Cells In Infection Research Articles

Pathology of Red Blood Cells in Patients with SARS-CoV-2

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with various hematological disorders. Understanding the pathology of erythrocytes (red blood cells) in coronavirus infection may provide insights into disease severity and progression. Objective: To review and analyze the general pathology of erythrocytes in patients infected with SARS-CoV-2, focusing on clinical and laboratory findings across different severity groups. Methods: Patients were classified into four groups based on clinical criteria: Group 1: Regular group (fever, respiratory symptoms, and radiographic evidence of pneumonia). Group 2: Severe group (shortness of breath >30 breaths/min, peripheral blood oxygen saturation <92% at rest, extensive pneumonia, respiratory failure requiring mechanical ventilation, and/or organ failure necessitating intensive care). Group 3: Low saturation group (peripheral blood oxygen saturation <85% at rest). Group 4: Erythroblastosis group (erythroblast count >0.5% among total nucleated blood cells). Clinical laboratory investigations included major routine studies and scanning microspectrophotometry to measure hemoglobin (Hb) spectra in unstained erythrocytes. Results: Erythroblasts were detected in approximately 30% of SARS-CoV-2 patients, predominantly in the severe group. Serum ferritin, C-reactive protein (CRP), and anisocytosis were strongly correlated with disease severity. Microspectrophotometric studies revealed significant changes in hemoglobin adsorption spectra, with an increase in Hb absorbance at 420 nm in severe cases compared to normal controls. Conclusions: Elevated serum ferritin, CRP levels, anisocytosis, and altered hemoglobin absorption at 420 nm wavelength are associated with adverse outcomes in SARS-CoV-2 infection. These findings highlight the potential utility of hematological parameters as markers for disease severity and prognosis in viral infections.

Recent Advances in Our Understanding of Human Inflammatory Dendritic Cells in Human Immunodeficiency Virus Infection

Anogenital inflammation is a critical risk factor for HIV acquisition. The primary preventative HIV intervention, pre-exposure prophylaxis (PrEP), is ineffective in blocking transmission in anogenital inflammation. Pre-existing sexually transmitted diseases (STIs) and anogenital microbiota dysbiosis are the leading causes of inflammation, where inflammation is extensive and often asymptomatic and undiagnosed. Dendritic cells (DCs), as potent antigen-presenting cells, are among the first to capture HIV upon its entry into the mucosa, and they subsequently transport the virus to CD4 T cells, the primary HIV target cells. This increased HIV susceptibility in inflamed tissue likely stems from a disrupted epithelial barrier integrity, phenotypic changes in resident DCs and an influx of inflammatory HIV target cells, including DCs and CD4 T cells. Gaining insight into how HIV interacts with specific inflammatory DC subsets could inform the development of new therapeutic strategies to block HIV transmission. However, little is known about the early stages of HIV capture and transmission in inflammatory environments. Here, we review the currently characterised inflammatory-tissue DCs and their interactions with HIV.

Self-amplifying RNA virus vectors for drug delivery.

Viral vectors have proven useful for delivering genetic information, such as drugs and vaccines, for therapeutic and prophylactic interventions. Self-amplifying RNA viruses possess the special feature of high-level RNA amplification in the host cell cytoplasm providing high antigen production against infectious pathogens and various types of cancers, and expression of anti-tumor genes, toxic genes, and immunostimulatory genes. Self-amplifying RNA viral vectors have been evaluated in animal models and clinical trials for immune responses and protection against challenges with pathogenic infectious agents and tumor cells. Likewise, immune responses, tumor regression, and tumor eradication have been monitored in preclinical and clinical settings. The literature search used in the review is based on PubMed and clinical trial/biotechnology company websites up until September 2024. Self-amplifying RNA viruses have elicited strong immune responses and vaccine efficacy in animal models and humans leading to the approval of the vesicular stomatitis virus-based vaccine against Ebola virus disease in both the US and Europe. Moreover, therapeutic and prophylactic efficacy has been demonstrated in animal tumor models and cancer patients. Self-amplifying RNA viruses have also been evaluated in mouse models for neurological disorders.

