Later Stages Of Infection Research Articles

Plasma galectin-9 levels correlate with blood monocyte turnover and predict simian/human immunodeficiency virus disease progression

Abstract Background Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline associated with progression to terminal disease. High MTO is associated with increased tissue macrophage death. However, MTO analysis is complex and not directly applicable to humans. Methods We explored blood-available biomarkers associated with MTO using comprehensive immune cell profiling via flow cytometry, blood cell count and chemistry, and ELISA. Results Plasma galectin-9 was identified as the most highly correlated marker with MTO. This correlation remained statistically significant during acute, chronic, and late-stage infections caused by three different SIV strains tested. In addition, the galectin-9 level also predicted decline in animal health, requiring medical cull. The correlation between MTO and galectin-9 was maintained even in uninfected animals showing variable MTO. Conclusions These findings support the exploration of galectin-9 as a surrogate biomarker of MTO for non-invasive monitoring of disease progression (e.g. HIV) that may also be applicable in humans and as a potential indicator of tissue macrophages apoptosis.

First report of powdery mildew on Vigna unguiculata caused by Podosphaera xanthii in China.

Vigna unguiculata belongs to the Legume family, and is an annual twining, herbaceous vine plant, which is native to Africa. V. unguiculata is the most economically beneficial type of off-season vegetables in Hainan, China because of its rich in nutrients such as protein, minerals, dietary fiber, and vitamins (Jayathilake et al. 2018). In April 2022, typical powdery mildew infection was observed on V. unguiculata leaves in Haikou, Hainan Province, China (20°3'40.428"N, 110°19'45.217"E). More than 70% leaves of 13 V. unguiculata plants displayed severe powdery mildew disease. The diseased leaves at first exhibited white rounded irregular patches, which gradually enlarged, fused and covered all the leaf as well as stems. Edges of the infected leaves crinkled upwards, and the leaves often fell off the plants at the late infection stage. On the infected leaves, many conidiophores and dense mycelium were observed by microscopic analysis. Hyphae were septate, branched, epigenous, and flexuous to straight. Hyphal appressoria were indistinct or slightly nipple-shaped, and the haustoria developed were in the shape of oval-sphere and 9 to 11μm long. Foot cells of conidiophores were straight, cylindrical, and measured 43 to 70 × 10 to 12 μm. The conidiophores arising straightly from a hyphal cell, were measured 168 to 252 (mean = 204) μm in length and produced 6 to 9 immature conidia in each chain. Conidia were ovate, pyriform or barrel-shaped, with fibrosin bodies, and measured 26 to 32 (mean = 29.4) × 16 to 20 (mean = 18.6) μm. The chasmothecia was not found in all samples. These morphological characteristics were typical of the conidial stage of the powdery mildew Podosphaera xanthii of genus Podosphaera (Braun and Cook 2012). To further confirm the identity of this causal fungus, the internal transcribed spacer (ITS) region, and the partial sequence of large subunit ribosomal RNA gene (28S rRNA), were amplified with primer pairs ITS1/ ITS4 (White et al. 1990) and NL1/NLP2 (Mori et al. 2000) from extracted genomic DNA. The obtained 563-bp ITS region and 715-bp 28S rRNA gene sequences were deposited in GenBank (ITS, OQ415534; 28S rRNA, OQ415545.1), and were compared with BLAST analysis in the GenBank nr database. The results revealed that the ITS region sequence was 99.82% identity with P. xanthii isolate HUVU-08 (MH143485.1), and the 28S rRNA gene partial sequence was 100% identity with P. xanthii isolate XHL1 (MK357442.1). On the basis of the morphological characteristics and sequence analysis, this fungus was identified as P. xanthii. Pathogenicity tests were performed by gently brushing conidia onto the leaves of six healthy potted V. unguiculata plants. Six non-inoculated plants were used as control. All plants were maintained in a greenhouse at 26 ± 2°C. After 2 weeks inoculation, similar symptoms were observed in the inoculated plants, whereas no symptoms occurred on the control plants. By microscopic observation, the fungus present on the inoculated plants was morphologically identical to those on originally diseased plants. Furthermore, ITS and 28S rRNA sequences of the re-isolated fungus individually displayed 100% identity with OQ415534 and OQ415545.1. So far, although powdery mildew disease caused by P. xanthii on different plants including Sigesbeckia orientalis (Mukhtar et al. 2022), Vigna radiata (Sheu et al. 2021), Cosmos bipinnatus (Kong et al. 2023), Verbena brasiliensis (Luecke et al. 2020), Cucurbita ficifolia (Choi et al. 2022), Glandularia tenera (Pei et al. 2023) and Verbena bonariensis (Choi et al. 2023) have been reported, to our knowledge, this is the first report of powdery mildew caused by P. xanthii on V. unguiculata in Hainan, China, which seriously threatens the utilization of V. unguiculata on off-season vegetables industry.

