stability of each state-state. For two special forms of the general incidence functions, Holling type-II incidence and Crowley–Martin incidence, we provide numerical simulations to validate our theoretical findings. We illustrate how time delay and weakened adaptive immunity affect HIV-1 dynamics. More specifically, numerical data support our theoretical conclusions on the stability of steady-states. To demonstrate the impact of the parameter values on ℜ0, we examine the sensitivity analysis. We have demonstrated that each of the three viral transmission modes adds to ℜ0, and that ℜ0 would be underestimated if any one of them were ignored. This might lead to inadequate medication effectiveness that aims to remove the viruses from the body. The effects of weakened adaptive immunity and time delay on HIV-1 progression are examined. As per our findings, reduced adaptive immunity plays a crucial role in the proliferation of the infection. Weaken adaptive immunity can lead to the acquired immune deficiency syndrome (AIDS) and give a chance for opportunistic infections. We showed that ℜ0 fall as a function of both medication efficacy and delay parameter. If a model with time delays is used, fewer treatment efficacies will be required to maintain the system at the virus-free steady-state and eradicate HIV-1 from the body. Our study’s findings can help us better understand HIV-1 dynamics in the host and can also guide the development of new pharmacological therapies.

This research aims to formulate and analyze two mathematical models describing the within-host dynamics of human immunodeficiency virus type-1 (HIV-1) in case of impaired humoral immunity. These models consist of five compartments, including healthy CD4 + T cells, (HIV-1)-latently infected cells, (HIV-1)-actively infected cells, HIV-1 particles, and B-cells. We make the assumption that healthy cells can become infected when exposed to: (i) HIV-1 particles resulting from viral infection (VI), (ii) (HIV-1)-latently infected cells due to latent cellular infection (CI), and (iii) (HIV-1)-actively infected cells due to active CI. In the second model, we introduce distributed time-delays. For each of these systems, we demonstrate the non-negativity and boundedness of the solutions, calculate the basic reproductive number, identify all possible equilibrium states, and establish the global asymptotic stability of these equilibria. We employ the Lyapunov method in combination with LaSalle's invariance principle to investigate the global stability of these equilibrium points. Theoretical findings are subsequently validated through numerical simulations. Additionally, we explore the impact of B-cell impairment, time-delays, and CI on HIV-1 dynamics. Our results indicate that weakened immunity significantly contributes to disease progression. Furthermore, the presence of time-delays can markedly decrease the basic reproductive number, thereby suppressing HIV-1 replication. Conversely, the existence of latent CI spread increases the basic reproductive number, intensifying the progression of HIV-1. Consequently, neglecting latent CI spread in the HIV-1 dynamics model can lead to an underestimation of the basic reproductive number, potentially resulting in inaccurate or insufficient drug therapies for eradicating HIV-1 from the body. These findings offer valuable insights that can enhance the understanding of HIV-1 dynamics within a host. [ABSTRACT FROM AUTHOR]

In order to investigate the impact of general nonlinear incidence, cellular infection, and multiple time delays on the dynamical behaviors of a virus infection model, a within-host model describing the virus infection is formulated and studied by taking these factors into account in a single model. Qualitative analysis of the global properties of the equilibria is carried out by utilizing the methods of Lyapunov functionals. The existence and properties of local and global Hopf bifurcations are discussed by regarding immune delay as the bifurcation parameter via the normal form, center manifold theory, and global Hopf bifurcation theorem. This work reveals that the immune delay is mainly responsible for the existence of the Hopf bifurcation and rich dynamics rather than the intracellular delays, and the general nonlinear incidence does not change the global stability of the equilibria. Moreover, ignoring the cell-to-cell infection may underevaluate the infection risk. Numerical simulations are carried out for three kinds of incidence function forms to show the rich dynamics of the model. The bifurcation diagrams and the identification of the stability region show that increasing the immune delay can destabilize the immunity-activated equilibrium and induce a Hopf bifurcation, stability switches, and oscillation solutions. The obtained results are a generalization of some existing models. [ABSTRACT FROM AUTHOR]

