Timing of #Remdesivir Initiation and Clinical #Outcomes in Hospitalized Patients with #COVID19 Who Are at High Risk of Disease Progression in #Japan: A Health Insurance Claims Database Study

 

Abstract

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan.

Source: 

Link: https://www.mdpi.com/1999-4915/18/4/479

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Emergence of D1.1 #reassortant #H5N1 avian #influenza viruses in North #America

 

Abstract

Since 2021, highly pathogenic avian influenza viruses (HPAIVs) belonging to H5N1 clade 2.3.4.4b have circulated widely in North American wild birds and repeatedly spilled over into mammals. In 2025, the first H5N1-associated deaths in humans were recorded in the Western hemisphere, raising questions about how the ongoing evolution of the virus in wild birds impacts spillover risk. Here, our analysis of 21,471 H5N1 genomes identified an evolutionary shift in mid-2024, driven by interhemispheric migration from Asia and reassortment with new antigens. The genotypes that dominated the early years of North America's H5N1 epizootic traced their ancestry back to Europe, but Asia was the source of new "D1.1" genotype viruses that (a) spread faster, (b) have higher reassortment potential, (c) a broader host range, (d) repeatedly spill over to bovines, and (e) cause severe disease in humans, including non-farm workers.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Research Foundation - Flanders, https://ror.org/03qtxy027, G098321N, G0E1420N

European Union Horizon 2023 RIA project LEAPS, 101094685

DURABLE EU4Health project 02/2023-01/2027, 101102733

Fonds National de la Recherche Scientifique, F.4515.22

European Union Horizon 2020 project MOOD, 874850

Centers of Excellence for Influenza Research and Response, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, 75N93021C00014

Source: 

Link: https://www.biorxiv.org/content/10.64898/2025.12.19.695329v2

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#Outdoor roaming of owned #cats elevates #risk of zoonotic #pathogen #exposure: A global synthesis

 

Abstract

Domestic animals play a central role in pathogen transmission at the human–wildlife interface. Domestic cats, in particular, are uniquely consequential in disease spillover dynamics due to their global distribution, large, human-subsidized free-roaming populations, and high contact rate with humans, domestic animals, and wildlife. However, the extent to which human ownership and management mitigate this spillover risk remains a key knowledge gap. To address this gap, we conducted a global systematic review and quantitative synthesis of the prevalence and diversity of zoonotic pathogens in indoor-only, outdoor-owned (roaming unsupervised), and unowned (feral or stray) cats. Our dataset comprised 174,064 individuals from 88 countries, representing 124 pathogen species, 97 of which are zoonotic. Using generalized linear models within a Bayesian framework and rarefaction analyses, we show that ownership provides limited protection against zoonoses when owned cats have unsupervised outdoor access. Outdoor-owned cats were 3–5 times more likely to carry zoonotic pathogens than indoor-only cats, and, notably, had infection odds statistically equivalent to those of feral cats, despite receiving presumed veterinary care and feeding. Feral cats carried the highest pathogen diversity, however, outdoor-owned cats still harbour 1.5 times the helminth richness of indoor cats, highlighting their potential as effective bridges for pathogen spillover. With approximately 62% of owned cats roaming freely worldwide, and rates exceeding 90% in some regions, these findings reveal a major yet overlooked route of zoonotic risk. Public health and One Health frameworks have traditionally focused on feral cats; however, our results highlight the need to explicitly incorporate owned outdoor cats into zoonotic disease prevention strategies by restricting unsupervised roaming and promoting responsible ownership practices. Without such integration, current frameworks risk overlooking a pervasive and preventable pathway for pathogen transmission at the human–wildlife–domestic animal interface.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014160

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#Surveillance and #control efficacy of the Bergerac, #France, 2025 #chikungunya #outbreak

 

Abstract

The spread of the highly invasive mosquito, Aedes albopictus, across Europe, combined with climate change and human travel and trade, has led to new epidemic threats from mosquito-borne viruses, most significantly dengue and chikungunya, which are increasing in frequency and magnitude. In 2025, mainland France has seen a record number of autochthonous cases and outbreaks of chikungunya, spread across multiple locations, primarily introduced by travellers from the French Overseas Territory of La Réunion which is experiencing severe chikungunya outbreaks. Here, we describe one of the largest French outbreaks and subsequent control measures in the city of Bergerac, Dordogne, which resulted in 102 cases as of 5th November 2025. We apply a climate-driven mathematical model for Ae. albopictus and chikungunya virus transmission to the Bergerac 2025 outbreaks, comparing outputs to case data. The model suggests that the initial control measures in the first four weeks after the discovery of the outbreak, limited in their intervention radius and intensity, had little effect on reducing the number of cases, given the high incidence and the wide geographic extent of viral circulation. However, subsequent more widespread and intense control efforts, combined with likely increased public awareness, substantially reduced case numbers. These findings underscore the need to tailor control measures to intensity and scale of viral circulation combined with effective preventive and proactive arbovirus surveillance. Adulticides combined with public awareness campaigns can be effective for public health protection and are an important part of mitigating against the risk of Aedes-borne arboviruses and the ongoing outbreaks in mainland France.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014184