Role of follicular homing natural killer cells in HIV infection.

Natural killer (NK) cells are integral components of the innate immune system, serving a vital function in eliminating virally infected cells. This review highlights the significance of CXCR5+ NK cells in the context of chronic HIV/SIV infection and viral control. Controlled HIV/SHIV infection results in a substantial increase in the population of CXCR5+ NK cells within the B-cell follicles of secondary lymphoid organs (SLOs). These CXCR5+ NK cells display enhanced functional characteristics, including elevated expression of activation markers and increased cytokine production, which are essential for effective viral control. These follicular NK cells are shown to be enriched in IL-15 signaling, and CXCR5 NK cells are negatively associated with viral burden during chronic HIV and SHIV infection. The distinct phenotypic and functional attributes of CXCR5+ NK cells, particularly in the lymphoid tissues of individuals living with HIV, emphasize their critical contribution to the anti-HIV-1 immune response. A comprehensive understanding of the mechanisms and roles of CXCR5+ NK cells may present novel therapeutic strategies aimed at enhancing NK-mediated viral control.

Engineered Phage Enables Efficient Control of Gene Expression upon Infection of the Host Cell.

Recently, we developed a spatial phage-assisted continuous evolution (SPACE) system. This system utilizes chemotaxis coupled with the growth of motile bacteria during their spatial range expansion in soft agar to provide fresh host cells for iterative phage infection and selection pressure for preserving evolved genes of interest carried by phage mutants. Controllable mutagenesis activated only in a subpopulation of the migrating cells is essential in this system to efficiently generate mutated progeny phages from which desired individuals are selected during the directed evolution process. But, the widely adopted small molecule-dependent inducible system could hardly fulfill this purpose because it always affects all cells homogeneously. In this study, we developed a phage infection-induced gene expression system using modified Escherichia coli (E. coli) phage shock protein operon or sigma factors from Bacillus subtilis. Results showed that this system enabled efficient control of gene expression upon phage infection with dynamic output ranges from small to large using combinations of different engineered phages and corresponding promoters. This system was incorporated into SPACE to function as a phage infection-induced mutagenesis module and successfully facilitated the evolution of T7 RNA polymerase, which generated diverse mutants with altered promoter recognition specificity. We expect that phage infection-induced gene expression system could be further extended to more applications involving partial induction in a portion of a population and targeted induction in specific strains among a mixed bacterial community, which provides an important complement to small molecule-dependent inducible systems.

Loss of mucin 2 and MHC II molecules causes rare resistance to murine RV infection.

Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, based on lack of shedding virus, despite the highly infectious nature of RV. This response was directly proportional to the extent of secretory cell deletion, with infection predominantly occurring in areas containing intact secretory cells. RV infection of Muc2 knockout mice recapitulated the secretory cell deletion phenotype, indicating that goblet cell loss is responsible for attenuated infection. Transcriptome analysis of Atoh1cKO intestine via single-cell RNA sequencing revealed downregulation of MHC II molecules specifically in tip enterocytes, and MHC II-/- mice were likewise resistant to RV infection. These data suggest a previously unknown role for both MUC2 and MHC II expression in susceptibility to RV infection.IMPORTANCERotavirus (RV) is a highly contagious pathogen that primarily infects mature intestinal enterocytes. Murine rotavirus readily infects infant and adult mice, enabling evaluation of RV infection and immunity. We report that mice lacking secretory cells are one of the few genetically modified mouse lines not susceptible to murine rotavirus. Further investigation revealed loss of mucin 2 (MUC2) expression or major histocompatibility complex II (MCH II) expression recapitulated this rare resistance to rotavirus infection, suggesting a previously unrecognized link between secretory cell products and major histocompatibility complex II expression. Furthermore, these mouse models provide a platform to investigate rotavirus pathogenesis.

