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Taking into account the effects of the immune response and delay, and complexity on HIV-1 transmission, a multiscale AIDS/HIV-1 model is formulated in this paper. The multiscale model is described by a within-host fast time model with intracellular delay and immune delay, and a between-host slow time model with latency delay. The dynamics of the fast time model is analyzed, and includes the stability of equilibria and properties of Hopf bifurcation. Further, for the coupled slow time model without an immune response, the basic reproduction number R 0 h is defined, which determines whether the model may have zero, one, or two positive equilibria under different conditions. This implies that the slow time model demonstrates more complex dynamic behaviors, including saddle-node bifurcation, backward bifurcation, and Hopf bifurcation. For the other case, that is, the coupled slow time model with an immune response, the threshold dynamics, based on the basic reproduction number R ˜ 0 h , is rigorously investigated. More specifically, if R ˜ 0 h < 1 , the disease-free equilibrium is globally asymptotically stable; if R ˜ 0 h > 1 , the model exhibits a unique endemic equilibrium that is globally asymptotically stable. With regard to the coupled slow time model with an immune response and stable periodic solution, the basic reproduction number R 0 is derived, which serves as a threshold value determining whether the disease will die out or lead to periodic oscillations in its prevalence. The research results suggest that the disease is more easily controlled when hosts have an extensive immune response and the time required for new immune particles to emerge in response to antigenic stimulation is within a certain range. Finally, numerical simulations are presented to validate the main results and provide some recommendations for controlling the spread of HIV-1. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant tumours and the third most common cause of cancer deaths worldwide, with high morbidity and mortality. Circadian clocks are widespread in humans and temporally regulate physiologic functions to maintain homeostasis. Recent studies showed that circadian components were strong regulators of the tumour immune microenvironment (TIME) and the immunogenicity of CRC cells. Therefore, insight into immunotherapy from the perspective of circadian clocks can be promising. Although immunotherapy, especially immune checkpoint inhibitor (ICI) treatment, has been a milestone in cancer treatment, greater accuracy is still needed for selecting patients who will respond positively to immunotherapy with minimal side effects. In addition, there were few reviews focusing on the role of the circadian components in the TIME and the immunogenicity of CRC cells. Therefore, this review highlights the crosstalk between the TIME in CRC and the immunogenicity of CRC cells based on the circadian clocks. With the goal to achieve the possibility that patients with CRC can benefit most from the ICI treatment, we provide potential evidence and a novel idea for building a predictive framework combined with circadian factors, searching for enhancers of ICIs targeting circadian components and clinically implementing the timing of ICI treatment for patients with CRC. [ABSTRACT FROM AUTHOR]

Background: The immunogenicity and safety of COVID-19 vaccines among people living with human immunodeficiency virus (PLWH) are unclear. We aimed to evaluate the immunogenicity and safety of COVID-19 vaccines among PLWH. Methods: We systematically searched PubMed, EMBASE, and Web of Science from 1 January 2020 to 28 April 2022 and included observational studies, randomized clinical trials, and non-randomized clinical trials reporting extractable data about the immunogenicity and safety of COVID-19 vaccines among PLWH. Results: A total of 34 eligible studies covering 4517 PLWH were included. The pooled seroconversion rates among PLWH after the first and second doses were 67.51% (95% confident interval (CI) 49.09–85.93%) and 96.65% (95%CI 95.56–97.75%), respectively. The seroconversion was similar between PLWH and healthy controls after the first (risk ratio (RR) = 0.89, 95%CI 0.76–1.04) and the second (RR = 0.97, 95%CI 0.93–1.00) dose. Moreover, the geometric mean titer (GMT) showed no significant difference between PLWH and healthy controls after the first dose (standardized mean difference (SMD) = 0.30, 95%CI -1.11, 1.70) and the second dose (SMD = -0.06, 95%CI -0.18, 0.05). Additionally, the pooled incidence rates of total adverse events among PLWH after the first and the second dose were 46.55% (95%CI 28.29–64.82%) and 30.96% (95%CI 13.23–48.70%), respectively. There was no significant difference in risks of total adverse events between PLWH and healthy controls after the first (RR = 0.86, 95%CI 0.67–1.10) and the second (RR = 0.88, 95%CI 0.68–1.14) dose. Conclusions: The available evidence suggested that the immunogenicity and safety of COVID-19 vaccines among PLWH were acceptable. There was no significant difference in the seroconversion rates and incidence rates of adverse events of COVID-19 vaccines between PLWH and healthy controls. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year. The quality of immune response to SARS-CoV-2 is thought to wane over time, but it is unclear how long it can persist. Here the authors show persistent immune responses in a large number of patients over the course of a 1-year follow-up from the time of recovery from COVID-19. [ABSTRACT FROM AUTHOR]