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Uncomplicated #malaria as a #risk factor for #COVID19 duration and severity in western #Kenya and #Burkina Faso (MALCOV): a prospective cohort study

 

Summary

Background

The relationship between malaria and COVID-19 varies across different clinical scenarios; historical malaria exposure might protect against severe COVID-19, whereas co-infection in hospitalised patients with severe disease might increase mortality. Interactions between non-severe malaria and COVID-19 remain poorly understood. We conducted a cohort study among COVID-19 patients of all ages in western Kenya and Burkina Faso to assess the effects of acute, uncomplicated Plasmodium falciparum malaria co-infection on COVID-19 outcomes in ambulatory patients.

Methods

Participants with laboratory-confirmed SARS-CoV-2 infection (positive rapid antigen test or reverse transcription quantitative real-time PCR [RT-qPCR]) were tested for malaria by rapid antigen tests with confirmatory microscopy. Patients with COVID-19 and malaria co-infection received artemether–lumefantrine or pyronaridine–artesunate. COVID-19 symptom course was assessed daily using FLU-PRO Plus (a validated patient-reported outcome instrument) until day 14. Viral load was measured by RT-qPCR on days 0, 3, 7, 14, and 28. The primary endpoint was time to symptom resolution on the FLU-PRO Plus. Analyses were adjusted for country, age, disease severity, and viral load.

Findings

Between Jan 8, 2021 and Jan 24, 2022, we screened 5161 participants and recruited 756 with COVID-19. 742 participants with valid malaria tests were enrolled, of which 151 (20%) had malaria co-infection and the remaining 591 (80%) did not have malaria. Patients with malaria were younger (49 [32%] aged <15 years) than those without malaria (35 [6%]; p<0·0001). Time to symptom resolution was similar between those with malaria (median 9 days [IQR 5–13]) and those without (10 days [IQR 6–13]; adjusted hazard ratio [aHR] 1·14 [95% CI 0·91–1·42]; p=0·26). Three (2%) patients with malaria and nine (2%) without malaria were hospitalised; two (1%) with malaria and three (1%) without malaria died, four from acute respiratory distress syndrome and one (in the no malaria group) from perforated peptic ulcer complicated by anaemia. Participants with malaria more frequently reported moderate-to-severe symptoms at enrolment (68% vs 60%; p=0·074), but overall symptom duration was similar (adjusted incidence rate ratio 0·95 [95% CI 0·86–1·05]; p=0·31). Previous malaria exposure significantly modified outcomes, with patients with malaria co-infection and previous exposure having faster symptom clearance than those without previous exposure (pinteraction=0·042). SARS-CoV-2 clearance was slower in the malaria group by day 7 (aHR 0·69 [95% CI 0·51–0·94]; p=0·017) but was similar between groups by day 28 (adjusted risk ratio 0·99 [95% CI 0·79–1·24]; p=0·95).

Interpretation

This study shows that acute uncomplicated malaria co-infection does not adversely affect COVID-19 progression when appropriately treated. Moreover, serological evidence confirms that previous lifelong malaria exposure might provide some protection, with exposed individuals having faster symptom resolution.

Funding

Gates Foundation.

Translation

For the French translation of the abstract see Supplementary Materials section.

Source: 

Link: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(25)00541-8/fulltext

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A natural five-amino-acid insert at the S2’ #cleavage site of #MERS-CoV #spike enhances viral membrane fusion

 

Highlights

• A novel 5-aa insert, TSGVF, is present at the S2’ cleavage site of the spike protein of MERS-CoV from dromedary camels.

• Pseudovirus-based entry assays showed that the TSGVF insert increases viral entry efficiency in different human cells.

• Pseudovirus with TSGVF insert at the S2’ cleavage site showed strong resistance to TMPRSS2 inhibitor.

