Infectious mononucleosis complicated by transitory Epstein-Barr virus infection of T and natural killer cells.

Epstein-Barr virus (EBV) typically infects B cells in infectious mononucleosis (IM), but a rare case shows EBV infection in T cells. Seven cases of lymphoproliferative disorder caused by EBV-positive cytotoxic T/natural killer (NK) cell proliferation in the lymph nodes, termed IM with transient EBV infection of T and NK cells (EBV + T/NK cells in IM), are reported here. The purpose of the study is to describe clinicopathological features of EBV + T/natural killer (NK) cells in IM of the lymph node. We retrospectively analysed seven cases of Chinese children and young people adults with EBV + T/NK cells in IM. We used morphological observation, immunohistochemical staining, EB virus in situ hybridisation detection, and analysis of T-cell receptor gene rearrangement. The patients were healthy prior to illness, experiencing sudden onset occurring in all the patients, with high fever as the first symptom, followed by lymphadenopathy and hepatosplenomegaly. Diagnosis occurred < 1.5 months of symptom onset. Most lymphocytes in lesions expressed CD3 and Granzyme B or TIA-1 and lacked CD5. CD56 was expressed in numerous cells in 5 of the 7 cases. EBV-encoded RNA (EBER) was detected in medium-to-large-sized cells (50-100 cells per cell/high-power field). T-cell receptor (TCR) gene rearrangement was seen in six cases, with monoclonal rearrangement in four cases. Treatment was conservative treatment but not chemotherapy. Four received anti-HLH therapy and others anti-inflammatory treatment. All patients survived with relapse after long-term clinical observation and follow-up. EBV + T/NK cells in IM can elicit malignant features that mimic T/NK-cell lymphoma pathologically and benign features mimicking IM clinically. These findings indicate that EBV + T/NK cells in IM could serve as valuable diagnosis. Additional clinical information, including age of onset (children and young people), nature of onset (sudden), disease course (short), symptoms (systemic), EBV infection status (acute), and lymph node involvement, is crucial for accurate diagnosis and prognostic evaluation.

Effects of COVID-19 Pandemic in Patients with a Previous Phrenic Nerve Transfer for a Traumatic Brachial Plexus Palsy.

Background With the advent of the coronavirus disease 2019 (COVID-19) pandemic, some doubts have been raised regarding the potential respiratory problems that patients who previously underwent a phrenic nerve transfer could have. Objectives To analyze the effects of the coronavirus infection on two populations, one from Argentina and another from Taiwan. Specific objectives were: (1) to identify the rate of COVID in patients with a history of phrenic nerve transfer for treatment of palsy; (2) to identify the overall symptom profile; (3) to compare Argentinian versus Taiwanese populations; and (4) to determine if any phrenic nerve transfer patients are at particular risk of more severe COVID. Methods A telephonic survey that included data regarding the number of episodes of acute COVID-19 infection, the symptoms it caused, the presence or absence of potential or life-threatening complications, and the status of COVID-19 vaccination were studied. Intergroup comparisons were conducted using the nonparametric Mann-Whitney U test, with categorical variables conducted using either the Pearson χ2 analysis or the Fisher's exact test, as appropriate. Results A total of 77 patients completed the survey, 40 from Taiwan and 37 from Argentina. Fifty-five (71.4%) developed a diagnosis of COVID. However, among these, only four had any level of dyspnea reported (4/55 = 7.3%), all mild. There were also no admissions to hospital or an intensive care unit, no intubations, and no deaths. All 55 patients isolated themselves at home. Conclusions It can be concluded that an acute COVID-19 infection was very well tolerated in our patients. (Level of evidence 3b, case reports).

Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption.

A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.

Proliferation in malaria parasites: How resource limitation can prevent evolution of greater virulence.