Proteomics and Metabolomics in Congenital Zika Syndrome: A Review of Molecular Insights and Biomarker Discovery.

Zika virus (ZIKV) infection can be transmitted vertically, leading to the development of congenital Zika syndrome (CZS) in infected fetuses. During the early stages of gestation, the fetuses face an elevated risk of developing CZS. However, it is important to note that late-stage infections can also result in adverse outcomes. The differences between CZS and non-CZS phenotypes remain poorly understood. In this review, we provide a summary of the molecular mechanisms underlying ZIKV infection and placental and blood-brain barriers trespassing. Also, we have included molecular alterations that elucidate the progression of CZS by proteomics and metabolomics studies. Lastly, this review comprises investigations into body fluid samples, which have aided to identify potential biomarkers associated with CZS.

ТУБЕРКУЛЕЗ ЛЕГКИХ У БОЛЬНЫХ ВИЧ-ИНФЕКЦИЕЙ НА ПОЗДНИХ СТАДИЯХ И ПСИХИЧЕСКИМИ ЗАБОЛЕВАНИЯМИ

According to the data of a retrospective assessment of the medical histories of 238 patients, the features of the clinical course of pulmonary tuberculosis in patients with late-stage HIV infection and mental pathology in various morbid variants are considered in a comparative aspect. The data on age-sex and social characteristics, clinical, radiological and bacteriologicalfeatures of the course of the disease in the observed patients are presented. It was found that disseminated (39.4%) and generalized (24.5%) forms of the disease prevailed in patients with pulmonary tuberculosis and late-stage HIV infection in combination with mental illnesses. Bacterioexcretion was observed in 60.6% of patients, including 70.2% of patients with multidrug-resistant tuberculosis and 44.7% of patients with cavities. Distinctive clinical and radiological signs of the course of tuberculosis in patients with various comorbid variants of these nosologies are presented, which is essential for the development of patient-oriented management programs and improvement of treatment effectiveness in these severe categories of patients.

Ectromelia Virus Affects the Formation and Spatial Organization of Adhesive Structures in Murine Dendritic Cells In Vitro.

Ectromelia virus (ECTV) is a causative agent of mousepox. It provides a suitable model for studying the immunobiology of orthopoxviruses, including their interaction with the host cell cytoskeleton. As professional antigen-presenting cells, dendritic cells (DCs) control the pericellular environment, capture antigens, and present them to T lymphocytes after migration to secondary lymphoid organs. Migration of immature DCs is possible due to the presence of specialized adhesion structures, such as podosomes or focal adhesions (FAs). Since assembly and disassembly of adhesive structures are highly associated with DCs' immunoregulatory and migratory functions, we evaluated how ECTV infection targets podosomes and FAs' organization and formation in natural-host bone marrow-derived DCs (BMDC). We found that ECTV induces a rapid dissolution of podosomes at the early stages of infection, accompanied by the development of larger and wider FAs than in uninfected control cells. At later stages of infection, FAs were predominantly observed in long cellular extensions, formed extensively by infected cells. Dissolution of podosomes in ECTV-infected BMDCs was not associated with maturation and increased 2D cell migration in a wound healing assay; however, accelerated transwell migration of ECTV-infected cells towards supernatants derived from LPS-conditioned BMDCs was observed. We suggest that ECTV-induced changes in the spatial organization of adhesive structures in DCs may alter the adhesiveness/migration of DCs during some conditions, e.g., inflammation.

