Search

The high-risk α-type papillomaviruses have a C-terminal PDZ-binding motif (PBM) on one of the two major oncoproteins E6 or E7; the vast majority on E6. The PBM is essential for the high-risk HPV life cycle, for episomal maintenance of the virus genome, and for maintaining the mitotic stability of the infected cell. The question is why only these viruses have PBMs - are there specific constraints imposed by the mucosal epithelium in which these viruses replicate? However the low-risk α-HPVs, such as HPV-6 and HPV-11 replicate extremely efficiently without a PBM, while viruses of the alpha8 group, such as HPV-40, replicate well with a very primitive PBM. So what does PDZ-binding capacity contribute to the fitness of the virus?

Despite the success of antiretroviral therapy (ART) for people living with HIV, lifelong treatment is required and there is no cure. HIV can integrate in the host genome and persist for the life span of the infected cell. These latently infected cells are not recognized as foreign because they are largely transcriptionally silent, but contain replication-competent virus that drives resurgence of the infection once ART is stopped. With a combination of immune activators, neutralizing antibodies, and therapeutic vaccines, some nonhuman primate models have been cured, providing optimism for these approaches now being evaluated in human clinical trials. In vivo delivery of gene-editing tools to either target the virus, boost immunity or protect cells from infection, also holds promise for future HIV cure strategies. In this Review, we discuss advances related to HIV cure in the last 5 years, highlight remaining knowledge gaps and identify priority areas for research for the next 5 years. An effective and scalable cure strategy is a top priority for the HIV research field; this Review discusses recent advances, knowledge gaps, and priority research areas for the next 5 years.

The stability analysis in this mathematical model was related to the infection of the Coronavirus Disease 2019 (Covid-19). In this mathematical model there were two balance points, namely the point of balance free from Covid-19 and the one infected with Covid-19. The stability of the equilibrium point was influenced by all parameters, i.e. target cells die during each cycle, number of target cells at  = 0, target cells infected during each cycle based on virion unit density, effective surface area of the network, the ratio of the number of virus particles to the number of virions, infected cells die during each cycle, the number of virus particles produced by each infected cell during each cycle, and virus particles die during each cycle. In the simulation model, immunity is divided into high, medium and low immunity. For high, moderate and low immunity, respectively, the highest number of target cells is in high, medium and low immunity, whereas for the number of infected cells and the number of Covid-19, it is in the opposite sequence of the number of target cells.

The field of cellular microbiology, rooted in the co-evolution of microbes and their hosts, studies intracellular pathogens and their manipulation of host cell machinery. In this review, we highlight emerging technologies and infection models that recently promoted opportunities in cellular microbiology. We overview the explosion of microscopy techniques and how they reveal unprecedented detail at the host-pathogen interface. We discuss the incorporation of robotics and artificial intelligence to image-based screening modalities, biochemical mapping approaches, as well as dual RNA-sequencing techniques. Finally, we describe chips, organoids and animal models used to dissect biophysical and in vivo aspects of the infection process. As our knowledge of the infected cell improves, cellular microbiology holds great promise for development of anti-infective strategies with translational applications in human health., Cellular microbiology is a field that combines the study of infection and cell biology. In this review, we highlight emerging technologies and infection models that recently transformed our understanding of the infected cell and may inspire future medicine.

У статті на підставі літературних даних продемонстровано роль клітинних реакцій у розвитку імунної відповіді при пневмонії, спричиненої Staphylococcus aureus. Описано механізми взаємодії Staphylococcus aureus із вродженими лімфоїдними клітинами, Т-лімфоцитами. Наведена порівняльна характеристика рецепторного апарату NK-клітин, описано механізми кiлинга інфікованих клітин iмуноцитами вродженої імунної системи.

Viroporins are involved in viral pathogenesis, play an important role in the morphogenesis of virions and ensure their release from the infected cell. These proteins are potentially promising as possible targets for the regulation of virus reproduction. The literature data on the current understanding of coronavirus viroporins functioning are summarized in the review. Special attention is focused on specific structural features that determine the functional ability of these proteins. The basic principles of viroporins localization in the cell and their influence on the coronavirus life cycle are considered. Keywords: coronavirus, pore formation, protein 3a, protein 8a, protein E, SARS, viroporins

An interesting finding that emerged from the study was the difference in potency between inactivated rabies vaccines prepared in liquid and lyophilized forms. Inactivated rabies vaccine prepared from BHK21 infected cell culture in the two forms revealed that its immunogenicity was completely preserved on lyophilization. The two vaccine formulae were found to be free from foreign contaminants, safe in both inoculated mice and puppies and potent inducing high levels of specific rabies antibodies in vaccinated puppies. Such antibodies were increased gradually from the first-week post-vaccination to the same extent in the blood of immunized puppies with the lyophilized vaccine as in that of puppies immunized with liquid vaccine. These results confirmed the claim that inactivated rabies vaccines could be lyophilized with retention of potency. Considering the possible value of a stable, freeze-dried rabies vaccine that could be stored and transported with ease, it was considered desirable to confirm the above findings.