Grass carp (Ctenopharyngodon idellus) is an important aquaculture species in China that is affected by serious diseases, especially hemorrhagic disease caused by grass carp reovirus (GCRV). Grass carp have previously shown age-dependent susceptibility to GCRV, however, the mechanism by which this occurs remains poorly understood. Therefore, we performed transcriptome and metabolome sequencing on five-month-old (FMO) and three-year-old (TYO) grass carp to identify the potential mechanism. Viral challenge experiments showed that FMO fish were susceptible, whereas TYO fish were resistant to GCRV. RNA-seq showed that the genes involved in immune response, antigen presentation, and phagocytosis were significantly upregulated in TYO fish before the GCRV infection and at the early stage of infection. Metabolome sequencing showed that most metabolites were upregulated in TYO fish and downregulated in FMO fish after virus infection. Intragroup analysis showed that arachidonic acid metabolism was the most significantly upregulated pathway in TYO fish, whereas choline metabolism in cancer and glycerophospholispid metabolism were significantly downregulated in FMO fish after virus infection. Intergroup comparison revealed that metabolites from carbohydrate, amino acid, glycerophospholipid, and nucleotide metabolism were upregulated in TYO fish when compared with FMO fish. Moreover, the significantly differentially expressed metabolites showed antiviral effects both in vivo and in vitro. Based on these results, we concluded that the immune system and host biosynthesis and metabolism, can explain the age-dependent viral susceptibility in grass carp. [ABSTRACT FROM AUTHOR]

Cathepsin B (CatB) is a cysteine proteolytic enzyme widely expressed in various cells and mainly located in the lysosomes. It contributes to the pathogenesis and development of many diseases. However, the role of CatB in viral myocarditis (VMC) has never been elucidated. Here we generated the VMC model by intraperitoneal injection of coxsackievirus B3 (CVB3) into mice. At day 7 and day 28, we found CatB was significantly activated in hearts from VMC mice. Compared with the wild-type mice receiving equal amount of CVB3, genetic ablation of CatB (Ctsb-/-) significantly improved survival, reduced inflammatory cell infiltration, decreased serum level of cardiac troponin I, and ameliorated cardiac dysfunction, without altering virus titers in hearts. Conversely, genetic deletion of cystatin C (Cstc-/-), which markedly enhanced CatB levels in hearts, distinctly increased the severity of VMC. Furthermore, compared with the control, we found the inflammasome was activated in the hearts of wild-type mice with VMC, which was attenuated in the hearts of Ctsb-/- mice but was further enhanced in Cstc-/- mice. Consistently, the inflammasome-initiated pyroptosis was reduced in Ctsb-/- mice hearts and further increased in Cstc-/- mice. These results suggest that CatB aggravates CVB3-induced VMC probably through activating the inflammasome and promoting pyroptosis. This finding might provide a novel strategy for VMC treatment. [ABSTRACT FROM AUTHOR]

Highlights: [•] Grass carp TRIF exhibits sequence divergence from its orthologs. [•] CiTRIF might activate IFN in distinct manner from that in mammals. [•] CiTRIF plays a critical role in RLR pathway in antiviral immune response. [•] CiTRIF inhibits GCRV replication in CIK cells. [ABSTRACT FROM AUTHOR]