Background: HCMV causes severe clinical complications in transplant recipients and may lead to graft rejection. Successful renal transplantation heavily relies on the early prevention and diagnosis of CMV infections, followed by prompt prophylactic treatment before transplantation. Despite the majority of renal rejection cases with acute HCMV infections being asymptomatic and occurring one to two years later, the objective of this research was to comprehend the effect of late HCMV infection on renal rejection by examining specific clinical parameters in the Eastern Indian cohort. Method: In this study, 240 patients were studied for five years following transplantation, and their data were collected from the local metropolitan hospital in Eastern India. Both HCMV-positive and -negative post-transplant patients were investigated using the clinical parameters and viral loads for latent infection. Results: Within the studied population, 79 post-transplant patients were found to be HCMV positive. Among them, 13 (16.45%) patients suffered from renal rejection within less than 2 yrs. of transplantation (early rejection) and 22 (27.84%) patients suffered from renal rejection after 2 yrs. from the operation date (late rejection). Assessment of clinical parameters with respect to HCMV infection revealed that in early rejection cases, fever (p-0.035) and urinary tract infection (p-0.017) were prominent, but in late rejection, hematuria (p-0.032), diabetes (p-0.005), and creatinine level changes (p < 0.001) were significant along with urinary tract infection (p-0.047). Conclusions: This study provides valuable insights into monitoring latent CMV infections and highlights the understanding of reducing renal rejection rates and the need for further research in this field.

Rhodococcus equi has recently been identified in various animals, including ruminants. Several studies have highlighted the emergence of pVAPN-harboring strains, isolated from multiple abscesses, in the liver and lungs of ruminants. Epidemiological evidence strongly suggests that pVAPN-harboring strains are pathogenic in ruminants. This study aims to replicate the disease in goats through experimental infection. Intravenous administration of the pVAPN-harboring strain (Yokkaichi), pVAPA-harboring strain (ATCC33701), and pVAPN-cured strain (Yokkaichi_P-), each at 1.0 × 107 CFU/head, was conducted in 24-month-old goats (n = 1 per group). During the observation period, goats treated with Yokkaichi or ATCC33701 exhibited transient increases in body temperature and white blood cell count, alongside a decrease in body weight from the administration day. Conversely, goats treated with Yokkaichi_P- displayed no significant changes in these values. The Yokkaichi-treated goat demonstrated a >10-fold increase in anti-VapN antibody titers from 11 to 14 days postadministration, whereas the other two goats exhibited no variation in anti-VapA and VapN antibody titers. Pathological autopsy analysis of organs harvested 28 days postadministration revealed no characteristic lesions on gross examination. However, the inoculated strain (vapN-positive R. equi) was exclusively recovered from the tracheobronchial lymph node in the Yokkaichi-treated goat. Immunohistochemistry detected a VapN-positive reaction in the tracheobronchial lymph node, confirming latent infection despite the absence of dramatic suppurative lesions seen in ruminants. Overall, this study highlights the latent infection in lymph nodes induced by the pVAPN-harboring strain, despite the absence of overt pathological manifestations.

Chronic Toxoplasma gondii infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by T. gondii leading to effective CD8+ T cell-mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite-specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell-dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during T. gondii latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell-mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.

Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL).
Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and >60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling.
The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3-4 viruses (vs. 0-2) was associated with a shorter LTL.
Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain a latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV)-latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells and SeMNPV or Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells, and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in the G2/M phase or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that, compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, budded virus (BV) production and occlusion body (OB)-containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post-infection (p < 0.05). Finally, the arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB-containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression and regulation.

Most people infected with Mycobacterium tuberculosis (Mtb) are believed to be in a state of latent tuberculosis (TB) infection (LTBI). Although LTBI is asymptomatic and not infectious, there is a risk of developing active disease even decades after infection. Here, to characterize mutations acquired during LTBI, we collected and analyzed Mtb genomes from seven Japanese patient pairs, each pair consisting of two active TB patients whose starting dates of developing active disease were >3 years apart; one had a high suspicion of LTBI before developing active disease, whereas the other did not. Thereafter, we compared these genomes with those of longitudinal sample pairs within a host of chronic active TB infections combined with public data. The bacterial populations in patients with LTBI were genetically more homogeneous and accumulated single nucleotide polymorphisms (SNPs) slower than those from active disease. Moreover, the lower proportion of nonsynonymous SNPs indicated weaker selective pressures during LTBI than active disease. Finally, the different mutation spectrums indicated different mutators between LTBI and active disease. These results suggest that the likelihood of the acquisition of mutations responsible for antibiotic resistance and increased virulence was lower in the Mtb population from LTBI than active disease.IMPORTANCEControlling latent tuberculosis (TB) infection (LTBI) activation is an effective strategy for TB elimination, where understanding Mycobacterium tuberculosis (Mtb) dynamics within the host plays an important role. Previous studies on chronic active disease reported that Mtb accumulated genomic mutations within the host, possibly resulting in acquired drug resistance and increased virulence. However, several reports suggest that fewer mutations accumulate during LTBI than during the active disease, but the associated risk is largely unknown. Here, we analyzed the genomic dynamics of Mtb within the host during LTBI. Our results statistically suggest that Mtb accumulates mutations during LTBI, but most mutations are under low selective pressures, which induce mutations responsible for drug resistance and virulence. Thus, we propose that LTBI acts as a source for new TB disease rather than as a period for in-host genome evolution.

We retrospectively analyzed of 211 frozen cerebrospinal fluid samples from immunocompetent persons in the Czech Republic and detected 6 Encephalitozoon cuniculi-positive samples. Microsporidiosis is generally underestimated and patients are not usually tested for microsporidia, but latent infection in immunodeficient and immunocompetent patients can cause serious complications if not detected and treated.

BACKGROUND: Accumulating evidence suggests that latent infection with Toxoplasma gondii (T. gondii) is associated with a variety of neuropsychiatric and behavioral conditions. This research aims to explore the potential correlation between T. gondii antibody positivity and neuropsychiatric disorders through a comprehensive prospective cohort study.
METHODS: The cohort study utilized the UK Biobank database to recruit 8814 individuals with no prior diagnosis of neuropsychiatric disorders. Cox proportional hazards models were employed to investigate the associations between T. gondii P22 antibody seropositivity (P22+) and the development of various types of neuropsychiatric disorders.
RESULTS: Of the population, 14.65 % tested positive for T. gondii P22 antibody. The presence of T. gondii P22 antibody showed a slight inverse association with epilepsy (HR: 0.28; 95 % CI: 0.10-0.77), while it was positively associated with an increased risk of developing anxiety disorders (HR: 1.38; 95 % CI: 1.04-1.83).
CONCLUSIONS: The study sample consisted mostly of white British individuals aged 40 to 69 years old. Although we adjusted for potential confounders, there may be other unmeasured and residual confounding factors that could have influenced our reported associations.
CONCLUSIONS: The findings suggested an increased risk of anxiety and potential evidence of epilepsy associated with T. gondii P22+. However, our analysis did not reveal an increased risk of several other neuropsychiatric conditions including Alzheimer\'s disease, dementia, substance abuse disorders, depression, and neurodegenerative disorders, associated with P22 antibody seropositivity.

暂无摘要。

暂无摘要。