A fines de diciembre de 2019, un nuevo coronavirus (SARS-CoV-2) fue identificado como el agente causal de una nueva enfermedad respiratoria llamada COVID-19 por la OMS Sus sintomas incluyen fiebre, tos seca y dificultad respiratoria Estos sintomas en general son leves, aunque, pueden ser fatales en adultos mayores y pacientes con comorbilidades Se realizo busqueda bibliografica en Pubmed y Clinical Key donde se seleccionaron 22 articulos de acuerdo con los criterios de inclusion SARS-CoV-2 pertenece al genero de los Betacoronavirus y tiene similitudes genomicas con SARS-CoV y MERS-CoV El virion de SARS-CoV-2 consta de una nucleocapside y de una envoltura externa compuesta por proteinas estructurales principales y accesorias Su material genetico consiste en una cadena de RNA monocatenario de polaridad positiva, en el que, se codifican proteinas importantes para su transcripcion y replicacion El mecanismo de infeccion de SARS-CoV-2 comienza con la union del virion a un receptor (ACE2) de la celula huesped y su posterior entrada por endocitosis El genoma RNA viral se libera al citoplasma donde se transcriben y se traducen las proteinas necesarias para la produccion de las proteinas estructurales y para la replicacion de su material genetico Posteriormente, el RNA replicado se asocia con la nucleocapside y se ensambla junto con las proteinas estructurales para conformar las particulas viricas que seran liberadas de la celula infectada El sistema inmune hace frente a la infeccion viral mediante el reconocimiento de patrones moleculares asociados a patogenos (PAMPs) por parte de la inmunidad innata y por la accion de los linfocitos T y B por parte de la inmunidad humoral El conocimiento de las bases geneticas y moleculares de SARS-CoV-2 permite visualizar la posibilidad de establecer tratamientos farmacologicos o desarrollo de vacunas para controlar y disminuir los efectos patogenicos de la enfermedad In late December 2019, a new coronavirus (SARS-CoV-2) was identified as a causative agent of a new respiratory disease called COVID-19 by WHO Its symptoms include fever, dry cough, and shortness of breath Generally, these symptoms are mild, although, can be fatal in older adults and patients with comorbidities A bibliographic search was carried out in Pubmed and Clinical Key 22 articles were selected according to inclusion criteria SARS-CoV-2 belongs to the genus of Betacoronaviruses and has genomic similarities to SARS-CoV and MERS-CoV SARS-CoV-2 virion is made up of a nucleocapsid and external envelope composed of main structural and accesory proteins Its genetic is a positive sense single stranded RNA in which important proteins are encoded for their transcription and replication The mechanism of SARS-CoV-2 infection begins with the binding of the virion to (ACE2) receptor of the host cell and subsequent entry by endocytosis This RNA genome is released into cytoplasm and the necessary proteins for the production of structural proteins and the replication of genetic material are transcribed and translated Then, the replicated RNA associates with the nucleocapsid and assembles together with the structural proteins to form the viral particles that will be released from the infected cell The immune system faces viral infection through the recognition of molecular patterns associated with pathogens (PAMPs) by innate immunity and the action of T cells and B cells by humoral immunity Knowledge of the genetic and molecular basis of SARS-CoV-2 allows us to visualize the possibility of establishing pharmacological or vaccine treatments to control and reduce the pathogenic effects of the disease

