Hematogenous #neuroinvasion and genotype-dependent #transmission of #influenza A #H5N1 viruses in the #cat host

 

Abstract

The spillover of highly pathogenic avian influenza (HPAI) A H5N1 virus to mammalian hosts raises major concerns due to its pandemic potential. Cats are frequently affected mammals, often succumbing to systemic and neurological disease. Here, we characterized the pathogenesis and transmissibility of two H5N1 genotypes, B3.13 and D1.1, in cats. Infected cats exhibited high-level viremia and virus shedding in nasal, oral, and fecal secretions were consistently detected. The virus replicated initially in the upper respiratory tract and lungs, followed by systemic dissemination and neuroinvasion. Notably, the virus crossed the blood-brain-barrier by infecting endothelial cells, spreading to astrocytes and neurons, causing multifocal encephalitis. D1.1-virus infection caused protracted disease with lower shedding and no transmissibility, whereas B3.13 virus caused rapid onset with efficient shedding and transmission. These findings reveal critical H5N1 neuropathogenesis mechanisms and highlight mammalian transmission potential in a species with close human contact.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.02.21.707182v1

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Emergence of #Parechovirus-A5 #CNS #infections in #children from #Kansas City, #Missouri, #USA

HIGHLIGHTS

• PeV-A5 was the predominant PeV-A genotype detected from CSF/blood in 2024 at CM-KC.

• CM-KC PeV-A5 sequences resemble PeV-A5 sequences reported in Sapporo City, Japan, in 2018.

• The highest number of PeV-A5 detections within a single year in the USA.

ABSTRACT

Background

Parechovirus-A5 (PeV-A5) blood and central nervous system (CNS) infections are rare in the United States of America (USA) and globally. We report an emergence of PeV-A5 infections among infants in Kansas City, Missouri, in 2024.

Methods

Cerebrospinal fluid (CSF) and blood samples from infants were tested for Parechovirus (PeV-A) in 2024 as a part of standard of care at Children's Mercy Kansas City (CM-KC). PeV-A testing included a two-step reverse transcriptase-polymerase chain reaction, and genotyping was conducted using Sanger sequencing. We analyzed the amino acid sequences and phylogeny of the 2024 PeV-A viruses and described the clinical characteristics of PeV-A infected infants.

Results

Among 211 CSF and 46 blood samples from 248 patients, 10 (4%) PeV-A infected patients were detected (8 CSF, 2 blood). Genotyping was successful for viruses from 9 PeV-A infected patients, with 8 identified as PeV-A5 (6 CSF, 2 blood) and 1 as PeV-A4 (CSF). PeV-A5 viral sequences from CM-KC clustered with other known PeV-A5 sequences, being most similar (>97%) to a PeV-A5 viral sequence from Sapporo City, Japan, in 2018. PeV-A5 detections from CM-KC occurred with a summer-fall seasonality. All 8 PeV-A5 infected patients had symptoms of rash with less irritability and lower maximum temperature when compared to previous PeV-A3 and PeV-A4 infected patients at CM-KC.

Conclusions

PeV-A5 emerged as the predominant PeV-A genotype detected from sterile sites (CSF, blood) in infants in Kansas City, Missouri in 2024, representing the highest number of PeV-A5 systemic illness in infants in the USA within a year.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000770?dgcid=rss_sd_all

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#Neurologic Manifestations Associated with #Parvovirus B19 #Epidemic, #Madrid, #Spain, 2024

Abstract

A reemergence of parvovirus B19 infections in Spain in early 2024 prompted a 10-year review of the virus at a tertiary center. We identified 8 case-patients with neurologic manifestations who had parvovirus B19 in cerebrospinal fluid. Early recognition and management of parvovirus B19–associated neurologic conditions will help yield favorable outcomes.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0278_article

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#Influenza A Virus #infection is associated with TDP-43 #pathology and neuronal #damage in the #brain