This research aims to formulate and analyze two mathematical models describing the within-host dynamics of human immunodeficiency virus type-1 (HIV-1) in case of impaired humoral immunity. These models consist of five compartments, including healthy CD4+ T cells, (HIV-1)-latently infected cells, (HIV-1)-actively infected cells, HIV-1 particles, and B-cells. We make the assumption that healthy cells can become infected when exposed to: (i) HIV-1 particles resulting from viral infection (VI), (ii) (HIV-1)-latently infected cells due to latent cellular infection (CI), and (iii) (HIV-1)-actively infected cells due to active CI. In the second model, we introduce distributed time-delays. For each of these systems, we demonstrate the non-negativity and boundedness of the solutions, calculate the basic reproductive number, identify all possible equilibrium states, and establish the global asymptotic stability of these equilibria. We employ the Lyapunov method in combination with LaSalle’s invariance principle to investigate the global stability of these equilibrium points. Theoretical findings are subsequently validated through numerical simulations. Additionally, we explore the impact of B-cell impairment, time-delays, and CI on HIV-1 dynamics. Our results indicate that weakened immunity significantly contributes to disease progression. Furthermore, the presence of time-delays can markedly decrease the basic reproductive number, thereby suppressing HIV-1 replication. Conversely, the existence of latent CI spread increases the basic reproductive number, intensifying the progression of HIV-1. Consequently, neglecting latent CI spread in the HIV-1 dynamics model can lead to an underestimation of the basic reproductive number, potentially resulting in inaccurate or insufficient drug therapies for eradicating HIV-1 from the body. These findings offer valuable insights that can enhance the understanding of HIV-1 dynamics within a host.

Human β-defensin 3 (hBD3) is an antimicrobial peptide and a chemoattractant molecule expressed in human keratinocytes. Lysates prepared from Lactoplantibacillus plantarum KG (KG lysates), a fermented lactobacillus strain with Ginseng extracts, significantly induced hBD3 in human keratinocytes. hBD3 induced by KG lysates affected the internalization of Staphylococcus aureus by human keratinocytes. The intracellular pathway for the induction of hBD3 by KG lysates was examined using inhibitors. Briefly, KG lysates stimulated the late signaling pathway including JAK1/2, which might be induced by the EGFR- or IFN-γ-mediated pathway, and affected hBD3 induction. Through this study, we confirmed that KG lysates have the ability to control bacterial infections, especially S. aureus, in human keratinocytes. Thus, KG lysates can be provided in various formulations for the development of food and pharmaceutical materials to control bacterial infection. [ABSTRACT FROM AUTHOR]

In order to investigate the impact of general nonlinear incidence, cellular infection, and multiple time delays on the dynamical behaviors of a virus infection model, a within-host model describing the virus infection is formulated and studied by taking these factors into account in a single model. Qualitative analysis of the global properties of the equilibria is carried out by utilizing the methods of Lyapunov functionals. The existence and properties of local and global Hopf bifurcations are discussed by regarding immune delay as the bifurcation parameter via the normal form, center manifold theory, and global Hopf bifurcation theorem. This work reveals that the immune delay is mainly responsible for the existence of the Hopf bifurcation and rich dynamics rather than the intracellular delays, and the general nonlinear incidence does not change the global stability of the equilibria. Moreover, ignoring the cell-to-cell infection may underevaluate the infection risk. Numerical simulations are carried out for three kinds of incidence function forms to show the rich dynamics of the model. The bifurcation diagrams and the identification of the stability region show that increasing the immune delay can destabilize the immunity-activated equilibrium and induce a Hopf bifurcation, stability switches, and oscillation solutions. The obtained results are a generalization of some existing models.

Oral mouthwashes decrease the infectivity of several respiratory viruses including SARS-CoV-2. However, the precise agents with antiviral activity in these oral rinses and their exact mechanism of action remain unknown. Here we show that cetylpyridinium chloride (CPC), a quaternary ammonium compound in many oral mouthwashes, reduces SARS-CoV-2 infectivity by inhibiting the viral fusion step with target cells after disrupting the integrity of the viral envelope. We also found that CPC-containing mouth rinses decreased more than a thousand times the infectivity of SARS-CoV-2 in vitro, while the corresponding vehicles had no effect. This activity was effective for different SARS-CoV-2 variants, including the B.1.1.7 or Alpha variant originally identified in United Kingdom, and in the presence of sterilized saliva. CPC-containing mouth rinses could therefore represent a cost-effective measure to reduce SARS-CoV-2 infectivity in saliva, aiding to reduce viral transmission from infected individuals regardless of the variants they are infected with. [ABSTRACT FROM AUTHOR]