The purpose of this study was aimed to isolate a Salmonella Typhimurium-specific phage (KFS-ST) from washing water in a poultry processing facility and to investigate the feasibility of the KFS-ST as a novel bio-receptor for the magnetoelastic (ME) biosensor method. KFS-ST against S. Typhimurium was isolated, propagated, and purified using a CsCl-gradient ultracentrifugation. Morphological characteristics of KFS-ST were analyzed using transmission electron microscopy (TEM). Its specificity and efficiency of plating analysis were conducted against 39 foodborne pathogens. The temperature and pH stabilities of KFS-ST were investigated by the exposure of the phage to various temperatures (−70°C–70°C) and pHs (1–12) for 1 h. A one-step growth curve analysis was performed to determine the eclipse time, latent time and burst size of phage. The storage stability of KFS-ST was studied by exposing KFS-ST to various storage temperatures (−70°C, −20°C, 4°C, and 22°C) for 12 weeks. KFS-ST was isolated and purified with a high concentration of (11.47 ± 0.25) Log PFU/mL. It had an icosahedral head (56.91 ± 2.90 nm) and a non-contractile tail (225.49 ± 2.67 nm), which was classified into the family of Siphoviridae in the order of Caudovirales. KFS-ST exhibited an excellent specificity against only S. Typhimurium and S. Enteritidis, which are considered two of the most problematic Salmonella strains in the meat and poultry. However, KFS-ST did not exhibit any specificity against six other Salmonella and 27 non-Salmonella strains. KFS-ST was stable at temperature of 4°C to 50°C and at pH of 4 to 12. The eclipse time, latent time, and burst size of KFS-ST were determined to be 10 min, 25 min and 26 PFU/ infected cell, respectively. KFS-ST was relatively stable during the 12-week storage period at all tested temperatures. Therefore, this study demonstrated the feasibility of KFS-ST as a novel bio-receptor for the detection of S. Typhimurium and S. Enteritidis in meat and poultry products using the ME biosensor method.

The outbreaks of viruses with wide spread and mortality in the world population have motivated the research for new therapeutic approaches. There are several viruses that cause a biochemical imbalance in the infected cell resulting in oxidative stress. These effects may be associated with the development of pathologies and worsening of symptoms. Therefore, this review is aimed at discussing natural compounds with both antioxidant and antiviral activities, specifically against coronavirus infection, in an attempt to contribute to global researches for discovering effective therapeutic agents in the treatment of coronavirus infection and its severe clinical complications. The contribution of the possible action of these compounds on metabolic modulation associated with antiviral properties, in addition to other mechanisms of action, is presented.

Oncolytic viruses are designed to replicate in and kill cancer cells, and have shown tremendous promise in preclinical and clinical studies. Indeed, several oncolytic viruses are available to patients in a number of different countries around the world. However, most oncolytic viruses show a poor ability to spread throughout the tumor mass, frequently leading to only a partial response and regrowth of the tumor. One approach to improve spread of the viral effect throughout the tumor mass is to arm the oncolytic virus with a fusogenic protein. In this manner, a single infected cell can fuse with many adjacent uninfected cells, essentially amplifying the anti-tumor effects. In this review, we discuss the development and use of fusogenic proteins to enhance the efficacy of human adenovirus-based vectors for cancer therapy.

This paper proposes and analyzes a CTL-mediated HIV infection model. The model describes the interaction between healthy CD4+T cells, silent infected cells, active infected cells, free HIV particles, and cytotoxic T lymphocytes (CTLs). The healthy CD4+T cells can be infected when contacted by one of the following: (i) free HIV particles, (ii) silent infected cells, and (iii) active infected cells. The incidence rates of the healthy CD4+T cells with free HIV particles, silent infected cells, and active infected cells are given by general functions. Moreover, the production/proliferation and removal/death rates of all compartments are represented by general functions. The model is an improvement of the existing HIV infection models which have neglected the incidence between the silent infected cells and healthy CD4+T cells. We first show that the model is well posed. The proposed model has three equilibria and their existence is governed by derived two threshold parameters: the basic HIV reproduction number $\Re _{0}$ ℜ 0 and the HIV-specific CTL-mediated immunity reproduction number $\Re _{1}$ ℜ 1 . Under a set of conditions on the general functions and the parameters $\Re _{0}$ ℜ 0 and $\Re _{1}$ ℜ 1 , we have proven the global asymptotic stability of all equilibria by using Lyapunov method. We have illustrated the theoretical results via numerical simulations. We have studied the effect of cell-to-cell (CTC) transmission on the dynamical behavior of the system. We have shown that inclusion of CTC transmission decreases the concentration of healthy CD4+T cells and increases the concentrations of infected cells and free HIV particles.

Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) for its assembly and release. Current HBV treatments are only marginally effective against HDV because they fail to inhibit HBsAg production/secretion. However, monotherapy with the nucleic acid polymer REP 2139-Ca is accompanied by rapid declines in both HBsAg and HDV RNA. We used mathematical modeling to estimate HDV-HBsAg-host parameters and to elucidate the mode of action and efficacy of REP 2139-Ca against HDV in 12 treatment-naive HBV/HDV co-infected patients. The model accurately reproduced the observed decline of HBsAg and HDV, which was simultaneous. Median serum HBsAg half-life (t1/2) was estimated as 1.3 [0.9–1.8] days corresponding to a pretreatment production and clearance of ~108 [107.7–108.3] IU/day. The HDV-infected cell loss was estimated to be 0.052 [0.035–0.074] days−1 corresponding to an infected cell t1/2 = 13.3 days. The efficacy of blocking HBsAg and HDV production were 98.2 [94.5–99.9]% and 99.7 [96.0–99.8]%, respectively. In conclusion, both HBsAg production and HDV replication are effectively inhibited by REP 2139-Ca. Modeling HBsAg kinetics during REP 2139-Ca monotherapy indicates a short HBsAg half-life (1.3 days) suggesting a rapid turnover of HBsAg in HBV/HDV co-infection.

Adherent-invasive Escherichia coli (AIEC) strains have been extensively related to Crohn's disease (CD) etiopathogenesis. Higher AIEC prevalence in CD patients versus controls has been reported, and its mechanisms of pathogenicity have been linked to CD physiopathology. In CD, the therapeutic armamentarium remains limited and non-curative; hence, the necessity to better understand AIEC as a putative instigator or propagator of the disease is certain. Nonetheless, AIEC identification is currently challenging because it relies on phenotypic assays based on infected cell cultures which are highly time-consuming, laborious and non-standardizable. To address this issue, AIEC molecular mechanisms and virulence genes have been studied; however, a specific and widely distributed genetic AIEC marker is still missing. The finding of molecular tools to easily identify AIEC could be useful in the identification of AIEC carriers who could profit from personalized treatment. Also, it would significantly promote AIEC epidemiological studies. Here, we reviewed the existing data regarding AIEC genetics and presented those molecular markers that could assist with AIEC identification. Finally, we highlighted the problems behind the discovery of exclusive AIEC biomarkers and proposed strategies to facilitate the search of AIEC signature sequences.

Significance Quantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is important for understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here, we developed within-host models of SARS-CoV-2 infection, and by fitting them to clinical data, we estimated key within-host viral dynamic parameters. We also developed a mechanistic model for viral transmission and show that the logarithm of the viral load in the upper respiratory tract serves as an appropriate surrogate for a person’s infectiousness. Using data on how viral load changes during infection, we further evaluated the effectiveness of PCR and antigen-based testing strategies for averting transmission and identifying infected individuals., The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person’s infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop viral dynamic models of SARS-CoV-2 infection and fit them to data to estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking viral load (VL) to infectiousness and show a person’s infectiousness increases sublinearly with VL and that the logarithm of the VL in the upper respiratory tract is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and RT-PCR tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies.

The integration of a viral genome into the host genome has a major impact on the trajectory of the infected cell. Integration location and variation within the associated viral genome can influence both clonal expansion and persistence of infected cells. Methods based on short-read sequencing can identify viral insertion sites, but the sequence of the viral genomes within remains unobserved. We develop PCIP-seq, a method that leverages long reads to identify insertion sites and sequence their associated viral genome. We apply the technique to exogenous retroviruses HTLV-1, BLV, and HIV-1, endogenous retroviruses, and human papillomavirus., SCOPUS: ar.j, info:eu-repo/semantics/published

Dengue infection affects more than half of the world’s population, with 1 billion symptomatic 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 mathematical 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.

In this paper, we study possibilities of eradication of populations at an early stage of a patient’s infection in the framework of the seven-order Stengel model with 11 model parameters and four treatment parameters describing the interactions of wild-type and mutant HIV particles with various immune cells. We compute ultimate upper bounds for all model variables that define a polytope containing the attracting set. The theoretical possibility of eradicating HIV-infected populations has been investigated in the case of a therapy aimed only at eliminating wild-type HIV particles. Eradication conditions are expressed via algebraic inequalities imposed on parameters. Under these conditions, the concentrations of wild-type HIV particles, mutant HIV particles, and infected cells asymptotically tend to zero with increasing time. Our study covers the scope of acceptable therapies with constant concentrations and values of model parameters where eradication of infected particles/cells populations is observed. Sets of parameter values for which Stengel performed his research do not satisfy our local asymptotic stability conditions. Therefore, our exploration develops the Stengel results where he investigated using the optimal control theory and numerical dynamics of his model and came to a negative health prognosis for a patient. The biological interpretation of these results is that after a sufficiently long time, the concentrations of wild-type and mutant HIV particles, as well as infected cells will be maintained at a sufficiently low level, which means that the viral load and the concentration of infected cells will be minimized. Thus, our study theoretically confirms the possibility of efficient treatment beginning at the earliest stage of infection. Our approach is based on a combination of the localization method of compact invariant sets and the LaSalle theorem.