Viral Lesions Research Articles

A retrospective analysis of oral tumors in dogs in Switzerland identifies peripheral odontogenic fibroma and melanoma as the predominant tumor types.

Determine the prevalence, types, and geographical distribution of oral tumors in dogs in Switzerland to provide insights into demographics, tumor characteristics, and trends. The medical and pathology records of dogs diagnosed with oral tumors from 2012 to 2022 were sourced from diagnostic laboratories in Switzerland. The focus was on histopathologically confirmed oral neoplasms. Inflammatory, viral, and cystic lesions were excluded. Geographic trends were analyzed by use of postal addresses, revealing local distributions. Of the 948 reports, 773 cases fulfilled the study's criteria. Benign tumors constituted 63% (487 of 773), with peripheral odontogenic fibroma being the most common (77.8% [379 of 487]). Among the malignant tumors, malignant melanoma was the most frequent (38.1% [109 of 286]), followed by squamous cell carcinoma (21% [60 of 286]) and fibrosarcoma (8% [23 of 286]). The locations of tumors varied, with a higher prevalence of malignant melanoma on the lips. Histopathologic findings indicated ulceration and necrosis were more common in malignant tumors. Significant differences were noted in the mitotic index between benign and malignant groups. No tumor predisposition was noted for any breed. Oral tumors were prevalent in older dogs (median age, 9.4 years). The findings highlighted the predominance of benign tumors in dogs in Switzerland, with specific histopathologic features distinguishing benign from malignant cases. Understanding the prevalence, types, and geographic distribution of oral tumors based on the representation in dogs in Switzerland may aid in early detection, appropriate diagnostic workup, and informed treatment planning for oral tumors in dogs.

Dual-lock-and-key virus-mimicking nanoprobes for ultra-high accurate and sensitive imaging of viral infections in vivo

Fluorescence in situ imaging of viral infection lesions in vivo is crucial for precise diagnosis of viral diseases and evaluation of the extent of viral infection. Nevertheless, achieving highly specific and sensitive fluorescence imaging of viral infection sites in vivo has posed a persistent challenge. Here, we developed a dual-lock-and-key virus-mimicking nanoprobe that consisted of polyamide dendrimers (PAMAM) loaded internally with molecular beacons double-triggered by apurinic/apyrimidinic nucleic acid endonuclease 1 (APE1) and viral RNA (vRNA), and surface-modified with the E protein of Japanese encephalitis virus (JEV). This activatable nanoprobe generated dramatically amplified fluorescent signals stimulated by expressed vRNA and APE1 during viral infection, enabling ultrahigh specific and sensitive imaging of the lesions of JEV infection in vivo. This study provides a potential approach for accurate and sensitive detection of viral infection levels and assessment of the efficacy of antiviral drugs in vivo.

Study on the activity and mechanism of herbal formula anti-infection powder (AIP) against influenza-virus-induced pneumonia through genetic susceptibility genes