NDV inhibited IFN-β secretion through impeding CHCHD10-mediated mitochondrial fusion to promote viral proliferation

Newcastle disease virus (NDV) is an RNA virus that can promote its own replication through the inhibition of cellular mitochondrial fusion. The proteins involved in mitochondrial fusion, namely mitofusin 1 (Mfn1) and optic atrophy 1 (OPA1) are associated with interferon-beta (IFN-β) secretion during NDV infection. However, the precise mechanism by which NDV modulates the Mfn1-mediated or OPA1-mediated fusion of mitochondria, thereby impacting IFN-β, remains elusive. This study revealed that the downregulation of the mitochondrial protein known as coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) exerts a negative regulatory effect on OPA1 and Mfn1 in human lung adenocarcinoma (A549) cells during the late stage of NDV infection. This reduction in CHCHD10 expression impeded cellular mitochondrial fusion, subsequently leading to a decline in the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB), ultimately resulting in diminished secretion of IFN-β. In contrast, the overexpression of CHCHD10 alleviated infection-induced detrimental effect in mitochondrial fusion, thereby impeding viral proliferation. In summary, NDV enhances its replication by inhibiting the CHCHD10 protein, which impedes mitochondrial fusion and suppresses IFN-β production through the activation of IRF3 and NF-κB.

Characteristics and risk assessment of cryptocaryoniasis in large yellow croaker (Larimichthys crocea) at different densities in industrialized aquaculture

With the introduction and advancement of sustainable development in aquaculture, traditional fish farming methods are gradually transitioning to advanced industrial farming models. To explore the occurrence patterns and risks of cryptocaryoniasis in industrialized high-density aquaculture, we used a non-lethal dose of Cryptocaryon irritans theronts (400 theronts/m3) to infect Larimichthys crocea at different rearing densities [low-density group (0.088 kg/m3), medium-density group (0.88 kg/m3), and high-density group (8.80 kg/m3)]. We explored the relationship between L. crocea density and the growth rate of the C. irritans population by observing the differences in growth, feeding, and survival rates of the L.crocea in each group and the changes in water quality and the number of C. irritans tomonts during the rearing process. We also evaluated the risks associated with the occurrence of cryptocaryoniasis in aquaculture. The results showed significant differences in the relative levels of the first round of infection among different density groups of L.crocea, which affected the outbreak speed of cryptocaryoniasis and the maximum relative tomont number (RTN) of L. crocea. Specifically, the outbreak speed of cryptocaryoniasis from fast to slow was as follows: medium-density group>low-density group>high-density group. The RTN when all L.crocea had died in each group was 12.82 (medium-density group), 49.7 (low-density group), and 106.58 (high-density group). The occurrence of cryptocaryoniasis reduced the feeding and growth rates of L.crocea in all groups, and the effect was most pronounced in the second week and the late stages of infection. The occurrence of cryptocaryoniasis caused abnormal swimming behavior in all three density groups. The main manifestations of C. irritans infection in L. crocea included rubbing the snout against the barrel wall, body imbalance, dispersed swimming, and delayed responses. The deterioration of water quality was most pronounced in the high-density group, but the outbreak speed of cryptocaryoniasis was the slowest in the high-density group, suggesting that no significant correlation existed between the deterioration of water quality and the outbreak speed of cryptocaryoniasis. The outbreak speed of cryptocaryoniasis varies depending on the fish-rearing density, and the progression and risk of cryptocaryoniasis are not proportionally correlated with the rearing density of L. crocea.

A nematode-inducible promoter can effectively drives RNAi construct to confer Meloidogyne incognita resistance in tomato.