Abstract

Viral pandemics such as COVID-19 have demonstrated long-term neurological consequences, including memory impairment and depression, emphasizing the importance of understanding virus-brain interactions [1]. Similar concerns have been raised for Influenza A virus (IAV), which has been implicated in neurodegenerative disorders [2, 3]. In this study, we investigated the neuropathological effects of highly pathogenic avian influenza (HPAI) H5N1 and H5N8 strains in a mouse model. Although viral RNA was detected in the brain post-infection, no viral proteins were found, suggesting limited or transient brain replication. Despite this, infected brains showed significant neuronal damage, including axonal loss and nuclear condensation, as evidenced by immunofluorescence and Nissl staining. We also observed pathological changes in TDP-43, including conformational alterations and increased phosphorylation, which required antigen retrieval for detection, features reminiscent of those found in frontotemporal dementia and amyotrophic lateral sclerosis [4, 5]. Transcriptomic analysis further revealed strain-specific host responses, including activation of interferon-related genes and downregulation of microtubule-associated pathways. These findings suggest that IAV infection can trigger hallmarks of neurodegeneration in the absence of persistent viral protein expression, possibly through host-driven mechanisms. Our results underscore the need for further investigation into virus-induced molecular pathways contributing to neurodegenerative disease.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.30.662477v1

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#Monkeypox virus spreads from #cell-to-cell and leads to #neuronal #death in human neural #organoids

Abstract

In 2022-23, the world witnessed the largest recorded outbreak of monkeypox virus (MPXV). Neurological manifestations were reported alongside the detection of MPXV DNA and MPXV-specific antibodies in the cerebrospinal fluid of patients. Here, we analyze the susceptibility of neural tissue to MPXV using human neural organoids (hNOs) exposed to a clade IIb isolate. We report susceptibility of several cell types to the virus, including neural progenitor cells and neurons. The virus efficiently replicates in hNOs, as indicated by the exponential increase of infectious viral titers and establishment of viral factories. Our findings reveal focal enrichment of viral antigen alongside accumulation of cell-associated infectious virus, suggesting viral cell-to-cell spread. Using an mNeonGreen-expressing recombinant MPXV, we confirm cell-associated virus transmission. We furthermore show the formation of beads in infected neurites, a phenomenon associated with neurodegenerative disorders. Bead appearance precedes neurite-initiated cell death, as confirmed through live-cell imaging. Accordingly, hNO-transcriptome analysis reveals alterations in cellular homeostasis and upregulation of neurodegeneration-associated transcripts, despite scarcity of inflammatory and antiviral responses. Notably, tecovirimat treatment of MPXV-infected hNOs significantly reduces infectious virus loads. Our findings suggest that viral disruption of neuritic transport drives neuronal degeneration, potentially contributing to MPXV neuropathology and revealing targets for therapeutic intervention.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61134-0

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#Glial cells promote #infection by #neurotropic #Influenza A viruses in vitro

Abstract

Although influenza A viruses (IAV) are notorious respiratory pathogens, some IAV strains can reach and replicate in the central nervous system (CNS) in vivo. In particular, highly pathogenic avian influenza viruses (HPAIV) pose a threat for future pandemics and are linked to greater neurotropic potential. Moreover, neurotropic IAV strains have shown a more significant impact on the onset and pathogenesis of neurodegenerative diseases (NDD). However, despite its clinical relevance, the dynamics and cellular tropism of IAV infection in the CNS are not well understood. In this study, we analyzed the replication of HPAIV H7N7 in vitro using a primary murine triple co-culture system comprising neurons, astrocytes, and microglia. We found that microglia become highly infected early on and induce a strong pro-inflammatory response before undergoing apoptosis. Using fluorescence microscopy with automated single-cell profiling, we found that, in contrast to non-neurotropic H3N2, the H7N7 nucleoprotein accumulated in neuronal somata throughout the infection without being transported into dendrites or axons. A combination of single-cell and co-culture replication assays led us to conclude that astrocytes are the primary virus producers of HPAIV H7N7 in the CNS. Our results illuminate the acute phase of neurotropic IAV infection, highlighting its implications for the association between IAV and the development of neurodegenerative diseases.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.20.660606v1

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#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

{Excerpt}

A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments: M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic, expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries. The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat.1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts, including vertical transmissions, neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential.5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in extra-Amazonian Brazil, highlighting a potential synergistic mechanism of CNS invasion facilitated by HIV-induced immune dysregulation.