Anti-infection powder (AIP), a patented Chinese herbal formulation, is used traditionally in the treatment of upper respiratory tract infections. In this study, an ethanol extract of AIP was demonstrated to inhibit influenza A virus (IAV) infection and IAV-induced pneumonia (IVP), both in vitro and in vivo, highlighting its potential mechanism of action. To determine the anti-IAV activity of AIP and to explore the possible mechanisms of inhibiting IAV-induced pneumonia. An ethanol extract was extracted from AIP and its major ingredients were determined by high-performance liquid chromatography (HPLC). An IAV-infected A549 cell model and an IAV-induced mouse pneumonia model were established to evaluate the therapeutic effects of AIP on IVP in vivo and in vitro. The mice were respectively administered AIP at high- and low-dose in different groups. The anti-IAV activity of AIP was evaluated by detecting viral load, lung lesion, lung index, suvival time, inflammatory cytokines and transcriptomic analysis in the lung tissue. The potential pathways and targets that involved in AIP against IVP were predicted by network pharmacology. Mendelian randomization (MR), colocalization analysis, and molecular docking were employed to identify novel therapeutic targets for IVP. Polymerase chain reaction (PCR) and Western blot (WB) techniques were used to confirm the effect of AIP on the expression of risk target genes in the lungs of IVP mice. In A549 cell line, AIP effectively inhibited IAV infection with IC50 values of 65.49 μg/mL. The anti-IAV activity of AIP was mainly determined by chlorogenic acid, forsythiarin, puerarin, paeoniflorin and prim-o-glucosylcimigin. Moreover, AIP inhibited the neuraminidase activity and the M gene expression in vitro. In vivo, oral administration of AIP significantly reduced viral load and improved lung tissue lesions. AIP decreased the concentration of pro-inflammatory factors such as IL-1β, TNF-α, and IFN-γ, and significantly increased the concentration of the anti-inflammatory factor IL-4. According to network pharmacology analysis, toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway may be the possible mechanisms by which AIP inhibits IVP and regulates excessive inflammatory response.Two new genes, LRG1 and PSMA4, associated with genetic susceptibility to influenza and pneumonia, predicted as potential IVP drug target genes by MR and colocalization analysis. The antiviral mechanism of AIP may be to inhibit the expression levels of LRG1 and PSMA4 in lungs of mouse IVP. AIP exhibited anti-IAV activities both in vitro and in vivo. AIP had a protective effect against pneumonia caused by influenza virus and can inhibit the progression of inflammation. This effect may be associated with its ability to inhibit the expression levels of genetic susceptibility genes (LRG1 and PSMA4) in lungs of mouse IVP. The findings of this study enhance our understanding of the role and mechanisms of AIP in the treatment of IVP.

Perinatal HIV infection and opportunistic infectious pathology: morphological features of the placenta

Opportunistic infections account for more than 90% of all deaths associated with immunosuppression resulting from exposure to the human immunodeficiency virus (HIV). Fatal opportunistic infections include Pneumocystis pneumonia, cryptococcosis, cytomegalovirus infection, and viral hepatitis B and/or C. HIV-infected pregnant women have a high incidence of cytomegalovirus infection, which increases the risk of transplacental transmission of HIV from mother to fetus. In addition, an important factor in perinatal transmission of HIV is a genital infection caused by herpes simplex virus type 2 detected during pregnancy in HIV-infected women. Also, at present, there is no doubt about the possibility of damage to placental cells by the SARS-CoV-2 virus and its transplacental transmission.The aim of this study was to study the morphological features of the placenta in the presence of opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV2 in HIV-infected pregnant women.Materials and methods. A study was conducted of 21 placentas with various pregnancy outcomes in HIV-infected women, including 12 placentas obtained as a result of term birth, 1 placenta from premature birth at 29 weeks, and 8 observations of failed miscarriages (non-developing pregnancy).Results and discussion. Viral lesions were represented by the action of HIV with giant cell metamorphosis of trophoblast cells and placental macrophages, as well as infiltration by immunocompetent cells and fibrosis of the villous stroma. In addition, groups of immature villi were identified, the edematous stroma of which contained an increased number of large cells with light nuclei. In HIV-infected pregnant women with immunosuppression, the outcome of pregnancy in 8 cases was a miscarriage with a morphologically detected and immunohistochemically confirmed infection caused by herpes simplex virus types 1/2 (3 observations), cytomegalovirus (2 observations), and SARS-CoV-2 (3 observations), in 1 case the outcome of pregnancy was premature birth with morphologically identified and immunohistochemically confirmed infection caused by the Epstein-Barr virus.Conclusion. The placentas of HIV-infected pregnant women are characterized by impaired villous maturation with stromal fibrosis, which is the morphological substrate of chronic placental insufficiency with varying degrees of compensation. If HIVinfected pregnant women have opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV-2, pronounced involutive-dystrophic changes are observed in the placentas — perivillous deposition fibrinoid, petrification, which increases the likelihood of an unfavorable pregnancy outcome in the form of miscarriage or premature birth.