Heterologous expression of a nematode-responsive promoter in tomato successfully driven the RNAi constructs to impart root-knot nematode resistance. The root-knot nematode Meloidogyne incognita seriously afflicts the global productivity of tomatoes. Nematode management options are extremely reliant on chemical methods, however, only a handful of nematicides are commercially available. Additionally, nematodes have developed resistance-breaking phenotypes against the commercially available Mi gene-expressing tomatoes. Nematode resistance in crop plants can be enhanced using the bio-safe RNAi technology, in which plants are genetically modified to express nematode gene-specific dsRNA/siRNA molecules. However, the majority of the RNAi crops conferring nematode tolerance have used constitutive promoters, which have many limitations. In the present study, using promoter-GUS fusion, we functionally validated two nematode-inducible root-specific promoters (pAt1g74770 and pAt2g18140, identified from Arabidopsis thaliana) in the Solanum lycopersicum-M. incognita pathosystem. pAt2g18140 was found to be nematode-responsive during 10-21days post-inoculation (dpi) and became non-responsive during the late infection stage (28 dpi). In contrast, pAt1g74770 remained nematode-responsive for a longer duration (10-28 dpi). Next, a number of transgenic lines were developed that expressed RNAi constructs (independently targeting the M. incognita integrase and splicing factor genes) driven by the pAt1g74770 promoter. M. incognita parasitic success (measured by multiplication factor ratio) in pAt1g74770:integrase and pAt1g74770:splicing factor RNAi lines were significantly reduced by 60.83-74.93% and 69.34-75.31%, respectively, compared to the control. These data were comparable with the RNAi lines having CaMV35S as the promoter. Further, a long-term RNAi effect was evident, because females extracted from transgenic lines were of deformed shape with depleted transcripts of integrase and splicing factor genes. We conclude that pAt1g74770 can be an attractive alternative to drive localized expression of RNAi constructs rather than using a constitutive promoter. The pAt1g74770-driven gene silencing system can be expanded into different plant-nematode interaction models.

Cell death induction facilitates egress of Coxiella burnetii from infected host cells at late stages of infection.

Intracellular bacteria have evolved mechanisms to invade host cells, establish an intracellular niche that allows survival and replication, produce progeny, and exit the host cell after completion of the replication cycle to infect new target cells. Bacteria exit their host cell by (i) initiation of apoptosis, (ii) lytic cell death, and (iii) exocytosis. While bacterial egress is essential for bacterial spreading and, thus, pathogenesis, we currently lack information about egress mechanisms for the obligate intracellular pathogen C. burnetii, the causative agent of the zoonosis Q fever. Here, we demonstrate that C. burnetii inhibits host cell apoptosis early during infection, but induces and/or increases apoptosis at later stages of infection. Only at later stages of infection did we observe C. burnetii egress, which depends on previously established large bacteria-filled vacuoles and a functional intrinsic apoptotic cascade. The released bacteria are not enclosed by a host cell membrane and can infect and replicate in new target cells. In summary, our data argue that C. burnetii egress in a non-synchronous way at late stages of infection. Apoptosis-induction is important for C. burnetii egress, but other pathways most likely contribute.

Biomimetic Targeting Nanoadjuvants for Sonodynamic and Chronological Multi-Immunotherapy against Holistic Biofilm-Related Infections.

Biofilm-related infections (BRIs) present significant challenges owing to drug resistance, adverse immune responses, and implant failure; however, current approaches inadequately cater to the diverse therapeutic requirements at different stages of infection. To address this issue, a multi-immunotherapy strategy in combination with sonodynamic therapy is proposed for the chronological treatment of BRIs. Macrophage membrane-decorated targeting sonosensitive nanoadjuvants are fabricated to load cytosine-phosphate-guanine oligodeoxynucleotide (CPG-ODN) or microRNA (miR)-21-5p. In the early stages of BRI (Stage I), CPG-ODN-loaded nanoadjuvants (CPG@HMPN@M) promote the formation of neutrophil extracellular traps to capture and neutralize detached microbes. During the late stage of infection (Stage II), CPG-ODNs redirect macrophage polarization into the M1 phase to combat infections via TLR9/Myd88/TRAF6 pathway. During these stages, CPG@HMPN@M generates singlet oxygen through sonodynamic processes, eradicating the biofilms under US irradiation. Once the BRIs are eliminated, miR-21-5p-loaded nanoadjuvants (miR@HMPN@M) are delivered to the lesions to suppress excessive inflammation and promote tissue integration by evoking macrophage M2 polarization during the repair phase (Stage III) through PTEN/PI3K/Akt pathway. This innovative approach aims to provide comprehensive treatment strategies for the chronological treatment of BRI by effectively eliminating infections, promoting tissue restoration, and implementing different immune regulations at different stages, thus demonstrating promising clinical value.

Plant hypersensitive induced reaction protein facilitates cell death induced by secreted xylanase associated with the pathogenicity of Sclerotinia sclerotiorum.