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Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00352-4/fulltext?rss=yes

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#Pathology of #Influenza A (#H5N1) #infection in #pinnipeds reveals novel tissue #tropism and vertical #transmission.

Abstract

In 2023, an unprecedented outbreak of highly pathogenic avian influenza (HPAI) H5N1 resulted in the death of thousands of pinnipeds along the Argentinean coast, raising concerns about its ecological and epidemiological impact. Here, we present clinical, pathological, and molecular findings associated with HPAI H5N1 infection in pinnipeds from Chubut, Argentina. Necropsies were conducted on three South American Sea Lions (SASLs) (Otaria flavescens) and one Southern Elephant Seal (SES) (Mirounga leonina), followed by histopathological, immunohistochemical and RT-sqPCR analyses. Neurological clinical signs were observed in two SASLs, with one also exhibiting respiratory distress. Neuropathological findings included lymphoneutrophilic meningoencephalomyelitis and choroiditis, neuronal necrosis, gliosis, hemorrhages, and perivascular cuffing. Viral antigen was localized in neurons, glial cells, choroid plexus epithelial cells, ependymal cells, and the neuropil. Systemic manifestations included HPAI-related necrotizing myocarditis in the elephant seal and placental necrosis in a sea lion, with fetal tissues testing positive for HPAIV. Pulmonary lesions were minimal, limited to bronchial glands in one individual. RT-sqPCR confirmed HPAI H5 in all tested animals. Our findings highlight the neurotropism of HPAI H5N1 in pinnipeds, and expand the known systemic effects of the virus, revealing new tissue tropism and vertical transmission.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.07.636856v1

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#SARS-CoV-2 #Infection of the #CNS: A Case Report

Abstract

Central nervous system (CNS) infections caused by SARS-CoV-2 are uncommon. This case report describes the clinical progression of a 92-year-old female who developed a persistent neuroinfection associated with SARS-CoV-2. The patient initially presented with progressive fatigue, catarrhal symptoms, and a fever (38.6 °C). Initial laboratory findings revealed hypoxemia (O2 saturation 79.8%), acidosis (pH 7.3), an elevated C-reactive protein (CRP) level of 14.8 mg/L, and a high D-dimer level (2.15 µg/mL). Nasopharyngeal (NP) antigen and RT-PCR tests confirmed SARS-CoV-2 infection, and an NP swab also detected penicillin- and ampicillin-resistant Staphylococcus aureus. She was admitted for conservative management, including oxygen supplementation, IV fluids, and prophylactic anticoagulation. Subsequently, she developed neurological symptoms—lethargy, discoordination, and impaired communication—without signs of meningism. Cerebrospinal fluid (CSF) analysis identified SARS-CoV-2 RNA (Ct = 29) on RT-PCR, while bacterial cultures remained negative. Treatment was intensified to include 10% mannitol, dexamethasone, and empiric ceftriaxone. Despite these interventions, the patient remained somnolent, with a Glasgow Coma Scale (GCS) score of 10. Upon discharge, her GCS had improved to 14; however, she continued to experience lethargy and cognitive issues, commonly described as “brain fog”. Inflammatory markers remained elevated (CRP 23 mg/L) and repeat RT-PCR of CSF confirmed a persistent SARS-CoV-2 presence (Ct = 31). This case underscores the potential for SARS-CoV-2 to cause prolonged CNS involvement, leading to persistent neurological impairment despite standard therapy. Further research is essential to clarify the pathophysiology of and determine optimal management for SARS-CoV-2 neuroinfections.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1962

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