Challenges in clinical diagnosis of Clade I Mpox: Highlighting the need for enhanced diagnostic approaches.

Due to limited diagnostic capacity and availability of point-of-care tests, diagnosis of Clade I mpox in the geographical regions most affected is usually on clinical grounds. This may be complicated due to the similarity between mpox and varicella (chickenpox) lesions. Visual assessment of lesions is also used for determining clinical progress and to assess patient outcomes in clinical trials. However, there has been no investigation into whether clinicians can (i) identify Clade I mpox compared to other viral lesions (ii) differentiate between Clade I mpox lesion stages. The objective of this study was to evaluate inter-rater reliability and agreement between clinicians assessing lesions in patients with Clade I mpox. We presented experienced clinicians with 17 images of Clade I mpox or varicella and asked them to independently indicate the most likely diagnosis-mpox or varicella-and to categorise the lesions according to their stage. When selecting the most likely diagnosis, accuracy varied across all images, the inter-rater reliability was poor (κ = 0.223; z = 10.1) and agreement was moderate (Po = 68%). When categorising lesions according to their type, if a single lesion type was present in the image, inter-rater reliability was moderate (κ = 0.671, z = 40.6) and agreement was good (Po = 78%), but when multiple lesion types were shown in an image, both inter-rater reliability (κ = 0.153, z = 10.5) and agreement (Po = 29%) decreased substantially. This study demonstrates that there are presently limitations in using visual assessment to diagnose Clade I mpox and evaluate lesion stage and treatment outcomes, which have an impact on clinical practice, public health and clinical trials. More robust indicators and tools are required to inform clinical, public-health, and research priorities, but these must be implementable in countries affected by mpox.

Mice with type I interferon signaling deficiency are prone to epilepsy upon HSV-1 infection

Viral encephalitis continues to be a significant public health concern. In our previous study, we discovered a lower expression of antiviral factors, such as IFN-β, STING and IFI16, in the brain tissues of patients with Rasmussen's encephalitis (RE), a rare chronic neurological disorder often occurred in children, characterized by unihemispheric brain atrophy. Furthermore, a higher cumulative viral score of human herpes viruses (HHVs) was also found to have a significant positive correlation with the unihemispheric atrophy in RE. Type I IFNs (IFN-I) signaling is essential for innate anti-infection response by binding to IFN-α/β receptor (IFNAR). In this study, we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1 (HSV-1) via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions. While all mice exhibited typical viral encephalitis lesions in their brains, HSV-induced epilepsy was only observed in A6 mice. The gene expression matrix, functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy. Additionally, ten key genes with the highest scores were identified. Taken together, these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions, thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.

A Mixture of T-Cell Epitope Peptides Derived from Human Respiratory Syncytial Virus F Protein Conferred Protection in DR1-TCR Tg Mice.

Human respiratory syncytial virus (HRSV) poses a significant disease burden on global health. To date, two vaccines that primarily induce humoral immunity to prevent HRSV infection have been approved, whereas vaccines that primarily induce T-cell immunity have not yet been well-represented. To address this gap, 25 predicted T-cell epitope peptides derived from the HRSV fusion protein with high human leukocyte antigen (HLA) binding potential were synthesized, and their ability to be recognized by PBMC from previously infected HRSV cases was assessed using an ELISpot assay. Finally, nine T-cell epitope peptides were selected, each of which was recognized by at least 20% of different donors' PBMC as potential vaccine candidates to prevent HRSV infection. The protective efficacy of F-9PV, a combination of nine peptides along with CpG-ODN and aluminum phosphate (Al) adjuvants, was validated in both HLA-humanized mice (DR1-TCR transgenic mice, Tg mice) and wild-type (WT) mice. The results show that F-9PV significantly enhanced protection against viral challenge as evidenced by reductions in viral load and pathological lesions in mice lungs. In addition, F-9PV elicits robust Th1-biased response, thereby mitigating the potential safety risk of Th2-induced respiratory disease during HRSV infection. Compared to WT mice, the F-9PV mice exhibited superior protection and immunogenicity in Tg mice, underscoring the specificity for human HLA. Overall, our results demonstrate that T-cell epitope peptides provide protection against HRSV infection in animal models even in the absence of neutralizing antibodies, indicating the feasibility of developing an HRSV T-cell epitope peptide-based vaccine.