B cells in chronic hepatitis: advances and mechanistic

The article reviews the role and functional diversity of B cells in chronic hepatitis B (CHB). B cells play a crucial role in humoral immunity, participating in the clearance of hepatitis B virus (HBV) through antibody production, antigen presentation, and immune regulation. In HBV infection, B cells exhibit antigenic heterogeneity, with immune responses to different HBV antigens varying. Recent findings reveal that in CHB patients, hepatitis B surface antibody-specific B cells are abnormally differentiated, while hepatitis B core antibody-specific B cells maintain relatively intact functions. Moreover, the deficiency in non-antibody-producing functions of B cells may lead to persistent HBV infection. The article provides important insights into the role of B cells in HBV infection and offers a scientific basis for the development of new therapeutic strategies.

Sensory innervation in the prostate and a role for calcitonin gene-related peptide in prostatic epithelial proliferation.

The prostate is densely innervated like many visceral organs and glands. However, studies to date have focused on sympathetic and parasympathetic nerves and little attention has been given to the presence or function of sensory nerves in the prostate. Recent studies have highlighted a role for sensory nerves beyond perception of noxious stimuli, as anterograde release of neuropeptides from sensory nerves can affect vascular tone and local immune responses. To identify the degree of sensory innervation in the prostate, we utilized state-of-the-art tissue clearing and microscopy to visualize sensory innervation in the different lobes of the mouse prostate. To determine whether sensory nerves have a role in regulating proliferation within the prostate, we used an intersectional genetic and toxin approach to ablate peptidergic sensory nerves systemically. We found that sensory neurons are abundant in the prostate both in nerve bundles along the vasculature and as independent nerve fibers wrapped around prostatic acini in a net-like fashion. In addition to the dense innervation of the prostate, we found that Calca haploinsufficiency, the genotype control for our intersectional ablation model, results in a diminished level of Ki67 staining in the stromal compartment of the dorsal lobe and a diminishing Ki67 trend in other lobes. These findings suggest that sensory neurons might have developmental or homeostatic effects within the prostate. Further studies are warranted to assess the role of sensory neurons and the sensory neuropeptides on prostatic development and on proliferation in the presence of pro-inflammatory stimuli such as bacterial infection or tumor cells.

Nutrient-driven histone code determines exhausted CD8+ T cell fates.

Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from acetate to citrate metabolism by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity. This metabolic switch increased citrate-dependent histone acetylation, mediated by histone acetyltransferase KAT2A-ACLY interactions, at TEX signature-genes while reducing acetate-dependent histone acetylation, dependent on p300-ACSS2 complexes, at effector and memory T cell genes. Nuclear ACSS2 overexpression or ACLY inhibition prevented TEX differentiation and enhanced tumor-specific T cell responses. These findings unveiled a nutrient-instructed histone code governing CD8+ T cell differentiation, with implications for metabolic- and epigenetic-based T cell therapies.

Peripheral B Lymphocyte Serves as a Reservoir for the Persistently Covert Infection of Mandarin Fish Siniperca chuatsi Ranavirus.

Mandarin fish ranavirus (MRV) is a distinctive member among the genus Ranavirus of the family Iridoviridae. The persistently covert infection of MRV was previously observed in a natural outbreak of MRV, but the underlying mechanism remains unclear. Here, we show that mandarin fish peripheral B lymphocytes are implemented as viral reservoirs to maintain the persistent infection. When mandarin fish were infected with a sublethal dosage of MRV under a nonpermissive temperature (19 °C) and a permissive temperature (26 °C), all of the fish in the 19 °C group survived and entered the persistent phase of infection, characterized by a very low viral load in white blood cells, whereas some of the fish died of MRV infection in the 26 °C group, and the survival fish then initiated a persistent infection status. Raising the temperature, vaccination and dexamethasone treatment can reactivate the quiescent MRV to replicate and result in partial mortality. The viral reservoir investigation showed that IgM+-labeled B lymphocytes, but not CD3Δ+-labeled T lymphocytes and MRC-1+-labeled macrophages, are target cells for the persistent infection of MRV. Moreover, the reactivation of the quiescent MRV was confirmed through a non-TLR5 signal pathway manner. Collectively, we demonstrate the presence of the B cell-dependent persistent infection of ranavirus, and provide a new clue for better understanding the complex infection mechanism of vertebrate iridovirus.