Necrotrophic fungal plant pathogens employ cell death-inducing proteins (CDIPs) to facilitate infection. However, the specific CDIPs and their mechanisms in pathogenic processes of Sclerotinia sclerotiorum, a necrotrophic pathogen that causes disease in many economically important crop species, have not yet been clearly defined. This study found that S. sclerotiorum secretes SsXyl2, a glycosyl hydrolase family 11 xylanase, at the late stage of hyphal infection. SsXyl2 targets the apoplast of host plants to induce cell death independent of xylanase activity. Targeted disruption of SsXyl2 leads to serious impairment of virulence, which can be recovered by a catalytically impaired SsXyl2 variant, thus supporting the critical role of cell death-inducing activity of SsXyl2 in establishing successful colonization of S. sclerotiorum. Remarkably, infection by S. sclerotiorum induces the accumulation of Nicotiana benthamiana hypersensitive-induced reaction protein 2 (NbHIR2). NbHIR2 interacts with SsXyl2 at the plasma membrane and promotes its localization to the cell membrane and cell death-inducing activity. Furthermore, gene-edited mutants of NbHIR2 displayed increased resistance to the wild-type strain of S. sclerotiorum, but not to the SsXyl2-deletion strain. Hence, SsXyl2 acts as a CDIP that manipulates host cell physiology by interacting with hypersensitive induced reaction protein to facilitate colonization by S. sclerotiorum. These findings provide valuable insights into the pathogenic mechanisms of CDIPs in necrotrophic pathogens and lead to a more promising approach for breeding resistant crops against S. sclerotiorum.

Temporal Profiling of Host Proteome against Different M. tuberculosis Strains Reveals Delayed Epigenetic Orchestration.

Apart from being preventable and treatable, tuberculosis is the deadliest bacterial disease afflicting humankind owing to its ability to evade host defence responses, many of which are controlled by epigenetic mechanisms. Here, we report the temporal dynamics of the proteome of macrophage-like host cells after infecting them for 6, 18, 30, and 42 h with two laboratory strains (H37Ra and H37Rv) and two clinical strains (BND433 and JAL2287) of Mycobacterium tuberculosis (MTB). Using SWATH-MS, the proteins characterized at the onset of infection broadly represented oxidative stress and cell cytoskeleton processes. Intermediary and later stages of infection are accompanied by a reshaping of the combination of proteins implicated in histone stability, gene expression, and protein trafficking. This study provides strain-specific and time-specific variations in the proteome of the host, which might further the development of host-directed therapeutics and diagnostic tools against the pathogen. Also, our findings accentuate the importance of proteomic tools in delineating the complex recalibration of the host defence enabled as an effect of MTB infection. To the best of our knowledge, this is the first comprehensive proteomic account of the host response to avirulent and virulent strains of MTB at different time periods of the life span of macrophage-like cells. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE repository with the dataset identifier PXD022352.

SARS-CoV-2-infected hiPSC-derived cardiomyocytes reveal dynamic changes in the COVID-19 hearts

BackgroundThe ongoing coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on our societies. Moreover, the disease’s extensive and sustained symptoms are now becoming a nonnegligible medical challenge. In this respect, data indicate that heart failure is one of the most common readmission diagnoses among COVID-19 patients.MethodsIn this study, we used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes to develop an in vitro model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and studied the dynamic changes occurring in cardiomyocytes after SARS-CoV-2 infection.ResultsTo this end, we have created an effective time series SARS-CoV-2 infection model exhibiting different functional patterns of up- and downregulated proteins, and demonstrating that SARS-CoV-2 mainly affects (i) the lipid and the energy metabolism of hiPSC-derived cardiomyocytes during the early infection stage, and (ii) the DNA repair ability of cardiomyocytes during the late infection stage. By analyzing the proteome changes occurring at different infection timepoints, we were able to observe that the simulated disease (COVID-19) course developed rapidly, and that each of the studied timepoints was characterized by a distinct protein expression pattern.ConclusionsOur findings highlight the importance of early detection and personalized treatment based on the disease stage. Finally, by combing the proteomics data with virus-host interaction network analysis, we were able to identify several potential drug targets for the disease.