Results of the study of the influence of viral liver damage in white rats under experimental conditions on liver tissue (trichrome Masson and immunohistochemistry marker cd68)

This article is supposed to determine the level of activity of viral (including SARS-CoV-2) damage to the liver tissue and the stage of liver fibrosis resulting from experimental viral damage to the liver. A viral lesion (including SARS-CoV-2) was also detected in the liver tissue, as a result of which the expression of the CD 68 marker in the liver tissue of normal and experimentally infected liver tissue was determined.

MVA-based vaccine candidates expressing SARS-CoV-2 prefusion-stabilized spike proteins of the Wuhan, Beta or Omicron BA.1 variants protect transgenic K18-hACE2 mice against Omicron infection and elicit robust and broad specific humoral and cellular immune responses.

Despite the decrease in mortality and morbidity due to SARS-CoV-2 infection, the incidence of infections due to Omicron subvariants of SARS-CoV-2 remains high. The mutations acquired by these subvariants, mainly concentrated in the receptor-binding domain (RBD), have caused a shift in infectivity and transmissibility, leading to a loss of effectiveness of the first authorized COVID-19 vaccines, among other reasons, by neutralizing antibody evasion. Hence, the generation of new vaccine candidates adapted to Omicron subvariants is of special interest in an effort to overcome this immune evasion. Here, an optimized COVID-19 vaccine candidate, termed MVA-S(3P_BA.1), was developed using a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein from the Omicron BA.1 variant. The immunogenicity and efficacy induced by MVA-S(3P_BA.1) were evaluated in mice in a head-to-head comparison with the previously generated vaccine candidates MVA-S(3P) and MVA-S(3Pbeta), which express prefusion-stabilized S proteins from Wuhan strain and Beta variant, respectively, and with a bivalent vaccine candidate composed of a combination of MVA-S(3P) and MVA-S(3P_BA.1). The results showed that all four vaccine candidates elicited, after a single intramuscular dose, protection of transgenic K18-hACE2 mice challenged with SARS-CoV-2 Omicron BA.1, reducing viral loads, histopathological lesions, and levels of proinflammatory cytokines in the lungs. They also elicited anti-S IgG and neutralizing antibodies against various Omicron subvariants, with MVA-S(3P_BA.1) and the bivalent vaccine candidate inducing higher titers. Additionally, an intranasal immunization in C57BL/6 mice with all four vaccine candidates induced systemic and mucosal S-specific CD4+ and CD8+ T-cell and humoral immune responses, and the bivalent vaccine candidate induced broader immune responses, eliciting antibodies against the ancestral Wuhan strain and different Omicron subvariants. These results highlight the use of MVA as a potent and adaptable vaccine vector against new emerging SARS-CoV-2 variants, as well as the promising feature of combining multivalent MVA vaccine candidates.