Annexin- and calcium-regulated priming of legume root cells for endosymbiotic infection

Legumes establish endosymbioses with arbuscular mycorrhizal (AM) fungi or rhizobia bacteria to improve mineral nutrition. Symbionts are hosted in privileged habitats, root cortex (for AM fungi) or nodules (for rhizobia) for efficient nutrient exchange. To reach these habitats, plants form cytoplasmic cell bridges, key to predicting and guiding fungal hyphae or rhizobia-filled infection thread (IT) root entry. However, the underlying mechanisms are poorly studied. Here we show that unique ultrastructural changes and calcium (Ca2+) spiking signatures, closely associated with Medicago truncatula Annexin 1 (MtAnn1) accumulation, accompany rhizobia-related bridge formation. Loss of MtAnn1 function in M. truncatula affects Ca2+ spike amplitude, cytoplasmic configuration and rhizobia infection efficiency, consistent with a role of MtAnn1 in regulating infection priming. MtAnn1, which evolved in species establishing intracellular symbioses, is also AM-symbiosis-induced and required for proper arbuscule formation. Together, we propose that MtAnn1 is part of an ancient Ca2+-regulatory module for transcellular endosymbiotic infection.

Relationship between the risk of intestinal mucosal Epstein-Barr virus and/or cytomegalovirus infection and peripheral blood NK cells numbers in patients with ulcerative colitis: a cross-sectional study in Chinese population.

This study aimed to analyze the relationship between the risk of common opportunistic pathogens Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in intestinal mucosal tissues of Ulcerative Colitis (UC) patients and the number of peripheral blood NK cells. UC patients admitted to a third-grade class-A hospital from January 2018 to December 2023 were selected as research population. Clinical data of the patients were collected from the electronic medical record system. Additionally, samples of intestinal mucosal tissues were obtained for real-time fluorescence quantitative PCR to detect and analyze the viral load of CMV and EBV. Blood samples were collected for lymphocyte subsets analysis. Multivariable logistic regression models analyses was used to determine the odds ratio (OR) and 95% confidence interval (95% CI) for the independent association between NK cells and EBV/CMV infections in UC. We further applied the restricted cubic spline analysis and smooth curve fitting to examine the non-linear relationship between them. 378 UC patients were enrolled. Of these patients, there were 194 patients (51.32%) with EBV /CMV infection. In multivariable logistic regression analyses NK cells was independently associated with EBV and/or CMV infection after adjusted potential confounders (OR 8.24, 95% CI 3.75-18.13, p < 0.001). A nonlinear relationship was found between NK cells and EBV/CMV infections, which had a threshold around 10.169. The effect sizes and CIs below and above the threshold were 0.535 (0.413-0.692), p < 0.001 and 1.034 (0.904-1.183), p > 0.05, respectively. There was a non-linear relationship between NK cells and EBV/CMV infections. The risk for EBV/CMV infections was not increased with increasing NK cells in individuals with NK cells ≥ 10.169%, whereas the risk for EBV and/or CMV infection was increased with an decreasing NK cells in those with NK cells < 10.169%. The risk of EBV/CMV infections increases when NK cells were below a certain level.