• The natural occurrence of TSGVF insert at the spike S2’ cleavage site enhances viral membrane fusion and syncytia formation.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1995820X26000611?via%3Dihub

____

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#Ocular findings in Northern #Gannets following an #outbreak of high pathogenicity avian #influenza #H5N1

 

Abstract

During 2021-2022, high pathogenicity avian influenza (HPAI) caused mass mortality in wild birds across Europe, with Northern Gannets (Morus bassanus) among the most affected. Following the outbreak, unusual alterations in the species' characteristic pale iris were observed in some individuals. Opportunistically captured gannets on Bass Rock (n=52), selected to represent a range of iris pigmentation, were examined. Slit-lamp biomicroscopy, indirect ophthalmoscopy, rebound tonometry and photography were performed. Iris pigmentation was classified as normal, mottled or black. Eleven birds underwent avian influenza virus (AIV) serology. Histopathology was performed on two eyes. Abnormal iris pigmentation was found in 74% of adult and immature gannets, with 61% affected bilaterally. Additional signs consistent with uveitis were present in 77% of affected birds. Iris pigmentation abnormalities were positively associated with AIV H5 seropositivity (Fishers exact test, P=0.018). Histopathology from affected eyes showed increased melanin deposition and disorganisation, including loss of a distinct anterior layer of melanocytic cells and hypertrophy of melanocytes within the iris stroma. Field conditions limited uniform lighting and concurrent serology. Iris pigmentation changes were associated with prior HPAI exposure and frequently accompanied by signs of uveitis, suggesting iris alterations may indicate past infection and potential chronic sequelae.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.15.718625v1

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Frequent seasonal #reassortment between high and low path #viruses drives the diversification of #influenza #H5N1

 

Abstract

Since 2021, highly pathogenic (HPAI) H5N1 viruses have spread across the Americas, diversifying via reassortment into new genotypes that have spilled into humans and livestock, raising fears of a new influenza pandemic. Pandemic lineages are typically associated with reassortment, but we currently have limited understanding of where and when reassortment is expected to occur, which limits our ability to assess pandemic risks. Using a dataset of 9,052 full-genome sequences, we show that reassortment and novel genotype formation are associated with seasonal variation in low pathogenicity avian influenza (LPAI) cases and with the spatial and host distributions of viral transmission. We pinpoint ducks, geese, and the Central flyway as frequent sources of new genotypes, and show that reassortment rates vary seasonally, driven by mixing between high- and low-pathogenicity viruses. Cattle spillover genotypes (B3.13 and D1.1) evolved during periods of high reassortment, implicating reassortment as a common occurrence in lineages evolving during particular time periods. Together, these findings reframe reassortment as a predictable ecological process, with direct implications for how surveillance and pandemic risk assessment should be designed.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

US Centers for Disease Control Insight Net, CDC-RFA-FT-23-0069

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.17.719307v1

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#Infection of the #bovine mammary #gland by avian #H5N1 subclade 2.3.4.4b #influenza viruses

 

Abstract

The emergence of the panzootic clade of highly pathogenic avian influenza H5N1 (2.3.4.4b) in 2020 marked a major expansion in the host range of influenza A viruses (IAVs), raising concerns about further cross‑species transmission events and zoonotic spillover. Introduction of 2.3.4.4b viruses into U.S. dairy herds has resulted in widespread circulation, accompanied by reduced milk yield, mastitis, and high viral loads in milk. Notably, virus circulation in dairy cattle represents a novel route for mammalian adaptation and transmission that has already led to more than 40 human cases in the U.S. since 2024. Here, we investigated whether avian clade 2.3.4.4b viruses could infect mammary tissue from Aberdeen Angus, Holstein Friesian, and Limousin cattle, three breeds commonly farmed in Europe, the Americas, and Oceania. Using mammary gland explants, we inoculated tissues with attenuated reassortant viruses expressing the haemagglutinin and neuraminidase glycoproteins of three 2.3.4.4b viruses that predated the emergence of H5N1 in US cattle: A/chicken/England/053052/2021 (AIV07), A/chicken/Scotland/054477/2021 (AIV09), and A/chicken/England/085598/2022 (AIV48). Infected epithelial cells were identified using immunohistochemistry in explants from both the teat and gland cistern for all three breeds following infection with AIV09 and AIV48, indicating that mammary tissue from each of the three tested cattle breeds cattle is permissive to H5N1 infection. Lectin staining showed expression of both α2,3‑linked and α2,6‑linked sialic acids in the mammary tissue of all donors showing that all three breeds have the potential to support infection with both avian-adapted and mammalian adapted IAVs. Together, these findings demonstrate that mammary glands from both beef and dairy cattle breeds are permissive to infection with avian‑adapted and mammalian-adapted H5N1 viruses and highlight the potential for this tissue to act as a mixing vessel for IAV reassortment, underscoring the need to include cattle in ongoing H5N1 surveillance and risk‑assessment frameworks.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Medical Research Council, https://ror.org/03x94j517, MR/Y03368X/1, MR/Y03368X/1, MC_UU_0034/2, MC_UU_0034/3, MC_UU_0034/1

Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/V004697/1

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.16.718897v1

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Acquisition of specific #human respiratory tract binding of 2.3.4.4b #H5N1 #hemagglutinins requires multiple #mutations

 

Abstract

It has been suggested that the hemagglutinin of the human-infecting cattle-derived 2.3.4.4b virus A/Texas/34 (H5TX) requires only one mutation, namely Q226L, to switch from binding avian-type to human-type receptor preference. In this study, we examined the binding of H5TX Q226L, along with other key mutations, to sections of human trachea. We conclude that, while H5TX Q226L can bind human-type receptors, more than a single mutation is required for this protein to bind to human respiratory tract tissue. We also report changes in receptor-binding specificity of another 2.3.4.4b HA mutant, H5FR Q226L, associated with the presence of a multibasic cleavage site. This study offers insight into the determinants of evolution towards human-type receptor binding in currently circulating H5Nx viruses. It also emphasizes the importance of testing individual strains using additional methods, including tissue-based approaches, alongside synthetic glycans.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NWO, OCENW.M20.106

Horizon, 862605

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.16.718875v1

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Susceptibility of wild and domestic #songbirds to #Usutu virus

Abstract

Usutu virus (USUV) is an emerging mosquito-borne orthoflavivirus that can cause neuroinvasive disease in humans and wild birds. USUV clusters phylogenetically within the Japanese encephalitis virus serocomplex, sharing antigenic and ecological similarity with West Nile virus (WNV). USUV is maintained in an enzootic cycle primarily involving passerine birds and Culex spp. mosquitoes. USUV was first isolated in South Africa in 1959 and has since spread throughout Africa and Europe, causing mortality and disease in several wild bird populations, specifically the Eurasian blackbird (Turdus merula). To understand transmission and pathogenesis of USUV in birds, we sought to develop passerine bird models of infection using wild-caught house finches (Haemorhous mexicanus), wild-caught American robins (Turdus migratorius), domestic canaries (Serinus canaria domestica), and captive-bred zebra finches (Taeniopygia guttata). Birds were inoculated with one or two isolates of USUV and viremia was measured. House finches, American robins, and canaries were susceptible to USUV, with 100% of inoculated birds developing viremia. These avian species reach viremias that have the potential to infect Cx. quinquefasciatus mosquitoes. Clinical disease and histopathological evidence of disease were severe in American robins and moderate to severe in canaries, with limited disease in house finches. However, zebra finches inoculated with one isolate of USUV did not develop detectable viremia. These findings provide additional tools for studying USUV enzootic transmission and pathogenesis in passerine birds.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014213

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Cross - #protection against highly pathogenic avian #influenza #H5N1 virus from seasonal influenza #vaccines: a systematic review and meta-analysis of #ferret studies

 

ABSTRACT

The recent surge in spillover events of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b to humans and mammals in North America has raised urgent pandemic concerns. Human H5N1 vaccines are unavailable in most countries. We synthesized data from ferret challenge trials to evaluate whether widely available seasonal influenza vaccines confer cross-protection against lethal H5N1 infection. We systematically searched PubMed, Embase, and Web of Science for ferret studies of lethal H5N1 challenge published up to 5 July 2025 (PROSPERO #CRD42024520346). Random-effects meta-analyses were conducted to compare vaccine efficacy (VE) of seasonal influenza vaccines and H5N1 vaccines against H5N1-related mortality. Seroprotection was defined as a neutralizing antibody titre of ≥1:40. We identified 35 studies (157 trials). Seasonal influenza vaccines without N1 did not confer significant cross-protection (five trials; VE 14.8%, 95% CI –3.6 to 30.0). In contrast, VE was 73% for N1-containing seasonal influenza vaccines (19 trials; 95% CI 54–84) and 77% for H5N1 vaccines overall (133 trials; 95% CI 72–82) (p = 0.52). The VE of N1-containing seasonal influenza vaccines was modestly lower than that of H5N1 vaccines with seroprotection (88%; 66 trials; 95% CI 84–91; p = 0.009), but comparable to H5N1 vaccines that did not achieve seroprotection (63%; 67 trials; 95% CI 52–71; p = 0.29). The VE of seasonal influenza vaccines against H5N1 was robust across sensitivity analyses, with no evidence of publication bias (p = 0.99). Seasonal influenza vaccines significantly reduce H5N1-associated mortality in ferret trials, suggesting the cross-protection potential of currently available vaccines. Human studies are warranted.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2654278