Heterogeneous encoding of temporal stimuli in the cerebellar cortex

Local feedforward and recurrent connectivity are rife in the frontal areas of the cerebral cortex, which gives rise to rich heterogeneous dynamics observed in such areas. Recently, similar local connectivity motifs have been discovered among Purkinje and molecular layer interneurons of the cerebellar cortex, however, task-related activity in these neurons has often been associated with relatively simple facilitation and suppression dynamics. Here, we show that the rodent cerebellar cortex supports heterogeneity in task-related neuronal activity at a scale similar to the cerebral cortex. We provide a computational model that inculcates recent anatomical insights into local microcircuit motifs to show the putative basis for such heterogeneity. We also use cell-type specific chronic viral lesions to establish the involvement of cerebellar lobules in associative learning behaviors. Functional heterogeneity in neuronal profiles may not merely be the remit of the associative cerebral cortex, similar principles may be at play in subcortical areas, even those with seemingly crystalline and homogenous cytoarchitectures like the cerebellum.

Duck Tembusu virus induces incomplete autophagy via the ERK/mTOR and AMPK/mTOR signalling pathways to promote viral replication in neuronal cells

Duck Tembusu virus (DTMUV) is a neurotropic virus in the genus Flavivirus that causes massive economic losses to the poultry industry in China and neighbouring countries. Autophagy is pivotal in cellular responses to pathogens and in viral pathogenesis. However, little is known about the roles of autophagy in DTMUV replication and viral pathogenesis, especially in neuropathogenesis. In this study, mouse neuroblastoma cells (Neuro-2a) were used to establish a cell model of DTMUV infection. Our experiments indicated that DTMUV infection induced incomplete autophagy in Neuro-2a cells. Then, we used different autophagy regulators to alter the autophagy induced by DTMUV and found that incomplete autophagy promoted DTMUV replication. Furthermore, we showed that DTMUV infection activated the ERK and AMPK pathways, resulting in decreased phosphorylation of the autophagy repressor mTOR, subsequently leading to autophagic induction. In addition, we utilized ICR mice in an animal model of DTMUV infection to evaluate the autophagic responses in brain tissues and investigate the effects of autophagy on viral replication and tissue lesions. Our results confirmed that DTMUV induced incomplete autophagy in mouse brain tissues and that autophagy inducer treatment promoted DTMUV replication and aggravated DTMUV-induced lesions, whereas autophagy inhibitor treatment had the opposite effects. In summary, DTMUV infection induced incomplete autophagy through the ERK/mTOR and AMPK/mTOR signalling pathways to promote viral replication in mouse neuronal cells, and DTMUV-induced incomplete autophagy contributed to the neuropathogenesis of DTMUV.

Ultrasound and Doppler Diagnostic Capabilities of Lymph Nodes in Thyroid Cancer

nodular lesions, autoimmune thyroiditis and neoplastic processes are the leading diseases of the thyroid gland (TG), when it is characterized by the cervical lymph nodes (LN) enlargement. They can undergo macro- and microscopic changes due to inflammatory processes of bacterial or viral origin, benign and malignant lesions of the neck, head and mediastinum. Doppler ultrasonography (US) plays a significant role among the new methods of screening for altered LN and differential diagnosis of pathological processes. The aim of this work is to determine the prospects for the use of LN lesions’ ultrasound diagnostics in inflammatory and oncological processes of the TG. Ultrasound diagnostics was performed to determine Doppler signs (EDV, PSV, RI) and changes in neck LN in 175 patients with and without TG pathologies. According to the results of histopathology, the patients were divided into 4 groups: 46 healthy patients without any thyroid pathology, 44 patients with inflammatory thyroid diseases, 42 patients with thyroid cancer but without metastatic LN involvement, 43 patients with metastatic LN involvement – Thyroid cancer. B-mode ultrasound diagnostic data demonstrated positive complementation with echostructural signs and changes in vascularization. It manifested in a wide range of velocities and atypical angioarchitectonics. 13 (31%) patients had increased vascularization with PSV – 23-45 cm/s, EDV – 14- 8 cm/s, RI – 0.32-0.46. It shows the progression of proliferative processes without necrotic changes in the hilus and its periphery. In 18 (43%) patients dynamic Doppler observation indicated the appearance of accelerated blood flow and an atypical vascular concentration outside nodular capsules. It is an indicator of the cancer spread. Color Doppler mapping and energy Doppler coding of cervical metastases are important diagnostic techniques, that qualitatively and quantitatively complements and details B-mode ultrasound diagnosis.