Human β-defensin 3 (hBD3) is an antimicrobial peptide and a chemoattractant molecule expressed in human keratinocytes. Lysates prepared from Lactoplantibacillus plantarum KG (KG lysates), a fermented lactobacillus strain with Ginseng extracts, significantly induced hBD3 in human keratinocytes. hBD3 induced by KG lysates affected the internalization of Staphylococcus aureus by human keratinocytes. The intracellular pathway for the induction of hBD3 by KG lysates was examined using inhibitors. Briefly, KG lysates stimulated the late signaling pathway including JAK1/2, which might be induced by the EGFR- or IFN-γ-mediated pathway, and affected hBD3 induction. Through this study, we confirmed that KG lysates have the ability to control bacterial infections, especially S. aureus, in human keratinocytes. Thus, KG lysates can be provided in various formulations for the development of food and pharmaceutical materials to control bacterial infection.

This paper studies the global stability of pathogen dynamics model with pathogen-to-cell and cell-to-cell transmissions. We consider three types of time delays and two types of infected cells, latent and active. The model is given by a system of nonlinear delay differential equations which is discretized by utilizing nonstandard finite difference scheme. Positivity and boundedness properties of the solutions are proven. Global stability of the equilibria is established by constructing Lyapunov functions and applying LaSalle's invariance principle. [ABSTRACT FROM AUTHOR]

In this article, we examine the dynamics of a Chikungunya virus (CHIKV) infection model with two routes of infection. The model uses four categories, namely, uninfected cells, infected cells, the CHIKV virus, and antibodies. The equilibrium points of the model, which consist of the free point for the CHIKV and CHIKV endemic point, are first analytically determined. Next, the local stability of the equilibrium points is studied, based on the basic reproduction number (R0) obtained by the next-generation matrix. From the analysis, it is found that the disease-free point is locally asymptotically stable if R0≤1, and the CHIKV endemic point is locally asymptotically stable if R0>1. Using the Lyapunov method, the global stability analysis of the steady-states confirms the local stability results. We then describe our design of an optimal recruitment strategy to minimize the number of infected cells, as well as a nonlinear optimal control problem. Some numerical simulations are provided to visualize the analytical results obtained.

Abstract Listeriosis is a severe disease caused by the opportunistic bacterial pathogen Listeria monocytogenes (L. monocytogenes). Previous studies indicate that of the four phylogenetical lineages known, lineage I strains are significantly more prevalent in clinical infections than in the environment. Among lineage 1, sequence type (ST1) belongs to the most frequent genotypes in clinical infections and behaves hyperinvasive in experimental in vitro infections compared to lineage II strains suggesting that yet uncharacterized virulence genes contribute to high virulence of certain lineage I strains. This study investigated the effect of four specific lineage I genes encoding surface proteins with internalin‐like structures on cellular infection. CNS derived cell lines (fetal bovine brain cells, human microglia cells) and non‐CNS derived cell lines (bovine macrophage cells, human adenocarcinoma cells) that represent the various target cells of L. monocytogenes were infected with the parental ST1 strain and deletion mutants of the four genes. Despite their association with lineage I, deletion of the four genes investigated did not dampen the hyperinvasiveness of the ST1 strain. Similarly, these genes did not contribute to the intracellular survival and intercellular spread of L. monocytogenes ST1, indicating that these genes may have other functions, either during the infection process or outside the host.

We have developed a class of viral infection model with cell-to-cell transmission and humoral immune response. The model addresses both immune and intracellular delays. We also constructed Lyapunov functionals to establish the global dynamical properties of the equilibria. Theoretical results indicate that considering only two intracellular delays did not affect the dynamical behavior of the model, but incorporating an immune delay greatly affects the dynamics, i.e. an immune delay may destabilize the immunity-activated equilibrium and lead to Hopf bifurcation, oscillations and stability switches. Our results imply that an immune delay dominates the intracellular delays in the model. We also investigated the direction of the Hopf bifurcation and the stability of the periodic solutions by applying normal form and center manifold theory, and investigated the existence of global Hopf bifurcation by regarding the immune delay as a bifurcation parameter. Numerical simulations are carried out to support the analytical conclusions. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is among the best-characterized intracellular pathogens. Its virulence factors, and the way they interfere with host cells to hijack host functions and promote the establishment and dissemination of the infection, have been the focus of multiple studies over the last 30 years. During cellular infection, L. monocytogenes was shown to induce host DNA damage and delay the host cell cycle to its own benefit. However, whether the cell cycle stage would interfere with the capacity of Listeria to infect human cultured cell lines was never assessed. We found here that L. monocytogenes preferentially infects cultured cells in G2/M phases. Inside G2/M cells, the bacteria lead to an increase in the overall mitosis duration by delaying the mitotic exit. We showed that L. monocytogenes infection causes a sustained activation of the spindle assembly checkpoint, which we correlated with the increase in the percentage of misaligned chromosomes detected in infected cells. Moreover, we demonstrated that chromosome misalignment in Listeria-infected cells required the function of two Listeria virulence factors, ActA and InlC. Our findings show the pleiotropic role of Listeria virulence factors and their cooperative action in successfully establishing the cellular infection.