For parasites, robust proliferation within hosts is crucial for establishing the infection and creating opportunities for onward transmission. While faster proliferation enhances transmission rates, it is often assumed to curtail transmission duration by killing the host (virulence), a trade-off constraining parasite evolution. Yet in many diseases, including malaria, the preponderance of infections with mild or absent symptoms suggests that host mortality is not a sufficient constraint, raising the question of what restrains evolution toward faster proliferation. In malaria infections, the maximum rate of proliferation is determined by the burst size, the number of daughter parasites produced per infected red blood cell. Larger burst sizes should expand the pool of infected red blood cells that can be used to produce the specialized transmission forms needed to infect mosquitoes. We use a within-host model parameterized for rodent malaria parasites (Plasmodium chabaudi) to project the transmission consequences of burst size, focusing on initial acute infection where resource limitation and risk of host mortality are greatest. We find that resource limitation restricts evolution toward higher burst sizes below the level predicted by host mortality alone. Our results suggest resource limitation could represent a more general constraint than virulence-transmission trade-offs, preventing evolution towards faster proliferation.

Bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus infection: a case report.

BACKGROUND: To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement. CASE PRESENTATION: A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates. CONCLUSIONS: In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.

Hepatitis B virus reactivation in patients treated with monoclonal antibodies.

Hepatitis B virus (HBV) reactivation poses a significant clinical challenge, especially in patients undergoing immunosuppressive therapies, including monoclonal antibody treatments. This manuscript briefly explores the complex relationship between monoclonal antibody therapy and HBV reactivation, drawing upon current literature and clinical case studies. It delves into the mechanisms underlying this phenomenon, highlighting the importance of risk assessment, monitoring, and prophylactic measures for patients at risk. The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy, ultimately facilitating informed clinical decision-making and improved patient care. This paper will also briefly review the definition of HBV activation, assess the risks of reactivation, especially in patients treated with monoclonal antibodies, and consider management for patients with regard to screening, prophylaxis, and treatment. A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.

Seromolecular study on the prevalence and risk factors of Toxoplasma gondii infection in pregnant women referred to a gynecology hospital in Urmia, northwest part of Iran in 2022.

Toxoplasmosis is a frequent infection among the human population. The infection can cause devastating complications for the fetus during pregnancy. The present study aimed to determine the serological and molecular prevalence of the infection and molecular characterization of Toxoplasma gondii isolates among pregnant women referred to Kowsar Hospital, Urmia, Iran. In a cross-sectional study, 340 blood samples were collected from pregnant women referred to Kowsar Hospital, Urmia, Iran from May to July 2022. Anti-T. gondii IgG and IgM seropositivity were determined by enzyme-linked immunosorbent assay. PCR was carried out by targeting the GRA6 gene of the parasite on all patients' buffy coats. Anti-T. gondii IgG and IgM antibodies were positive in two (0.6%) women, and 101 (29.7%) women had anti-T. gondii IgG and 70.3% were seronegative. PCR was positive in two IgM-positive women, and both isolates belonged to T. gondii carrying the GRA6 allele of lineage I. The risk of infection was significantly higher in women who had constant contact with cats and soil, and who were residents of rural areas. The two IgM-positive women were asymptomatic regarding acute toxoplasmosis. According to the results of the present study, the prevalence of toxoplasmosis in pregnant women in Urmia is similar to its prevalence in other areas in northwestern Iran, and despite the low prevalence of acute infection, it should not be ignored.

Phosphatidylserine synthase in the endoplasmic reticulum of Toxoplasma is essential for its lytic cycle in human cells.

Glycerophospholipids have emerged as a significant contributor to the intracellular growth of pathogenic protist Toxoplasma gondii. Phosphatidylserine (PtdSer) is one such lipid, attributed to the locomotion and motility-dependent invasion and egress events in its acutely infectious tachyzoite stage. However, the de novo synthesis of PtdSer and the importance of the pathway in tachyzoites remain poorly understood. We show that a base-exchange-type PtdSer synthase (PSS) located in the parasite's endoplasmic reticulum produces PtdSer, which is rapidly converted to phosphatidylethanolamine (PtdEtn) by PtdSer decarboxylase (PSD) activity. The PSS-PSD pathway enables the synthesis of several lipid species, including PtdSer (16:0/18:1) and PtdEtn (18:2/20:4, 18:1/18:2 and 18:2/22:5). The PSS-depleted strain exhibited a lower abundance of the major ester-linked PtdEtn species and concurrent accrual of host-derived ether-PtdEtn species. Most phosphatidylthreonine (PtdThr) species-an exclusive natural analog of PtdSer, also made in the endoplasmic reticulum-were repressed. PtdSer species, however, remained largely unaltered, likely due to the serine-exchange reaction of PtdThr synthase in favor of PtdSer upon PSS depletion. Not least, the loss of PSS abrogated the lytic cycle of tachyzoites, impairing the cell division, motility, and egress. In a nutshell, our data demonstrate a critical role of PSS in the biogenesis of PtdSer and PtdEtn species and its physiologically essential repurposing for the asexual reproduction of a clinically relevant intracellular pathogen.

