The Judgment of Paris, Peter Paul Rubens (c.1636)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/peter-paul-rubens/the-judgment-of-paris-1636

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Emerging highly pathogenic #H5N1 #influenza triggers fibrotic #remodeling in #human #airway organoids

ABSTRACT

The ongoing outbreak of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b has affected at least 989 dairy herds across 17 states in the United States (U.S.) and resulted in 70 confirmed human infections, underscoring the urgent need to understand the pathogenesis and therapeutic interventions of emerging H5N1 viruses. In this study, we modelled infection with a highly pathogenic recombinant human A/Texas/37/2024 H5N1 (rHPh-TX H5N1) strain using human airway organoids (HAO) to investigate viral replication, innate immune response, infection-induced fibrogenesis, and potential therapeutic interventions. rHPh-TX H5N1 replicated efficiently in HAO, eliciting a robust interferon (IFN) response and pro-inflammatory cytokine production. Prolonged infection led to the accumulation of fibroblast-like cells surrounding infected regions, marked by increased alpha-smooth muscle actin (α-SMA) expression and upregulation of transforming growth factor-beta (TGF-β), indicative of fibroblast activation and extracellular matrix (ECM) remodelling. Compared to organoids infected with the pandemic A/California/04/09 H1N1 (pH1N1) strain, rHPh-TX H5N1 induced significantly higher expression of fibrosis-associated markers, including fibronectin (FN), collagen 1A (COL1A), collagen 3A (COL3A), metalloproteinases 2 and 9 (MMP2, and MMP9). Notably, the inhibition of Rho-associated coiled-coil-forming protein kinases (ROCK) signalling reduced fibrogenesis, with ROCK1 inhibition being more effective than ROCK2 inhibition. These findings highlight the potential of targeting ROCK signalling to mitigate H5N1-induced lung fibrosis, informing therapeutic strategies for severe influenza infections.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2532684#abstract

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Random #mutagenesis of #influenza #hemagglutinin identifies new sites which modulate its acid-stability and cleavability

Abstract

The structural instability of influenza hemagglutinin (HA) is related to its function in low pH-mediated membrane fusion, which requires prior cleavage of the premature HA0 by a host protease. The precise determinants underlying the stability and cleavability of HA remain to be fully understood and have implications for risk assessment of zoonotic influenza A viruses (IAV), viral transmissibility and vaccine production. To address this, we conducted random mutagenesis on early 2009 pandemic H1 HA, followed by selection of acid-stable viruses and detailed profiling of the mutant HAs. This resulted in identification of four mutations, which increase the acid-stability and decrease the fusion-promoting activity of H1 HA, without compromising viral entry and replication in cells. The newly recognized mutations are situated in the globular head, vestigial esterase and membrane-proximal part of H1 HA, in regions involved in the refolding of HA at low pH. A fifth mutation, D346N, is located in the cleavage loop and renders H1 HA0 12-fold resistant to trypsin activation, whereas its cleavage by transmembrane serine protease 2 (TMPRSS2) is not affected. Along this line, we found that the poor cleavage of H16 HA0, which is unusual in carrying an N346 residue, only applies when it is performed by extracellular proteases. Since H16 HA also exhibits a very low fusion pH, we propose that gull H16N3 virus may carry a much more stable HA than other avian IAVs. Collectively, our mutagenesis approach revealed new determinants of HA stability and cleavability, with relevance for viral surveillance and vaccine production.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.25.666873v1

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History of Mass Transportation: The FS E333 Three-Phase Electric Locomotive

Di Elio Cossetta - Ricordo quel binario, Alberto Cordara, Calosci-Cortona, Pubblico dominio,  https://commons.wikimedia.org/w/index.php?curid=34088072

Source: Wikipedia, https://it.wikipedia.org/wiki/Locomotiva_FS_E.333

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#Coronavirus Disease Research #References (by AMEDEO, July 26 '25)

 