The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.

The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression. [ABSTRACT FROM AUTHOR]

Bacteria of the Brucella genus are responsible for brucellosis, a worldwide zoonosis. These bacteria are known to have a peculiar intracellular trafficking, with a first long and non-proliferative endosomal stage and a second proliferation stage, often associated with its localization of the bacteria in the endoplasmic reticulum (ER). However, the status of the bacterial cell cycle during the non-proliferative phase was still unknown. In a recent study [Nat. Communic. 5:4366], we followed the cell cycle of B. abortus in culture and inside the host cells. In culture, B. abortus initiates the replication of its large chromosome before the small chromosome. The origin and terminator regions of these two chromosomes display distinct localization and dynamics within B. abortus. In HeLa cells and RAW264.7 macrophages, the bacteria in G1 (i.e. before the initiation of chromosomes replication) are preferentially found during the endosomal stage of the infection. During this period, growth is also arrested. The cell cycle arrest and resume during the B. abortus trafficking in host cell suggest that like the model Alphaproteobacterium Caulobacter crescentus, these bacteria are able to block their cell cycle at the G1 phase when starvation is sensed.

Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global becoming a new worldwide challenge. For more than a century since its discovery, it has remained neglected with no effective drugs or vaccines. The mechanisms by which Trypanosoma cruzi regulates and uses the extracellular matrix (ECM) to invade cells and cause disease are just beginning to be understood. Here we critically review and discuss the regulation of the ECM interactome by T. cruzi, the use of the ECM by T. cruzi and analyze the molecular ECM/T. cruzi interphase during the early process of infection. It has been shown that invasive trypomastigote forms of T. cruzi use and modulate components of the ECM during the initial process of infection. Infective trypomastigotes up-regulate the expression of laminin γ-1 (LAMC1) and thrombospondin (THBS1) to facilitate the recruitment of trypomastigotes to enhance cellular infection. Silencing the expression of LAMC1 and THBS1 by stable RNAi dramatically reduces try-panosome infection.T. cruzi gp83, a ligand that mediates the attachment of trypanosomes to cells to initiate infection, up-regulates LAMC1 expression to enhance cellular infection. Infective trypomastigotes use Tc85 to interact with laminin, p45 mucin to interact with LAMC1 through galectin-3 (LGALS3), a human lectin, and calreticulin (TcCRT) to interact with TSB1 to enhance cellular infection. Silencing the expression of LGALS3 also reduces cellular infection. Despite the role of the ECM inT. cruzi infection, almost nothing is known about the ECM interactome networks operating in the process of T. cruzi infection and its ligands. Here, we present the first elucidation of the human ECM interactome network regulated by T. cruzi and its gp83 ligand that facilitates cellular infection. The elucidation of the human ECM interactome regulated by T. cruzi and the dissection of the molecular ECM/T. cruzi interphase using systems biology approaches are not only critically important for the understanding of the molecular pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease [ABSTRACT FROM AUTHOR]

Abstract: Brucella is a broad-range, facultative intracellular pathogen that can survive and replicate in an endoplasmic reticulum (ER)-derived replication niche by preventing fusion of its membrane-bound compartment with late endosomes and lysosomes. This vacuolar hijacking was demonstrated to be dependent on the type IV secretion system VirB but no secreted effectors have been identified yet. A virB mutant is unable to reach its ER-derived replicative niche and does not multiply intracellularly. In this paper, we showed that, by co-infecting bovine macrophages or HeLa cells with the wild type (WT) strain of Brucella melitensis 16M and a deletion mutant of the complete virB operon, the replication of ΔvirB is rescued in almost 20% of the co-infected cells. Furthermore, we demonstrated that co-infections with the WT strains of Brucella abortus or Brucella suis were equally able to rescue the replication of the B. melitensis ΔvirB mutant. By contrast, no rescue was observed when the WT strain was given 1h before or after the infection with the ΔvirB mutant. Finally, vacuoles containing the rescued ΔvirB mutant were shown to exclude the LAMP-1 marker in a way similar to the WT containing vacuoles. [Copyright &y& Elsevier]