Epigenetic Control of Innate Immunity: Consequences of Acute Respiratory Virus Infection.

Infections caused by acute respiratory viruses induce a systemic innate immune response, which can be measured by the increased levels of expression of inflammatory genes in immune cells. There is growing evidence that these acute viral infections, alongside transient transcriptomic responses, induce epigenetic remodeling as part of the immune response, such as DNA methylation and histone modifications, which might persist after the infection is cleared. In this article, we first review the primary mechanisms of epigenetic remodeling in the context of innate immunity and inflammation, which are crucial for the regulation of the immune response to viral infections. Next, we delve into the existing knowledge concerning the impact of respiratory virus infections on the epigenome, focusing on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza A Virus (IAV), and Respiratory Syncytial Virus (RSV). Finally, we offer perspectives on the potential consequences of virus-induced epigenetic remodeling and open questions in the field that are currently under investigation.

Comparative analysis of antibiotic susceptibility patterns and clinical features of mucoid and non-mucoid Pseudomonas aeruginosa infections: a retrospective study.

Background: Pseudomonas aeruginosa (PA) is a prevalent opportunistic pathogen that has close associations with both acute and chronic infections. However, there exists an insufficiency of accurate and comprehensive data pertaining to the antimicrobial susceptibility patterns and clinical characteristics of both mucoid and non-mucoid strains of PA (mPA and non-mPA, respectively). Methods: From January 1, 2021 to December 31, 2022, a thorough retrospective study was carried out to examine and compare the antibiotic susceptibility test outcomes and clinical characteristics of hospitalized patients with mPA and non-mPA infections. Results: This study investigated a cohort of 111 patients who were diagnosed with mPA infections, as well as 792 patients diagnosed with non-mPA infections. Significant demographic disparities, including gender (p < 0.001), age (p < 0.001), length of hospital stay (p < 0.001), diabetes (p = 0.043), and hypertension (p < 0.001), are evident between the mPA and non-mPA groups. The mPA group commonly necessitates hospitalization for respiratory system diseases, whereas the non-mPA group is associated with concomitant cardiovascular and cerebrovascular diseases. The mPA group demonstrates lower utilization rates of medical devices, such as Foley catheter (p < 0.001), nasogastric tube (p < 0.001), mechanical ventilation (p < 0.001), tracheostomy (p < 0.001), arterial and venous catheterization (p < 0.001), and exhibits superior organ function status, including lower incidences of hypoalbuminemia (p < 0.001), septic shock (p < 0.001), liver dysfunction (p < 0.001), renal failure (p < 0.001), and respiratory failure (p < 0.001). The non-mPA group is more vulnerable to infection with two or more bacterial pathogens compared to the mPA group, with the non-mPA group frequently resulting in Enterobacteriaceae infections and the mPA group being associated with fungal infections. Variations in antibiotic sensitivity are noted for Amikacin (p < 0.001), Ciprofloxacin (p < 0.001), Cefepime (p = 0.003), and Levofloxacin (p < 0.001) in antibiotic susceptibility testing, with resistance patterns closely tied to specific antibiotic usage. Conclusion: There are significant demographic characteristics, clinical manifestations and antibiotic susceptibility between mPA and non-mPA infections. It is crucial to emphasize these characteristics due to their significant role in preventing and treating PA infections.

Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision.

The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, quantitative live imaging, and an acute infection model, we find that T cells will maintain or lose memory potential early after antigen recognition. However, following pathogen clearance, T cells may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1, in response to stimulation. Mathematical modeling shows how this flexibility allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decisions ensure optimal immune responses against diverse threats.