Developing and Testing Deep Learning Models for Monkeypox and Herpes Zoster Rash Differentiation

Monkeypox (mpox) is a viral infection known for its pimple-like skin rashes found across the body. Since the 2022 outbreak, monkeypox has been mistaken for similar conditions, such as herpes zoster (shingles). In the past, deep learning, a form of machine learning in which software models learn to form conclusions using artificial neural networks (ANNs) similar to that of the human brain, have been utilized to identify various dermatological conditions. Utilizing the engineering method, the following research question was inquired: How can deep learning be applied to a mobile application to distinguish monkeypox viral lesions from herpes zoster viral lesions? ResNet50 and MobileNetV3, two deep-learning models, were trained utilizing transfer learning for the task of differentiating between monkeypox and shingles. ResNet50 and MobileNetV3 were then tested utilizing a separate testing set of images. Both models achieved an accuracy of 93.10 percent, with ResNet50 achieving a loss of 17.03 percent and MobileNetV3 achieving a loss of 29.30 percent. It was concluded that ResNet50 may be more precise due to its lower loss percentage, indicating fewer instances of errors. An end-user prototype of a mobile application was created to simulate these deep-learning models. These findings suggest that deep learning is an efficient and precise solution to prevent the misdiagnosis of monkeypox, potentially hindering the rising cases of this virus while aiding in proactive measures to identify and treat monkeypox victims. 

Controlling viral inflammatory lesions by rebalancing immune response patterns.

In this review, we discuss a variety of immune modulating approaches that could be used to counteract tissue-damaging viral immunoinflammatory lesions which typify many chronic viral infections. We make the point that in several viral infections the lesions can be largely the result of one or more aspects of the host response mediating the cell and tissue damage rather than the virus itself being directly responsible. However, within the reactive inflammatory lesions along with the pro-inflammatory participants there are also other aspects of the host response that may be acting to constrain the activity of the damaging components and are contributing to resolution. This scenario should provide the prospect of rebalancing the contributions of different host responses and hence diminish or even fully control the virus-induced lesions. We identify several aspects of the host reactions that influence the pattern of immune responsiveness and describe approaches that have been used successfully, mainly in model systems, to modulate the activity of damaging participants and which has led to lesion control. We emphasize examples where such therapies are, or could be, translated for practical use in the clinic to control inflammatory lesions caused by viral infections.

Experimental study of the effectiveness of ademethionine and inosine glycyl-cysteinyl-glutamate disodium in the treatment of dichloroethane-induced toxic hepatitis

Introduction. Currently, in the search for drugs for the toxic liver damage treatment, considerable attention is paid to glutathione preparations and its metabolic precursors. There are separate reports in the literature on the hepatoprotective and antifibrotic effects of glutathione disulfide in viral liver lesions, which gives grounds for their additional study when exposed to hepatotropic substances.
 Material and methods. Performing a comparative assessment of the hepatoprotective effect of inosine glycyl-cysteinyl-glutamate disodium and ademetionine on the model of dichloroethane-induced toxic hepatitis in rats was carried out with the formation of the following experimental groups of animals: no treatment; with the introduction of physiological saline; with the introduction of inosine glycyl-cysteinyl-glutamate disodium; with the introduction of ademetionine, as well as a group of intact animals. The study drugs were administered intraperitoneally for 10 days. In the course of the study, biochemical indicators of cytolytic and cholestatic syndromes of liver damage were determined, the activity of its detoxification system and plastic function were assessed.
 Results. In groups that did not receive treatment, but received physiological saline, the lethality of experimental animals by the 20th day of observation was 40%, in the group treated with ademetionine – 
 10%. In the group treated with inosine glycyl-cysteinyl-glutamate disodium, no death of animals was observed. The use of inosine glycyl-cysteinyl-glutamate disodium led to a more significant decrease in the indicators of cytolytic and cholestatic syndromes, as well as normalization of the functional activity of the liver (restoration of the content of glutathione in the liver tissue) and its plastic function (restoration 
 of the level of total blood serum protein and glycogen content in the liver parenchyma) to a greater extent than with ademetionine.
 limitation. The experimental study was carried out on outbred male rats weighing 180–220 g, kept under standard vivarium conditions in one cage, no more than 6 individuals, divided into groups by randomization with the exclusion of weakened and sick animals from the study.
 Conclusion. The study provided an experimental justification for further study of the hepatoprotective effect of inosine glycylcysteinylglutamate disodium in toxic liver damage.