Transcriptional insights of citrus defense response against Diaporthe citri

Citrus melanose, caused by Diaporthe citri, is one of the most important and widespread fungal diseases of citrus. Previous studies demonstrated that the citrus host was able to trigger the defense response to restrict the spread of D. citri. However, the molecular mechanism underlying this defense response has yet to be elucidated. Here, we used RNA-Seq to explore the gene expression pattern at the early (3 days post infection, dpi) and late (14 dpi) infection stages of citrus leaves in response to D. citri infection, and outlined the differences in transcriptional regulation associated with defense responses. The functional enrichment analysis indicated that the plant cell wall biogenesis was significantly induced at the early infection stage, while the callose deposition response was more active at the late infection stage. CYP83B1 genes of the cytochrome P450 family were extensively induced in the callus deposition-mediated defense response. Remarkably, the gene encoding pectin methylesterase showed the highest upregulation and was only found to be differentially expressed at the late infection stage. Genes involved in the synthesis and regulation of phytoalexin coumarin were effectively activated. F6’H1 and S8H, encoding key enzymes in the biosynthesis of coumarins and their derivatives, were more strongly expressed at the late infection stage than at the early infection stage. Collectively, our study profiled the response pattern of citrus leaves against D. citri infection and provided the transcriptional evidence to support the defense mechanism.

Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni?

CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology. We invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5-94% and 66.4-85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W. The novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of nanotechnology-based immunotherapy, not only for schistosomiasis, but also for other parasitic infections in which chemotherapy has been shown to be immune-dependent. The results propose that the immunodominant reactivity of the anti-SmI serum, Schistosoma mansoni fructose biphosphate aldolase, SmFBPA, merits serious attention as a therapeutic and vaccine candidate.

Altered Gene Expression of the Parasitoid Pteromalus puparum after Entomopathogenic Fungus Beauveria bassiana Infection

Both parasitoids and entomopathogenic fungi are becoming increasingly crucial for managing pest populations. Therefore, it is essential to carefully consider the potential impact of entomopathogenic fungi on parasitoids due to their widespread pathogenicity and the possible overlap between these biological control tools during field applications. However, despite their importance, little research has been conducted on the pathogenicity of entomopathogenic fungi on parasitoids. In our study, we aimed to address this knowledge gap by investigating the interaction between the well-known entomopathogenic fungus Beauveria bassiana, and the pupal endoparasitoid Pteromalus puparum. Our results demonstrated that the presence of B. bassiana significantly affected the survival rates of P. puparum under laboratory conditions. The pathogenicity of B. bassiana on P. puparum was dose- and time-dependent, as determined via through surface spraying or oral ingestion. RNA-Seq analysis revealed that the immune system plays a primary and crucial role in defending against B. bassiana. Notably, several upregulated differentially expressed genes (DEGs) involved in the Toll and IMD pathways, which are key components of the insect immune system, and antimicrobial peptides were rapidly induced during both the early and late stages of infection. In contrast, a majority of genes involved in the activation of prophenoloxidase and antioxidant mechanisms were downregulated. Additionally, we identified downregulated DEGs related to cuticle formation, olfactory mechanisms, and detoxification processes. In summary, our study provides valuable insights into the interactions between P. puparum and B. bassiana, shedding light on the changes in gene expression during fungal infection. These findings have significant implications for the development of more effective and sustainable strategies for pest management in agriculture.

The Performance of Diagnostic Tests for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the South African Population: A Scoping Review.

To determine the performance and reliability of diagnostic tests for the identification of SARS-CoV-2 infection in South Africa, we conducted a scoping review to identify published studies undertaken in the English language from March 2020 to August 2022 that evaluated the performance of antigen- and antibody-based diagnostic tests for SARS-CoV-2 in South Africa. We identified 17 relevant peer-reviewed articles; six reported on SARS-CoV-2 gene and/or antigen detection whilst 11 reported on antibody detection. Of the SARS-CoV-2 gene and/or antigen-based tests, sensitivity ranged from 40% to 100%, whilst for the antibody-based tests, sensitivity ranged from 13% to 100%. All tests evaluated were highly dependent on the stage of infection and the timing of sample collection. This scoping review demonstrated that no single SARS-CoV-2 gene and/or antigen- or antibody-based assay was sufficiently sensitive and specific simultaneously. The sensitivity of the tests was highly dependent on the timing of sample collection with respect to SARS-CoV-2 infection. In the case of SARS-CoV-2 gene and/or antigen detection, the earlier the collection of samples, the greater the sensitivity, while antibody detection tests showed better sensitivity using samples from later stages of infection.