Higher diagnostic value of metagenomic next-generation sequencing in acute infection than chronic infection: a multicenter retrospective study.

Background: The aim of this study is to compare the diagnostic value of metagenomic next-generation sequencing (mNGS) vs. conventional culture methods (CM) in chronic infection and acute infection. Methods: We retrospectively analyzed the bronchoalveolar lavage fluid (BALF) of 88 patients with acute infection and 105 patients with chronic infection admitted to three hospitals from 2017 to 2022. Results: The results showed that the sensitivity and specificity of mNGS were higher than those of CM. The number of patients who changed the antibiotic treatment in the mNGS positive group was larger than that of patients in the mNGS negative group in both the acute infection group (60.5 vs. 28.0%, P = 0.0022) and chronic infection group (46.2 vs. 22.6%, P = 0.01112). High levels of temperature (OR: 2.02, 95% CI: 1.18-3.70, P: 0.015), C-reactive protein (CRP) (OR: 15, 95% CI: 2.74-280.69, P: 0.011), neutrophil count (OR: 3.09, 95% CI: 1.19-8.43, P: 0.023), and low levels of lymphocyte count (OR: 3.43, 95% CI:1.26-10.21, P: 0.020) may lead to positive mNGS results in the acute infection group while no significant factor was identified to predict positive results in the chronic infection group. Conclusion: mNGS could provide useful guidance on antibiotic strategies in infectious diseases and may be more valuable for the diagnosis and treatment of acute infection vs. chronic infection.

c.202_204del in NUP214 causes late onset form of febrile encephalopathy.

Nucleoporins (NUPs) are a group of transporter proteins that maintain homeostasis of nucleocytoplasmic transport of proteins and ribonucleic acids under physiological conditions. Biallelic pathogenic variants in NUP214 are known to cause susceptibility to acute infection-induced encephalopathy-9 (IIAE9, MIM#618426), which is characterized by severe and early-onset febrile encephalopathy causing neuroregression, developmental delay, microcephaly, epilepsy, ataxia, brain atrophy, and early death. NUP214-related IIAE9 has been reported in eight individuals from four distinct families till date. We identified a novel in-frame deletion, c.202_204del p.(Leu68del), in NUP214 by exome sequencing in a 20-year-old male with episodic ataxia, seizures, and encephalopathy, precipitated by febrile illness. Neuroimaging revealed progressive cerebellar atrophy. In silico predictions show a change in the protein conformation that may alter the downstream protein interactions with the NUP214 N-terminal region, probably impacting the mRNA export. We report this novel deletion in NUP214 as a cause for a late onset and less severe form of IIAE9.

Endogenous origin of Pseudomonas aeruginosa infecting hospitalized patients in Ecuador.

Recent evidence suggests that Pseudomonas aeruginosa, a bacterium that has the ability to cause deadly infections in hospitalized patients, could originate in the patient's own flora. We employed the Oxford Nanopore platform to obtain whole genome sequences (WGS) from clinical and rectal screen P. aeruginosa strains belonging to 15 patients from two hospitals. Our study found evidence that clinical and rectal isolates were clonal, with some evidence suggesting that the infecting strain was present in the patient's intestine at the time of admission, ruling out hospital acquisition. The use of WGS analysis is crucial to detect alternative sources of P. aeruginosa to develop new preventive measures against these serious infections.

Detection of feline morbillivirus in cats with symptoms of acute febrile infection.

Feline morbillivirus (FeMV) was identified for the first time in cats in 2012 in Hong Kong. Although its association with chronic kidney disease in cats has attracted the attention of researchers, its clinical significance as an acute infection has not been reported. Previously, we reported FeMV detection using next-generation sequence-based comprehensive genomic analysis of plasma samples from cats with suspected acute febrile infections. Here, we conducted an epidemiological survey to detect FeMV by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using blood samples from cats in Japan. FeMV was detected in 32/102 blood samples (31.4%) from cats with suspected acute viral infections. Most of the FeMV-positive cats had clinical findings consistent with acute viral infections, including fever, leukopenia, thrombocytopenia and jaundice. No FeMV was detected in healthy cats or clinically ill cats that visited veterinary hospitals. Phylogenetic analysis classified FeMV L genes into various FeMV subtypes. We also necropsied a FeMV-positive cat that died of a suspected acute infection. On necropsy, FeMV was detected in systemic organs, including the kidneys, lymph nodes and spleen by qRT-PCR and immunohistochemical staining. These results suggest that FeMV infections may cause acute symptomatic febrile infections in cats. A limitation of this study was that the involvement of other pathogens that cause febrile illnesses could not be ruled out and this prevented a definitive conclusion that FeMV causes febrile disease in infected cats. Further studies that include experimental infections are warranted to determine the pathogenicity of FeMV in cats.