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#SARS-CoV-2 #vaccination and #infection elicit cross-neutralizing responses against clade 3 and 4 #sarbecoviruses

 

Abstract

Two sarbecoviruses, SARS-CoV-1 and SARS-CoV-2 that engage ACE2 through their receptor-binding domains, have caused major human outbreaks. The pandemic potential of sarbecoviruses has prompted the discovery and classification of bat and other zoonotic sarbecoviruses that are also able to use human ACE2 or ACE2 ortholog receptors for infection. However, the current human immunological landscape reactive to these SARS-CoV-2-related viruses is not well profiled. Using a panel of pseudotyped lentiviruses expressing only spike proteins, we assess serum neutralization activity against clade 3 and 4 (also designated as clade 1c) receptor binding domain classified sarbecoviruses in a cohort who received a primary series of COVID-19 mRNA vaccines as well as individuals before and after infection with BA.5 or XBB.1.5 variants. Detectable neutralizing responses against clade 3 and 4 sarbecoviruses are observed in both vaccinees and convalescents and are comparable in magnitude to titers against SARS-CoV-2 variants. Infection with XBB.1.5 increases neutralization titers against SARS-CoV-2 variants as well as against clade 3 and 4 sarbecoviruses. Collectively, our findings suggest that the current immunologic landscape of vaccination and infection may confer some level of immunity against a variety of clade 3 and 4 sarbecoviruses, which should inform future pandemic response and pan-sarbecovirus countermeasure efforts.

Source: 

Link: https://www.nature.com/articles/s41467-026-71662-y

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The virus entry #inhibitor ARN-75039 provides therapeutic #protection against #Lassa virus infection in guinea pigs

 

Abstract

Lassa virus (LASV), a member of the Arenaviridae family, causes Lassa fever. There are no vaccines available for prevention of Lassa fever, and the primary therapeutic for treatment (ribavirin) has questionable antiviral activity and no formal approval for use. Here, we evaluated ARN-75039, an orally bioavailable broad-spectrum mammarenavirus entry inhibitor, against LASV infection in outbred Hartley guinea pigs exposed to a guinea pig–adapted LASV. ARN-75039 was administered for 14 days either 3 or 7 days postexposure (dpe) to LASV. In the first two studies, once-daily dosing at 3 dpe provided protection against lethal infection. A third study with twice-daily dosing at 7 dpe also achieved protection. Both drug regimens offered 100% protection at the lowest tested doses of 3.75 mg/kg (once-daily administration) or 7.5 mg/kg (twice-daily administration). ARN-75039–treated animals exhibited minimal disease signs and undetectable viremia. These results suggest that ARN-75039, for which a phase 1 human clinical trial has now been completed, may offer robust protection against LASV infection.

Source: 

Link: https://www.science.org/doi/10.1126/scitranslmed.adx0938

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Highly Pathogenic Avian #Influenza #H5N1 Virus #RNA in #Bovine #Semen, #California, #USA, 2024

 

Abstract

Since March 2024, highly pathogenic avian influenza (HPAI) A(H5N1) virus has infected dairy cattle in the United States, prompting concern about novel transmission routes. During an outbreak in California, HPAI H5N1 RNA was detected in an asymptomatic bull’s semen. Although infectious virus was not isolated, semen-associated transmission risks and biosecurity practices remain a concern.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/5/25-1639_article

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#SARS-CoV-2 and #MERS-CoV disrupt #host #protein synthesis via nsp1 with differential effects on the integrated stress response

 

Significance

Coronaviruses cause disease across a wide range of animal species and the human coronaviruses SARS-CoV-2 and MERS-CoV have caused epidemics of severe respiratory illness. Thus, it is imperative to understand how these viruses antagonize host responses and cause lethal disease. We show here that the betacoronavirus nonstructural protein 1 (nsp1) promotes shutdown of host protein synthesis while preserving viral protein synthesis and, in addition, promotes degradation of host mRNAs. However, SARS-CoV-2 and MERS-CoV differ in their ability to manipulate the host integrated stress response, indicating that it is important to understand detailed coronavirus–host interactions and how they differ even between lethal coronaviruses. Such insights will inform the development of antiviral therapeutics to treat and prevent current and future coronavirus outbreaks.

