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Nature Communications Apr 2024Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we...
Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection.
Topics: CD47 Antigen; Humans; Staphylococcus aureus; Animals; Superinfection; Mice; Epithelial Cells; Staphylococcal Infections; Influenza, Human; Bacterial Adhesion; Respiratory Mucosa; Mice, Inbred C57BL; Bronchi; Bacterial Proteins; Orthomyxoviridae Infections; Mice, Knockout; Influenza A Virus, H1N1 Subtype
PubMed: 38693120
DOI: 10.1038/s41467-024-47963-5 -
Surgical Pathology Clinics Jun 2024The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia,... (Review)
Review
The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia, organizing pneumonia, and bronchiolitis. Lung injury was caused by primary viral injury, exaggerated immune responses, and superinfection with bacteria and fungi. Although fatality rates have decreased from the early phases of the pandemic, persistent pulmonary dysfunction occurs and its pathogenesis remains to be fully elucidated.
Topics: Humans; COVID-19; Lung; SARS-CoV-2; Lung Diseases
PubMed: 38692805
DOI: 10.1016/j.path.2023.11.006 -
BMJ Case Reports Apr 2024Varicella is the manifestation of primary infection with the varicella-zoster virus, mainly affecting preschool and school-aged children. The children suffer from a...
Varicella is the manifestation of primary infection with the varicella-zoster virus, mainly affecting preschool and school-aged children. The children suffer from a generalised, vesicular rash and fever. Despite the infection's typically non-threatening course, a variety of severe complications have been described.The authors present the case of a female infant suffering from varicella and developing preseptal cellulitis with a frontal abscess while being treated with intravenous antibiotics. Otorhinolaryngology consultation was sought since the clinical image was highly suggestive for sinusitis complications, namely orbital cellulitis and frontal bone osteomyelitis (Pott's puffy tumour). However, the child was below the age of frontal sinus development and there was no other apparent sign of sinonasal involvement. Ultrasonography revealed a mid-frontal collection without signs of abscess formation preseptally or postseptally, leading to the diagnosis of cutaneous superinfection of varicella lesions. The frontal abscess was drained, and the child fully recovered under antibiotic treatment.
Topics: Humans; Female; Infant; Chickenpox; Diagnosis, Differential; Anti-Bacterial Agents; Abscess; Sinusitis; Rhinitis; Acute Disease; Rhinosinusitis
PubMed: 38684354
DOI: 10.1136/bcr-2021-246379 -
Viruses Mar 2024Individuals chronically infected with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) present an increased risk of developing cirrhosis and hepatocellular...
Individuals chronically infected with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) present an increased risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV mono-infected individuals. Although HDV only replicates in individuals coinfected or superinfected with HBV, there is currently no in vitro model that can stably express both viruses simultaneously, mimicking the chronic infections seen in HBV/HDV patients. Here, we present the HepG2BD cell line as a novel in vitro culture system for long-term replication of HBV and HDV. HepG2BD cells derive from HepG2.2.15 cells in which a 2 kb HDV cDNA sequence was inserted into the adeno-associated virus safe harbor integration site 1 (AAVS1) using CRISPR-Cas9. A Tet-Off promoter was placed 5' of the genomic HDV sequence for reliable initiation/repression of viral replication and secretion. HBV and HDV replication were then thoroughly characterized. Of note, non-dividing cells adopt a hepatocyte-like morphology associated with an increased production of both HDV and HBV virions. Finally, HDV seems to negatively interfere with HBV in this model system. Altogether, HepG2BD cells will be instrumental to evaluate, in vitro, the fundamental HBV-HDV interplay during simultaneous chronic replication as well as for antivirals screening targeting both viruses.
Topics: Hepatitis Delta Virus; Humans; Virus Replication; Hepatitis B virus; Hep G2 Cells; Hepatocytes; Hepatitis D; CRISPR-Cas Systems; Dependovirus; Coinfection
PubMed: 38675875
DOI: 10.3390/v16040532 -
Viruses Mar 2024In the last few years, there has been a dramatic increase in the number of discovered viruses that are transmitted by arthropods. Some of them are pathogenic for humans...
In the last few years, there has been a dramatic increase in the number of discovered viruses that are transmitted by arthropods. Some of them are pathogenic for humans and mammals, and the pathogenic potential of others is unknown. The genus belongs to the family and includes arboviruses that cause severe human diseases with damage to the central nervous system and hemorrhagic fevers, as well as viruses with unknown vectors and viruses specific only to insects. The latter group includes Lammi virus, first isolated from a mosquito pool in Finland. It is known that Lammi virus successfully replicates in mosquito cell lines but not in mammalian cell cultures or mice. Lammi virus reduces the reproduction of West Nile virus during superinfection and thus has the potential to reduce the spread of West Nile virus in areas where Lammi virus is already circulating. In this work, we isolated Lammi virus from a pool of adult mosquitoes that hatched from larvae/pupae collected in Saint Petersburg, Russia. This fact may indicate transovarial transmission and trans-stadial survival of the virus.