Cytokine profile, neutralisation potential and viral replication dynamics in sera of chikungunya patients in India: a cross-sectional study.

Background: Chikungunya disease (CHIKD) is a threat to global health, as it impairs the quality of life of an infected individual ranging from months to years. A systematic evaluation of the serological, virological, and immunological aspects of the circulating viruses and their impact on the host response is imperative for better understanding of the evolving disease dynamics. Methods: Serum samples were collected from 196 acute CHIKD patients from ten tertiary care hospitals across India during 2016-2021. Out of 196 patients, paired convalescent samples were collected from 51 patients (one-month post-onset of symptoms). The serum samples were profiled for cytokines and neutralisation capacity. Further, chikungunya virus (CHIKV) was isolated from the acute sera and the replication kinetics of the clinical isolates was evaluated. Findings: Serological analysis indicated that neutralisation could be correlated to seroconversion in the convalescent phase but not found significant in acute phase. In the acute phase samples, there was a correlation between elevated serum levels of IFN-γ, IP-10, MCP-1 and MIG and disease severity. During convalescent phase, pro-inflammatory markers such as IL-6, IL-1ß, IL-9 and IP-10 were found to be elevated with a corresponding decline in the secretion of anti-inflammatory cytokines such as IL-4 and IL-10, which correlated with persistent arthralgia. Analysis of replication of the clinical isolates revealed that 68.4% of viruses were fast-growing in the Vero cells (cytopathic effect [CPE] observed within 24 h post-infection), and their corresponding acute serum samples showed an elevated secretion of IFN-α, IL-1RA, IL-17F, IL-9, MCP-1 and MIP-1α. Interpretation: This study provides an important overview of neutralisation capabilities and cytokine responses along with virus pathogenesis associated with CHIKV infections in India. Funding: Biotechnology Industry Research Assistance Council (BIRAC).

Exploring Viral Metagenomics in Pediatric Patients with Acute Respiratory Infections: Unveiling Pathogens beyond SARS-CoV-2.

The emergence of SARS-CoV-2 and the subsequent pandemic have prompted extensive diagnostic and clinical efforts to mitigate viral spread. However, these strategies have largely overlooked the presence of other respiratory viruses. Acute respiratory diseases in pediatric patients can be caused by a diverse range of viral agents, and metagenomics represents a powerful tool for their characterization. This study aimed to investigate the viral abundance in pediatric patients with acute respiratory symptoms who tested negative for SARS-CoV-2 during the Omicron pandemic wave. To achieve this, viral metagenomics and next-generation sequencing were employed on 96 nasopharyngeal swab samples, which were organized into 12 pools, with each pool consisting of eight individual samples. Metagenomic analysis revealed that the most prevalent viruses associated with acute disease in pediatric patients were respiratory syncytial virus (detected in all pools) and enteroviruses, which are known to cause significant morbidity and mortality in children. Additionally, clinically significant viruses such as mumps orthorubulavirus, human metapneumovirus, influenza A, and a wide array of human herpesviruses (1, 3-7) were identified. These findings highlight the extensive potential of viral metagenomics in identifying viruses other than SARS-CoV-2 that contribute to acute infections in children. Consequently, this methodology should garner clinical attention in terms of differential diagnosis and the development of public policies to address such conditions in the global pediatric population.

Short- and longer-term all-cause mortality among SARS-CoV-2- infected individuals and the pull-forward phenomenon in Qatar: a national cohort study.