Abstract: Interactions between Trypanosoma cruzi and the extracellular matrix play an important role in cellular invasion. Here we show that T. cruzi increases the levels of thrombospondin-1 (TSP-1) expression in host cells during early infection. Stable RNA interference of host cell TSP-1 knocks down the levels of TSP-1 transcripts and protein expression in mammalian cells causing inhibition of T. cruzi infection. Addition of TSP-1 to these cells restores infection. Thus, host TSP-1, regulated by the parasite, plays a crucial role in early infection. This is the first report showing that a human parasite modulates TSP-1 expression to facilitate infection. [Copyright &y& Elsevier]

Abstract: Cellular activation involves the re-organization of receptor molecules and the intracellular signalosom in the cell membrane. Recent studies indicate that specialized domains of the cell membrane, termed rafts, are central for the spatial organization of receptors and signaling molecules. Rafts are converted into larger membrane platforms by activity of the acid sphingomyelinase, which hydrolyses raft-sphingomyelin to ceramide. Ceramide molecules spontaneously associate to form ceramide-enriched microdomains, which fuse to large ceramide-enriched membrane platforms. The acid sphingomyelinase is activated by multiple stimuli including CD95, CD40, DR5/TRAIL, CD20, FcγRII, CD5, LFA-1, CD28, TNF, the Interleukin-1 receptor, the PAF-receptor, CD14, infection with P. aeruginosa, S. aureus, N. gonorrhoeae, Sindbis-Virus, Rhinovirus, treatment with γ-irradiation, UV-light, doxorubicin, cisplatin, disruption of integrin-signaling and under some conditions of developmental death. Ceramide-enriched membrane platforms serve the clustering of receptors, the recruitment of intracellular signaling molecules and the exclusion of inhibitory signaling factors and, thus, facilitate signal transduction initiated by the specific stimulus. [Copyright &y& Elsevier]

In this article, we examine the dynamics of a Chikungunya virus (CHIKV) infection model with two routes of infection. The model uses four categories, namely, uninfected cells, infected cells, the CHIKV virus, and antibodies. The equilibrium points of the model, which consist of the free point for the CHIKV and CHIKV endemic point, are first analytically determined. Next, the local stability of the equilibrium points is studied, based on the basic reproduction number ( R 0 ) obtained by the next-generation matrix. From the analysis, it is found that the disease-free point is locally asymptotically stable if R 0 ≤ 1 , and the CHIKV endemic point is locally asymptotically stable if R 0 > 1 . Using the Lyapunov method, the global stability analysis of the steady-states confirms the local stability results. We then describe our design of an optimal recruitment strategy to minimize the number of infected cells, as well as a nonlinear optimal control problem. Some numerical simulations are provided to visualize the analytical results obtained. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is among the best-characterized intracellular pathogens. Its virulence factors, and the way they interfere with host cells to hijack host functions and promote the establishment and dissemination of the infection, have been the focus of multiple studies over the last 30 years. During cellular infection, L. monocytogenes was shown to induce host DNA damage and delay the host cell cycle to its own benefit. However, whether the cell cycle stage would interfere with the capacity of Listeria to infect human cultured cell lines was never assessed. We found here that L. monocytogenes preferentially infects cultured cells in G2/M phases. Inside G2/M cells, the bacteria lead to an increase in the overall mitosis duration by delaying the mitotic exit. We showed that L. monocytogenes infection causes a sustained activation of the spindle assembly checkpoint, which we correlated with the increase in the percentage of misaligned chromosomes detected in infected cells. Moreover, we demonstrated that chromosome misalignment in Listeria-infected cells required the function of two Listeria virulence factors, ActA and InlC. Our findings show the pleiotropic role of Listeria virulence factors and their cooperative action in successfully establishing the cellular infection. [ABSTRACT FROM AUTHOR]