Topics: Animals; Aedes; Russia; Female; Mosquito Vectors; Flaviviridae; Larva
PubMed: 38675870
DOI: 10.3390/v16040527 -
Die Anaesthesiologie Jun 2024Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease progression. Comorbidities, such as chronic arterial hypertension,...
BACKGROUND
Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease progression. Comorbidities, such as chronic arterial hypertension, diabetes mellitus, advanced maternal age and high body mass index, may predispose to severe disease. The management of pregnant COVID-19 patients on the intensive care unit (ICU) is challenging and requires careful consideration of maternal, fetal and ethical issues.
OBJECTIVE
Description and discussion of intensive care treatment strategies and perinatal anesthesiological management in patients with COVID-19 acute respiratory distress syndrome (CARDS).
MATERIAL AND METHODS
We analyzed the demographic data, maternal medical history, clinical intensive care management, complications, indications and management of extracorporeal membrane oxygenation (ECMO) and infant survival of all pregnant patients treated for severe CARDS in the anesthesiological ICU of a German university hospital between March and November 2021.
RESULTS
The cohort included 9 patients with a mean age of 30.3 years (range 26-40 years). The gestational age ranged from 21 + 3 weeks to 37 + 2 weeks. None of the patients had been vaccinated against SARS-CoV‑2. Of the nine patients seven were immigrants and communication was hampered by inadequate Central European language skills. Of the patients five had a PO/FO index < 150 mm Hg despite escalated invasive ventilation (FO > 0.9 and a positive end-expiratory pressure [PEEP] of 14 mbar) and were therefore treated with repeated prolonged prone positioning maneuvers (5-14 prone positions for 16 h each, a total of 47 prone positioning treatments) and 2 required treatment with inhaled nitric oxide and venovenous ECMO. The most common complications were bacterial superinfection of the lungs, urinary tract infection and delirium. All the women and five neonates survived. All newborns were delivered by cesarean section, two patients were discharged home with an intact pregnancy and two intrauterine fetal deaths were observed. None of the newborns tested positive for SARS-CoV‑2 at birth.
CONCLUSION
High survival rates are possible in pregnant patients with CARDS. The peripartum management of pregnant women with CARDS requires close interdisciplinary collaboration and should prioritize maternal survival in early pregnancy. In our experience, prolonged prone positioning, an essential evidence-based cornerstone in the treatment of ARDS, can also be safely used in advanced stages of pregnancy. Inhaled nitric oxide (iNO) and ECMO should be considered as life-saving treatment options for carefully selected patients. For cesarean section, neuraxial anesthesia can be safely performed in patients with mild CARDS if well planned but the therapeutic anticoagulation recommended for COVID-19 may increase the risk of bleeding complications, making general anesthesia a more viable alternative, especially in severe disease.
Topics: Humans; Female; Pregnancy; COVID-19; Pregnancy Complications, Infectious; Extracorporeal Membrane Oxygenation; Adult; Intensive Care Units; Infant, Newborn; Respiratory Distress Syndrome; Critical Care; Cesarean Section; Germany; Cohort Studies; Pregnancy Outcome
PubMed: 38671334
DOI: 10.1007/s00101-024-01405-5 -
Poultry Science Jun 2024Avian leukosis virus subgroup K (ALV-K) is composed of newly emerging isolates, which cluster separately from the well-characterized subgroups A, B, C, D, E, and J in...
Avian leukosis virus subgroup K (ALV-K) is composed of newly emerging isolates, which cluster separately from the well-characterized subgroups A, B, C, D, E, and J in sequence analysis, and exhibits a specific host range and a unique pattern of superinfection interference. Avian leukosis virus subgroup K replicate more slowly in avian cells than other ALV strains, leading to escaped detection during ALV eradication, but the underlying mechanism are largely unknown. In our previous study, we have reported that JS11C1 and most of other suspected ALV-K strains possessed unique mutations in the U3 region. Here, we selected 5 mutations in some important transcriptional regulation elements to explore the possible factor contributing for the lower activity of LTR, including CA-TG mutation in the CAAT box, 21 nt deletion in the CAAT box, A-G and A-T mutations in the CArG boxes, 11 nt insertion in the PRE boxes, and C-T mutation in the TATA box. On the basis of infectious clone of JS11C1, we demonstrated that the 11 nt fragment in the PRE boxes was associated with the transcription activity of LTR, the enhancer ability of U3, and the replication capacity of the virus. Notably, we determined the differential U3-protein interaction profile of ALVs and found that the 11 nt fragment specifically binds to cellular SERPINE1 mRNA binding protein 1 (SERBP1) to increase the LTR activity and enhance virus replication. Collectively, these findings reveal that a 11 nt fragment in the U3 gene contributed to its binding ability to the cellular SERBP1 to enhance its transcription and the infectious virus productions in avian cells. This study highlighted the vital role of host factor in retrovirus replication and thus provides a new perspective to elucidate the interaction between retrovirus and its host and a molecular basis to develop efficient strategies against retroviruses.