A new record of avian reovirus genogroup clusters isolated and molecularly characterized in chickens in Egypt

BackgroundThe global poultry industry has been experiencing increasing condemnation at slaughterhouses since 2011, due to the emergence of avian reovirus (ARV) variant strains. Recently seven ARV genogroup clusters were identified based on the σC sequence of the S1 segment that was used as a genetic marker to characterize and classify ARV.ResultsAmong ninety-seven suspected broilers, breeders, and commercial grandparent’s homogenates, ARV was PCR confirmed in thirty-five (36%). Samples were collected from different governorates in Egypt, including Giza–Ismailia–Sharqia–Menoufia, and Behira, between 2020 and 2023. A viral isolation trial was performed on weak positive samples, successfully isolating sixteen samples on the LMH cell line forming the characteristic giant cells of ARV infection. Partial sequencing and phylogenetic analysis of the σC gene of ten ARV PCR positive samples revealed the circulation of ARV genogroup clusters 1, 2, 4, and 5, eight samples being distinguished from commercially available vaccine strains with a low percentage of nucleotides and amino acid identities.ConclusionsThis research demonstrated that the ARV isolates were distinct compared to commercially available vaccine strains based on partial σC sequence. Detection, isolation, and classification of ARV as genogroups 1, 2, 4, and 5 are recorded. A vigilant surveillance to evaluate the ARV situation in Egypt is urgent. We recommend re-evaluating the ARV commercial vaccines by challenging them with circulating Egyptian field isolates, as well as their cross-protection. In addition, the development of autologous vaccines from both classical and variant strains to provide optimal protection.

Transcriptional profiling of zebrafish intestines identifies macrophages as host cells for human norovirus infection.

Human noroviruses (HuNoVs) are a major cause of diarrheal disease, yet critical aspects of their biology, including cellular tropism, remain unclear. Although research has traditionally focused on the intestinal epithelium, the hypothesis that HuNoV infects macrophages has been recurrently discussed and is investigated here using a zebrafish larval model. Through single-cell RNA sequencing of dissected zebrafish intestines, we unbiasedly identified macrophages as host cells for HuNoV replication, with all three open reading frames mapped to individual macrophages. Notably, HuNoV preferentially infects actively phagocytosing inflammatory macrophages. HuNoV capsid proteins and double-stranded RNA colocalized within intestinal macrophages of infected zebrafish larvae, and the negative-strand RNA intermediate was detected within FACS-sorted macrophages. Flow cytometry confirmed viral replication within these macrophages, constituting approximately 23% of HuNoV's host cells. Identifying macrophages as host cells prompts a reevaluation of their role in HuNoV pathogenesis, offering new directions for understanding and controlling this infection.

Infectious morbidity and white blood cell count associated with grade repetition and school absenteeism.

Infections can impair cognitive development, but their role on adverse childhood educational outcomes is unknown. We examined the associations of infectious morbidity and inflammatory biomarkers with grade repetition and school absenteeism. We followed 2762 Colombian children aged 5-12 years for a school year. We quantified inflammatory biomarkers at enrolment and prospectively recorded incidence of gastrointestinal and respiratory infections, doctor visits and absent days from school using pictorial diaries. We estimated adjusted relative risks (ARR) with 95% confidence intervals (CI) for grade repetition and absenteeism by infectious morbidity burden and inflammatory biomarker categories, and percentages of the associations mediated through absenteeism. Morbidity was associated with increased risk of grade repetition. ARR (95% CI) of grade repetition comparing high versus no incidence of gastrointestinal, respiratory and ear infections were, respectively, 2.17 (1.00, 4.72), 2.31 (1.28, 4.16) and 2.57 (1.13, 5.86). Infections also predicted school absenteeism, which mediated 35%, 31% and 38% of the corresponding morbidity-grade repetition associations. Elevated white blood cells (WBC), especially granulocytes, were related to increased grade repetition and school absenteeism risks. Childhood infections and elevated WBC are associated with grade repetition and school absenteeism. Absenteeism does not fully explain the morbidity-grade repetition associations.