Chagas disease (American trypanosomiasis) is a 'neglected' pathology that affects millions of people worldwide, mainly in Latin America. Trypanosoma cruzi , the causative agent, is an obligate intracellular parasite with a complex and diverse biology that infects several mammalian species, including humans. Because of genetic variability among strains and the presence of four biochemically and morphologically distinct parasite forms, the outcome of T. cruzi infection varies considerably depending on host cell type and parasite strain. During the initial contact, cellular communication is established by host-recognition-mediated responses, followed by parasite adherence and penetration. For this purpose, T. cruzi expresses a variety of proteins that modify the host cell, enabling it to safely reach the cytoplasm. After entry into the host cell, T. cruzi forms a transitory structure termed 'parasitophorous vacuole' (PV), followed by its cytoplasmic replication and differentiation after PV rupture, and subsequent invasion of other cells. The success of infection, maintenance and survival inside host cells is facilitated by the ability of T. cruzi to subvert various host signaling mechanisms. We focus in this Review on the various mechanisms that induce host cytoskeletal rearrangements, activation of autophagy-related proteins and crosstalk among major immune response regulators, as well as recent studies on the JAK-STAT pathway., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Listeriosis is a severe disease caused by the opportunistic bacterial pathogen Listeria monocytogenes (L. monocytogenes). Previous studies indicate that of the four phylogenetical lineages known, lineage I strains are significantly more prevalent in clinical infections than in the environment. Among lineage 1, sequence type (ST1) belongs to the most frequent genotypes in clinical infections and behaves hyperinvasive in experimental in vitro infections compared to lineage II strains suggesting that yet uncharacterized virulence genes contribute to high virulence of certain lineage I strains. This study investigated the effect of four specific lineage I genes encoding surface proteins with internalin-like structures on cellular infection. CNS derived cell lines (fetal bovine brain cells, human microglia cells) and non-CNS derived cell lines (bovine macrophage cells, human adenocarcinoma cells) that represent the various target cells of L. monocytogenes were infected with the parental ST1 strain and deletion mutants of the four genes. Despite their association with lineage I, deletion of the four genes investigated did not dampen the hyperinvasiveness of the ST1 strain. Similarly, these genes did not contribute to the intracellular survival and intercellular spread of L. monocytogenes ST1, indicating that these genes may have other functions, either during the infection process or outside the host., (© 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes . We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.

Bacterial pathogens often interfere with host tyrosine phosphorylation cascades to control host responses and cause infection. Given the role of tyrosine phosphorylation events in different human infections and our previous results showing the activation of the tyrosine kinase Src upon incubation of cells with Listeria monocytogenes, we searched for novel host proteins undergoing tyrosine phosphorylation upon L. monocytogenes infection. We identify the heavy chain of the non-muscle myosin IIA (NMHC-IIA) as being phosphorylated in a specific tyrosine residue in response to L. monocytogenes infection. We characterize this novel post-translational modification event and show that, upon L. monocytogenes infection, Src phosphorylates NMHC-IIA in a previously uncharacterized tyrosine residue (Tyr-158) located in its motor domain near the ATP-binding site. In addition, we found that other intracellular and extracellular bacterial pathogens trigger NMHC-IIA tyrosine phosphorylation. We demonstrate that NMHC-IIA limits intracellular levels of L. monocytogenes, and this is dependent on the phosphorylation of Tyr-158. Our data suggest a novel mechanism of regulation of NMHC-IIA activity relying on the phosphorylation of Tyr-158 by Src., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Bacteria of the Brucella genus are responsible for brucellosis, a worldwide zoonosis. These bacteria are known to have a peculiar intracellular trafficking, with a first long and non-proliferative endosomal stage and a second proliferation stage, often associated with its localization of the bacteria in the endoplasmic reticulum (ER). However, the status of the bacterial cell cycle during the non-proliferative phase was still unknown. In a recent study [Nat. Communic. 5:4366], we followed the cell cycle of B. abortus in culture and inside the host cells. In culture, B. abortus initiates the replication of its large chromosome before the small chromosome. The origin and terminator regions of these two chromosomes display distinct localization and dynamics within B. abortus . In HeLa cells and RAW264.7 macrophages, the bacteria in G1 (i.e. before the initiation of chromosomes replication) are preferentially found during the endosomal stage of the infection. During this period, growth is also arrested. The cell cycle arrest and resume during the B. abortus trafficking in host cell suggest that like the model Alphaproteobacterium Caulobacter crescentus , these bacteria are able to block their cell cycle at the G1 phase when starvation is sensed., Competing Interests: Conflict of interest: The authors declare no competing financial interests.