Topics: Avian Leukosis Virus; Animals; Avian Leukosis; Chickens; Poultry Diseases; Transcription, Genetic; RNA-Binding Proteins; Virus Replication; Cell Line; Mutation
PubMed: 38663206
DOI: 10.1016/j.psj.2024.103755 -
Open Forum Infectious Diseases Apr 2024Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression...
Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression despite tecovirimat treatment. Treatment resistance can be due to acquired mpox strain mutations, most often occurring in an immunocompromised host. We present the case of a male with AIDS who developed disseminated treatment-resistant mpox infection complicated by superimposed bacterial and fungal infections. His orthopoxvirus polymerase chain reaction result remained positive despite treatment with 4 weeks of oral tecovirimat and 3 doses of intravenous cidofovir. Poor response to antiviral therapy was likely due to his underlying immunocompromised state; however, strain resistance cannot be ruled out given that the patient had started but not completed a 14-day course of tecovirimat 8 months prior, at the time of initial mpox diagnosis. Patients with mpox who are immunocompromised may require extended and additional treatment beyond the standard 14 days of tecovirimat, such as cidofovir, brincidofovir, or intravenous vaccina immune globulin.
PubMed: 38651138
DOI: 10.1093/ofid/ofae138 -
Ear, Nose, & Throat Journal Apr 2024Peritonsillar abscesses (PTAs) are typically caused by group A or mixed oral flora. is a part of the normal vaginal microbiome, and overgrowth can cause bacterial...
Peritonsillar abscesses (PTAs) are typically caused by group A or mixed oral flora. is a part of the normal vaginal microbiome, and overgrowth can cause bacterial vaginosis. We present a case of recurrent PTA with superinfection, which occurred after the patient performed oral sex on a female after incision and drainage of her initial PTA. The patient continued to have recurrent PTAs until was identified, and antibiotic coverage was broadened to cover both group A and . This case highlights the importance of culturing PTA aspirate for directed antibiosis in persistent or recurrent infections. The rare superinfection also raises the question of advising abstinence from oral-genital contact after oral procedures to minimize risk of superinfection.
PubMed: 38647231
DOI: 10.1177/01455613241246486 -
Virus Research Jul 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has posed significant challenges to global...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has posed significant challenges to global health. While much attention has been directed towards understanding the primary mechanisms of SARS-CoV-2 infection, emerging evidence suggests co-infections or superinfections with other viruses may contribute to increased morbidity and mortality, particularly in severe cases of COVID-19. Among viruses that have been reported in patients with SARS-CoV-2, seropositivity for Human cytomegalovirus (HCMV) is associated with increased COVID-19 risk and hospitalization. HCMV is a ubiquitous beta-herpesvirus with a seroprevalence of 60-90 % worldwide and one of the leading causes of mortality in immunocompromised individuals. The primary sites of latency for HCMV include CD14 monocytes and CD34 hematopoietic cells. In this study, we sought to investigate SARS-CoV-2 infection of CD14 monocytes latently infected with HCMV. We demonstrate that CD14 cells are susceptible and permissive to SARS-CoV-2 infection and detect subgenomic transcripts indicative of replication. To further investigate the molecular changes triggered by SARS-CoV-2 infection in HCMV-latent CD14 monocytes, we conducted RNA sequencing coupled with bioinformatic differential gene analysis. The results revealed significant differences in cytokine-cytokine receptor interactions and inflammatory pathways in cells superinfected with replication-competent SARS-CoV-2 compared to the heat-inactivated and mock controls. Notably, there was a significant upregulation in transcripts associated with pro-inflammatory response factors and a decrease in anti-inflammatory factors. Taken together, these findings provide a basis for the heightened inflammatory response, offering potential avenues for targeted therapeutic interventions among HCMV-infected severe cases of COVID-19. SUMMARY: COVID-19 patients infected with secondary viruses have been associated with a higher prevalence of severe symptoms. Individuals seropositive for human cytomegalovirus (HCMV) infection are at an increased risk for severe COVID-19 disease and hospitalization. HCMV reactivation has been reported in severe COVID-19 cases with respiratory failure and could be the result of co-infection with SARS-CoV-2 and HCMV. In a cell culture model of superinfection, HCMV has previously been shown to increase infection of SARS-CoV-2 of epithelial cells by upregulating the human angiotensin-converting enzyme-2 (ACE2) receptor. In this study, we utilize CD14 monocytes, a major cell type that harbors latent HCMV, to investigate co-infection of SARS-CoV-2 and HCMV. This study is a first step toward understanding the mechanism that may facilitate increased COVID-19 disease severity in patients infected with SARS-CoV-2 and HCMV.
Topics: Humans; Monocytes; Cytomegalovirus; Lipopolysaccharide Receptors; SARS-CoV-2; COVID-19; Cytomegalovirus Infections; Superinfection; Virus Latency; Inflammation; Coinfection; Cytokines; Virus Replication
PubMed: 38642618
DOI: 10.1016/j.virusres.2024.199375