EXTH-67. ONCOLYTIC ADENOVIRAL INFECTION OF CHORDOMA ACHIEVES TREATMENT EFFICACY THROUGH IMMUNOGENIC CELL DEATH AND TUMOR MICROENVIRONMENT ALTERATION

Abstract Chordomas are locally aggressive neoplasms of the axial skeleton with recurrence rates approaching 40%. Moreover, recurrent chordomas are nearly impossible to eradicate—highlighting an unmet clinical need. Immunotherapeutic approaches, such as immune checkpoint inhibition (ICI), has been a successful tool to modulate the tumor microenvironment (TME) towards a pro-inflammatory, antitumor state. There is emerging interest in exploring immunomodulatory agents for chordomas. Oncolytic viral (OV) therapy uses genetically modified viruses which selectively replicate in tumor cells, mediate tumor cell lysis, and initiate a pro-inflammatory response within the infected TME. These findings suggest that OV therapy may be a clinically relevant, novel immunotherapeutic approach for chordoma. Using the replicating oncolytic adenovirus Delta-24-RGD, we investigate the efficacy of chordoma treatment using in vitro approaches, ex vivo bone scaffolds, and in vivo murine models. Additionally, we explore the underlying mechanism of OV cytotoxicity, immunogenic cell death, Brachyury modulation, and reshaping of the TME towards a pro-inflammatory state. Across a panel of human chordoma cell lines, Delta-24-RGD achieved viral infectivity, oncolysis and immunogenic cell death. This treatment response was similarly demonstrated in chordoma cultured in bone scaffold models. Delta-24-RGD infection was associated with concomitant Brachyury downregulation within both infected and uninfected chordoma cells in vitro, suggesting a pleiotropic effect following oncolytic viral infection. In vivo models of CH22 chordoma treated with Delta-24-RGD demonstrated shrinkage in tumor volume and enhanced overall survival. Utilizing a human chordoma tissue microarray, the immunosuppressive macrophage marker CD163 was associated with shortened recurrence free survival. Using macrophage/chordoma co-culture, Delta-24-RGD infection achieved a reduction in macrophage expression of CD163. Taken together, Delta-24-RGD demonstrated efficacy in multiple models of chordoma including mice bearing CH22 tumors. The chordoma TME is associated with clinical outcomes and Delta-24-RGD infection reverses a deleterious immunosuppressive immune profile. These studies provide a framework for future clinical trial implementation for patients with metastatic or recurrent chordoma.

Assessment of P16 and Ki-67 Proteins Immunoexpressing in Oral Mucosa Among Saudi Smokers.

It is widely known that tobacco use significantly contributes to a variety of health problems, including mouth cancer. The proteins P16 and Ki-67 have a role in regulating the cell cycle and promoting cell growth. Analyzing the levels of these proteins can give us valuable information about the overall health of cells. This study aims to assess the cellular alterations and immunohistochemical expression of P16 and Ki-67 in the oral mucosa of Saudi smokers. From March to December 2023, a cross-sectional study scraped 500 samples from the buccal mucosa. Participants in the study were Saudi citizens of both genders. We selected a total of 300 individuals who smoked cigarettes and 200 individuals who did not smoke tobacco as the control group. The selection process involved two sample techniques: initially purposive sampling and subsequently snowball sampling. The samples underwent an immunohistochemical examination to determine the presence of P16 and Ki-67 protein overexpression. We evaluated the samples by assessing the proportion of cells that exhibited positive staining and the intensity of the staining. The data were examined utilizing SPSS. We identified categorical variables by calculating frequencies and percentages using the chi-squared test. A significance level of p < 0.05 was used to determine statistical significance. A total of 48% of cigarette users had abnormal results, compared to 20% of nonsmokers. These abnormalities included cytological atypia, inflammation, reverse cytological infection, and binucleated or multinucleated cells (p = 0.015). People who smoked had higher levels of P16 and Ki-67 expressions than people who did not smoke, 12% and 5%, respectively (p = 0.042). There were no important changes in P16/Ki-67 expression between participants of different ages (p = 0.68) or between men and women (p = 0.27). These results demonstrate the detrimental effects of smoking on cell health, underscoring the importance of quitting to reduce the risk of cytological abnormalities and related diseases. Smokers have higher levels of the proteins P16 and Ki-67, which shows how important these biomarkers are for understanding the risks to oral health.

HCMV strain- and cell type-specific alterations in membrane contact sites point to the convergent regulation of organelle remodeling.