Abstract

Coronaviruses pose a serious threat to public health, driving the need for antiviral therapeutics and vaccines. Therefore, it is paramount to understand how this family of viruses evades cellular antiviral responses and establishes productive infection. The conserved coronavirus nonstructural protein 1 (nsp1) has been shown to inhibit host protein synthesis and, in some coronaviruses, promote host messenger RNA (mRNA) degradation while viral mRNAs are protected. We showed previously that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces activation of host integrated stress response (ISR) kinases protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), which promote phosphorylation of eukaryotic initiation factor 2 (eIF2α) and consequent inhibition of host protein synthesis. In contrast, eIF2α remains unphosphorylated during Middle East respiratory syndrome coronavirus (MERS-CoV) infection. To investigate the interactions of nsp1 and the ISR kinases, we utilized recombinant SARS-CoV-2 and MERS-CoV expressing nsp1 with mutations in each of two conserved domains. Upon infection with SARS-CoV-2 nsp1 mutants, translation was shut down in wildtype (WT) and PKR knockout (KO) cells but rescued in PERK KO cells, likely due to reduced p-eIF2α. In contrast, translation was rescued during infection with the analogous MERS-CoV nsp1 mutants even in WT cells. Moreover, SARS-CoV-2 WT suppressed expression of GADD34, a negative regulator of eIF2α phosphorylation, while SARS-CoV-2 nsp1 mutants induced GADD34. In contrast, MERS-CoV WT induced GADD34. Utilizing single-molecule fluorescence in situ hybridization, we found that SARS-CoV-2 and MERS-CoV nsp1 promote host mRNA degradation during WT, but not nsp1 mutant, infection. Thus, SARS-CoV-2 and MERS-CoV differ in interactions with the ISR and nsp1 control of host protein synthesis.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2536296123?af=R

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#Vaccine-Elicited #Antibody Responses to #Influenza #H3N2 Subclade K

 

{Summary}

Influenza A(H3N2) subclade K (J.2.4.1) is a genetic branch of H3N2 with 11 mutations in hemagglutinin compared with the A/H3N2/Croatia/10136RV/2023 (H3N2 CR/23) vaccine strain, of which 8 mutations are on the hemagglutinin head surface (...) (...). As of February 2026, influenza A viruses currently represent approximately 96.3% of circulating influenza strains in the US, with H3N2 accounting for 88.4% of influenza isolates and subclade K comprising 91.5% of H3N2 isolates. The rapid expansion of H3N2 subclade K represents a major public health concern. This study reports antibody responses to H3N2 subclade K and other influenza strains before and after influenza vaccination.

(...)

Source: 

Link: https://jamanetwork.com/journals/jama/article-abstract/2846268

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#Population #immunity to clade 2.3.4.4b #H5N1 is dominated by anti - #neuraminidase #antibodies

 

ABSTRACT

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)- and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting antibodies were absent, we detected widespread binding and functional NA antibodies against N1 neuraminidases from clade 2.3.4.4b H5N1 viruses. Neuraminidase inhibition (NI) titers were highest against North American D1.1 genotype N1 viruses and correlated strongly with neutralizing activity, whereas HA-binding antibodies did not. An additional N-linked glycosylation site, as found in the NA of a human D1.1 isolate from British Columbia, reduced susceptibility to NI antibodies. Antibodies titer to N5 from H5N5 were low to minimal. These findings indicate that population-level immunity to clade 2.3.4.4b H5 viruses is dominated by NA-directed antibodies, with important implications for pandemic risk assessment.

IMPORTANCE

Understanding how pre-existing human immunity shapes susceptibility to emerging influenza viruses is central to pandemic preparedness. Here, we determined that human sera contain widespread, functional antibodies targeting H5N1 neuraminidase, which correlate with virus neutralization, whereas HA-directed responses are limited. We further show that acquisition of an NA glycosylation site reduces antibody inhibition, highlighting a potential pathway for immune evasion. These results identify neuraminidase-specific immunity as a major immunological barrier to severe H5N1 disease in humans and emphasize the need to incorporate NA antigenicity into influenza surveillance, risk assessment, and next-generation vaccine design.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00445-26

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