A major facilitator superfamily transporter PlMFS1 contributes to growth, oosporogenesis, and pathogenesis of Peronophythora litchii

Major facilitator superfamily (MFS) transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism. Peronophythora litchii causes the most destructive disease on lichi, litchi downy blight. PlM90 was reported as a key oosporogenesis regulator. Here, we identified an MFS transporter gene PlMFS1, which is up-regulated during oospore formation at the late infection stage, while down-regulated in the PlM90 mutant. To investigate PlMFS1 function, we generated PlMFS1 knockout mutants using CRISPR/Cas9-mediated genome editing technology. Compared with the wild-type strain SHS3, PlMFS1 deletion impaired mycelium growth, zoospore release, oospore production and pathogenicity. Furthermore, PlMFS1 deletion significantly affected P. litchii utilization of fructose, lactose and maltose, and may be the PlMFS1 mechanism involved in mycelial growth. PlMFS1 gene deletion also led to deceased laccase activity, laccase-encoding gene downregulation and impaired P. litchii pathogenicity. To our knowledge, this is the first report of an MFS transporter involved in sugar utilization, sexual reproduction, asexual reproduction and pathogenesis in oomycetes.

Emerging role of cyclophilin A in HIV-1 infection: from producer cell to the target cell nucleus.

The HIV-1 genome encodes a small number of proteins with structural, enzymatic, regulatory, and accessory functions. These viral proteins interact with a number of host factors to promote the early and late stages of HIV-1 infection. During the early stages of infection, interactions between the viral proteins and host factors enable HIV-1 to enter the target cell, traverse the cytosol, dock at the nuclear pore, gain access to the nucleus, and integrate into the host genome. Similarly, the viral proteins recruit another set of host factors during the late stages of infection to orchestrate HIV-1 transcription, translation, assembly, and release of progeny virions. Among the host factors implicated in HIV-1 infection, Cyclophilin A (CypA) was identified as the first host factor to be packaged within HIV-1 particles. It is now well established that CypA promotes HIV-1 infection by directly binding to the viral capsid. Mechanistic models to pinpoint CypA's role have spanned from an effect in the producer cell to the early steps of infection in the target cell. In this review, we will describe our understanding of the role(s) of CypA in HIV-1 infection, highlight the current knowledge gaps, and discuss the potential role of this host factor in the post-nuclear entry steps of HIV-1 infection.

Risk factors and adverse drug reactions in HIV/AIDS patients at Undata Regional Hospital in Palu City, Indonesia

AIDS (acquired immunodeficiency syndrome) is a clinical manifestation of the late stage of HIV infection (human immunodeficiency virus). This virus attacks CD4 cells in the immune system which is an important component in fighting infection. Without treatment, HIV can gradually destroy the immune system and lead to AIDS. This study aims to identify risk factors and determine and identify the type of ADR in HIV/AIDS patients at Undata Regional General Hospital Palu, Central Sulawesi province. This study used a cross-sectional observation method with prospective data collection, with a sample of 126 patients. Based on the results of the study, patients with HIV/AIDS had the most risk factors, namely homosexuality as many as 73 patients (58%), at the clinical stage, namely stage 3, 50 patients (39%), on opportunistic infection data, namely candidiasis, 35 patients (33%), and the initial CD4 cell count of <200 cells/mm3 in 27 patients (21%). Patients with HIV/AIDS who experienced ADR using antiretroviral drugs were 255 out of a total of 126 patients. Types of ADR that occur in HIV/AIDS patients include fever (6%), dizziness (47%), nausea (12%), vomiting (7%), insomnia (15%), easy hunger (1%), Hb low (1%), weakness (1%), rash (9%), headache (1%). Overall, these findings contribute valuable information for developing targeted interventions and improving the overall care and outcomes for individuals with HIV/AIDS.