Ozonated sunflower oil in wound healing in a cat: Case report

Therapies with the use of ozone have been increasingly applied in both human and veterinary medicine due to its high oxygenating and antioxidant power. These factors stimulate the formation of deoxygenating substances within pathogens, which release oxygen into oxyhemoglobins, increasing its migration to epithelial tissues, thus being used in fungal, bacterial, viral and skin lesions. This work aims to report a clinical case of a feline whose veterinary medical clinic’s routine utilized ozone therapy in the primary treatment via ozonized sunflower oil in the tissue repair process. This method can help with the dermal secondary intention healing, having a good acceptance, not causing discomfort or stress to the animal and contributing to its well-being.

Immunization of pigs with replication-incompetent adenovirus-vectored African swine fever virus multi-antigens induced humoral immune responses but no protection following contact challenge.

African swine fever virus (ASFV) is a pathogen of great economic importance given that continues to threaten the pork industry worldwide, but there is no safe vaccine or treatment available. Development of a vaccine is feasible as immunization of pigs with some live attenuated ASFV vaccine candidates can confer protection, but safety concerns and virus scalability are challenges that must to be addressed. Identification of protective ASFV antigens is needed to inform the development of efficacious subunit vaccines. In this study, replication-incompetent adenovirus-vectored multicistronic ASFV antigen expression constructs that covered nearly 100% of the ASFV proteome were generated and validated using ASFV convalescent serum. Swine were immunized with a cocktail of the expression constructs, designated Ad5-ASFV, alone or formulated with either Montanide ISA-201™ (ASFV-ISA-201) or BioMize® adjuvant (ASFV-BioMize). These constructs primed strong B cell responses as judged by anti-pp62-specific IgG responses. Notably, the Ad5-ASFV and the Ad5-ASFV ISA-201, but not the Ad5-ASFV BioMize®, immunogens primed significantly (p < 0.0001) higher anti-pp62-specific IgG responses compared with Ad5-Luciferase formulated with Montanide ISA-201™ adjuvant (Luc-ISA-201). The anti-pp62-specific IgG responses underwent significant (p < 0.0001) recall in all the vaccinees after boosting and the induced antibodies strongly recognized ASFV (Georgia 2007/1)-infected primary swine cells. However, following challenge by contact spreaders, only one pig nearly immunized with the Ad5-ASFV cocktail survived. The survivor had no typical clinical symptoms, but had viral loads and lesions consistent with chronic ASF. Besides the limited sample size used, the outcome suggests that in vivo antigen expression, but not the antigen content, might be the limitation of this immunization approach as the replication-incompetent adenovirus does not amplify in vivo to effectively prime and expand protective immunity or directly mimic the gene transcription mechanisms of attenuated ASFV. Addressing the in vivo antigen delivery limitations may yield promising outcomes.