OBJECTIVES: We assessed short-, medium-, and long-term all-cause mortality risks after a primary SARS-CoV-2 infection. METHODS: A national, matched, retrospective cohort study was conducted in Qatar to assess risk of all-cause mortality in the national SARS-CoV-2 primary infection cohort compared with the national infection-naïve cohort. Associations were estimated using Cox proportional-hazards regression models. Analyses were stratified by vaccination status and clinical vulnerability status. RESULTS: Among unvaccinated persons, within 90 days after primary infection, the adjusted hazard ratio (aHR) comparing mortality incidence in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% confidence interval 1.02-1.39). aHR was 1.34 (1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (0.72-1.24) in those less clinically vulnerable. Beyond 90 days after primary infection, aHR was 0.50 (0.37-0.68); aHR was 0.41 (0.28-0.58) at 3-7 months and 0.76 (0.46-1.26) at ≥8 months. The aHR was 0.37 (0.25-0.54) in more clinically vulnerable persons and 0.77 (0.48-1.24) in less clinically vulnerable persons. Among vaccinated persons, mortality incidence was comparable in the primary-infection versus infection-naïve cohorts, regardless of clinical vulnerability status. CONCLUSIONS: COVID-19 mortality was primarily driven by an accelerated onset of death among individuals who were already vulnerable to all-cause mortality, but vaccination prevented these accelerated deaths.

Transcriptome analysis reveals the neuroactive receptor genes response to Streptococcus agalactiae infection in tilapia, Oreochromis niloticus.

The detailed crosstalk between the neuroendocrine and immune systems in Oreochromis niloticus, an economically important fish, in response to pathogenic infections, remains unclear. This study revealed the head kidney transcriptional profiles of O. niloticus upon infections with Streptococcus agalactiae, a prevalent pathogen known to cause severe meningitis. Twelve cDNA libraries of O. niloticus head kidney, representing four treatment time points (0, 6, 24, and 48 h), were constructed and a total of 2,528 differentially expressed genes were identified based on pairwise comparisons. KEGG pathway analysis revealed a significant enrichment of the 'neuroactive ligand-receptor interaction' pathway (ko04080), with 13 genes exhibiting differential expression during S. agalactiae infection. Among these, six neuroactive receptor genes (lepr, nr3c1, ptger4, thrb, tspo, and ß2-ar) were selected, cloned, and characterized. Although these genes are ubiquitously expressed, and in head kidney leukocytes, their expression was mainly observed in T cells, Mo/Mφ, and NCCs, which are characterized by antimicrobial responses. Furthermore, we examined the response patterns of these six neuroactive receptor genes to gram-positive (S. agalactiae) and gram-negative (Aeromonas hydrophila) bacteria in four different tissues. Notably, lepr, ptger4, tspo, and ß2-ar were upregulated in all selected tissues in response to S. agalactiae and A. hydrophila infections. However, nr3c1 and thrb were downregulated in response to S. agalactiae infection in the head kidney and spleen, whereas nr3c1 was upregulated, and thrb was unresponsive to A. hydrophila infection. Our findings provide a theoretical foundation for understanding new links between the neuroendocrine and immune systems during bacterial infection in teleost fish.

Kinetics of TTV Loads in Peripheral Blood Mononuclear Cells of Early Treated Acute HIV Infections.

Torquetenovirus (TTV) is the most abundant component of the human blood virome and its replication is controlled by a functioning immune system. In this study, TTV replication was evaluated in 21 people with acute HIV infection (AHI) and immune reconstitution following antiretroviral therapy (ART). PBMC-associated TTV and HIV-1 DNA, as well as plasma HIV-1 RNA, were measured by real-time PCR. CD4 and CD8 differentiation, activation, exhaustion, and senescence phenotypes were analyzed by flow cytometry. Thirteen healthy donors (HD) and twenty-eight chronically infected HIV individuals (CHI), late presenters at diagnosis, were included as control groups. TTV replication in AHI seems to be controlled by the immune system being higher than in HD and lower than in CHI. During ART, a transient increase in TTV DNA levels was associated with a significant perturbation of activation and senescence markers on CD8 T cells. TTV loads were positively correlated with the expansion of CD8 effector memory and CD57+ cells. Our results shed light on the kinetics of TTV replication in the context of HIV acute infection and confirm that the virus replication is strongly regulated by the modulation of the immune system.