Viruses are ubiquitous entities that infect organisms across the kingdoms of life. While viruses can infect a range of cells, tissues, and organisms, this aspect is often not explored in cell culture analyses. There is limited information about which infection-induced changes are shared or distinct in different cellular environments. The prevalent pathogen human cytomegalovirus (HCMV) remodels the structure and function of subcellular organelles and their interconnected networks formed by membrane contact sites (MCSs). A large portion of this knowledge has been derived from fibroblasts infected with a lab-adapted HCMV strain. Here, we assess strain- and cell type-specific alterations in MCSs and organelle remodeling induced by HCMV. Integrating quantitative mass spectrometry, super-resolution microscopy, and molecular virology assays, we compare infections with lab-adapted and low-passage HCMV strains in fibroblast and epithelial cells. We determine that, despite baseline proteome disparities between uninfected fibroblast and epithelial cells, infection induces convergent changes and is remarkably similar. We show that hallmarks of HCMV infection in fibroblasts, mitochondria-endoplasmic reticulum (ER) encapsulations and peroxisome proliferation, are also conserved in infected epithelial and macrophage-like cells. Exploring cell type-specific differences, we demonstrate that fibroblasts rely on endosomal cholesterol transport while epithelial cells rely on cholesterol from the Golgi. Despite these mechanistic differences, infections in both cell types result in phenotypically similar cholesterol accumulation at the viral assembly complex. Our findings highlight the adaptability of HCMV, in that infections can be tailored to the initial cell state by inducing both shared and unique proteome alterations, ultimately promoting a unified pro-viral environment.IMPORTANCEHuman cytomegalovirus (HCMV) establishes infections in diverse cell types throughout the body and is connected to a litany of diseases associated with each of these tissues. However, it is still not fully understood how HCMV replication varies in distinct cell types. Here, we compare HCMV replication with lab-adapted and low-passage strains in two primary sites of infection, lung fibroblasts and retinal epithelial cells. We discover that, despite displaying disparate protein compositions prior to infection, these cell types undergo convergent alterations upon HCMV infection, reaching a more similar cellular state late in infection. We find that remodeling of the subcellular landscape is a pervasive feature of HCMV infection, through alterations to both organelle structure-function and the interconnected networks they form via membrane contact sites. Our findings show how HCMV infection in different cell types induces both shared and divergent changes to cellular processes, ultimately leading to a more unified state.

Hyperexpression of PTAFR and PF4 as Possible Platelet Risk Biomarkers in Patients With COVID-19.

SARS-CoV-2 infection presents different severity levels that suggest the influence of genetic factors on the clinical outcome of the disease. In cases of severe COVID-19, the presence of elevated coagulation markers, increased platelet activation and aggregation and the risk of thrombotic complications are described. Given the participation of these cells in several serious viral infections and their negative role when associated with a prothrombotic response, it is important to understand the mechanistic role of SARS-CoV-2 in platelet physiology. This study evaluated the hyperexpression of platelet-activating factor receptor (PTAFR) and platelet factor 4 (PF4) in unvaccinated and hospitalized patients with COVID-19. The study included 43 COVID-19 patients stratified according to WHO guidelines. Subsequently, the expression of the PTAFR and PF4 genes were evaluated using the real-time quantitative PCR and their possible correlation with the severity of the disease and clinical variables including hospitalization, outcome, sex, age and laboratory parameters (platelet count, INR and D-dimer). The analysis demonstrated a significant (p<0.05) hyperexpression of these genes COVID-19 patients (n=43) compared to healthy controls. Expression of these genes in patients was not statistically significant (p>0.05) different between patients stratified according to clinical variables. The expression of PTAFR and PF4 suggests an important molecular pathway in the pathophysiology of the disease and may be valuable platelet biomarkers to indicate increased risk in patients with COVID-19 who require hospital care, contributing to personalized intervention strategies and improving their clinical management.

Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection.

Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A-positive (IgA+) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)-treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.