Lesions in the oral cavity during hospitalization due to COVID-19: a Systematic Review

Introduction: The Systematic Review aims to assess the prevalence of oral cavity lesions in adult patients diagnosed with COVID-19 hospitalized at the infirmary or ICU. Methodology: A search was carried out in 6 databases and in grey literature. The methodological quality was analyzed using the tools in the Joana Briggs Institute (JBI) manual. Results: A total of 3,952 studies were found, remaining 79 for full reading, and 24 studies were included (six case reports, four case series, three cohort studies, ten cross-sectional studies and one case control). All 24 studies reported the location and types of lesions, thus the decreasing prevalence of the types of lesions are candidiasis (20,30%), followed by nonspecific ulcerated lesions (11,42%), nonspecific oral bleeding (4.30%) and viral lesions (2.71%). The location of the lesions is described as lips, tongue, palate and gums. Conclusion: Patients hospitalized in a hospital environment develop lesions in the oral cavity, as well as patients diagnosed with COVID-19, with fungal lesions being the most prevalent both in hospital patients and in patients diagnosed with COVID-19.

Dermatologic toxicity of high doses of tiothepa in children. Case report

Hematopoietic stem cell transplantation (HSCT) is a treatment modality for a number of severe malignant and non-neoplastic diseases. Autologous hematopoietic stem cell transplantation (auto-HSCT) improves outcomes in patients with solid and hematological malignancies. Skin lesions at the auto-HSCT stage are quite common and represent an important diagnostic and therapeutic problem. The most significant causes of skin lesions in auto-HSCT are drug toxicity, infectious and viral lesions. Each of the complications can manifest itself to varying degrees as well as combine with others, having a significant negative on the patient’s condition, posing a threat to the patient’s life in severe cases.

Characteristics and Treatment of anti-NMDAR Encephalitis in People Living with HIV: A Case Report and Literature Review (P5-5.005)

<h3>Objective:</h3> To describe the risk factors, symptoms, treatment, and outcomes of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring in people living with HIV (PLWH). <h3>Background:</h3> Herpes simplex virus encephalitis is a known trigger of anti-NMDAR encephalitis. In recent years, multiple case reports also document anti-NMDAR encephalitis in PLWH, especially those who develop cerebrospinal fluid (CSF) escape, defined by an elevated CSF viral load in the setting of plasma viral suppression. Although the relationship between HIV and other viruses with anti-NMDAR encephalitis has not been fully elucidated, possible mechanisms include molecular mimicry or viral-induced release of NMDAR and other proteins as a result of neurotoxicity. HIV-induced functional dysregulation of CD4+ cell subtypes is another plausible contributor. <h3>Design/Methods:</h3> We conducted a literature search for published cases of autoimmune encephalitis in PLWH. We added an unpublished case from our center and described the clinical features of this unique cohort. <h3>Results:</h3> Eight published cases of anti-NMDAR encephalitis among PLWH were identified, as well as one unpublished case from our center. Common trends in these 9 cases include elevated CSF HIV viral load, T2 hyperintense lesions on MRI, and clinical improvement with immunomodulation. Our patient was a 51-year-old woman who presented off of antiretroviral therapy (recent CD4 range 199–252 cells/mm3) with status epilepticus and was found to have an elevated CSF HIV viral load and multiple non-enhancing T2-hyperintense lesions on brain MRI. Anti-NMDAR antibodies were positive in the serum and CSF. She did not respond to steroids or intravenous immunoglobulins, but began to improve after plasma exchange and was subsequently treated with rituximab. <h3>Conclusions:</h3> Anti-NMDAR encephalitis is an important, treatable consideration in PLWH who present with altered mental status or new seizures. Patients with an elevated CSF viral load may be at higher risk for this syndrome, and immunomodulation may be indicated even in patients who are immunosuppressed. <b>Disclosure:</b> Dr. White has nothing to disclose. Dr. Vila has nothing to disclose. The institution of Dr. Bissonnette has received research support from Michael J Fox Foundation. The institution of Dr. Bissonnette has received research support from Cogan Family Foundation. Dr. Martinez-Ramirez has nothing to disclose. Dr. Anand has nothing to disclose. Dr. Cervantes-Arslanian has nothing to disclose.