Am J Respir Crit Care Med

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   Clin Infect Dis

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    Emerg Infect Dis

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    Int J Infect Dis

21. ZHANG Y, Guo J, Li Y, Song Y, et al
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22. COBO-VAZQUEZ E, Aguilera-Alonso D, Grandioso-Vas D, Gamell A, et al
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    PubMed         Abstract available
    
    
23. SIEBNER AS, Griesbaum J, Huus KE, Flugge J, et al
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    PubMed         Abstract available
    
    

    
    J Infect

24. ZHANG S, Liang H, Xu J, Chen B, et al
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    J Med Virol

25. MASTERS EA, Tang W, Kang I, Kosikova M, et al
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26. HERNANDEZ-ORTIZ OH, Naranjo AF, Cadavid JJV, Echavez GR, et al
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    J Virol

27. LI Q, Cai X, Li X, Zhang Y, et al
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    JAMA

28. SCHNEIDER L
    WHO Report Suggests Likely Zoonotic Origin of COVID-19, Doesn't Rule Out Lab Leak.
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    Lancet

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    Tracking development assistance for health, 1990-2030: historical trends, recent cuts, and outlook.
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    PubMed        
    
    

    
    Nature

32. CONROY G
    People's brains aged faster during the COVID pandemic - even the uninfected.
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33. RO C
    The COVID-19 pandemic transformed this scientist into a research-integrity sleuth.
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    PubMed        
    
    

    
    Radiology

34. KETAI L
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#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, July 26 '25)

 

Biochem Biophys Res Commun

1. KUSUMOTO T, Yotsukura M, Asakura T, Namkoong H, et al
   Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.
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   PubMed         Abstract available
   
   

   
   J Infect

2. SAITO R, Chon I, Sato I, Kawashima T, et al
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   PubMed         Abstract available
   
   

   
   J Infect Dis

3. SIMOES EAF, Suss RJ, Raje DV
   Human Metapneumovirus, Respiratory Syncytial Virus and Influenza Associated Pneumonia Hospitalizations in Colorado Adults Aged Over 50 Years: 2016-2023.
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   PubMed         Abstract available
   
   

   
   J Virol

4. MANNSVERK S, Villamil Giraldo AM, Kasson PM
   Influenza viral infection at the plasma membrane is restricted by lipid composition.
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5. SIMONICH CAL, McMahon TE, Ju X, Yu TC, et al
   RSV F evolution escapes some monoclonal antibodies but does not strongly erode neutralization by human polyclonal sera.
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6. ZHANG J, Li M, Cheng J, Wang Y, et al
   CypA inhibits respiratory syncytial virus (RSV) replication by suppressing glycolysis through the downregulation of PKM2 expression.
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7. POWELL BH, Witwer KW, Meffert MK
   Cellular miRNAs and viruses: trends in miRNA sequestering and target de-repression.
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8. CHEN Y, Shi Y, Zuo X, Dong X, et al
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10. LOKUGAMAGE KG, Zhou Y, Alvarado RE, Plante JA, et al
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11. COTTIGNIES-CALAMARTE A, Marteau F, He F, Belouzard S, et al
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12. MORGAN AL, Vu MN, Zhou Y, Lokugamage KG, et al
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13. FOSTER CSP, Walker GJ, Jean T, Wong M, et al
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14. NGUYEN D, Laidlaw SM, Dong X, Wand M, et al
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15. KALIN JH, Yin Y, Tran MT, Piassek M, et al
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    Lancet

16. 
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    PLoS Comput Biol

17. GONG R, Feng Z, Zhang Y
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18. KEITHLEY J, Choudhuri A, Adhikari B, Pemmaraju SV, et al
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19. KOLAR MR, Kobzarenko V, Mitra D
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    PLoS Med

20. KNOWLTON KU, Siegel LK, Barkauskas CE, Bhagani S, et al
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    PLoS One

21. MONROY-IGLESIAS MJ, Thavarajah R, Beckmann K, Josephs DH, et al
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23. KANG ZT, Yen PT, Cheong SA
    Indicator from the graph Laplacian of stock market time series cross-sections can precisely determine the durations of market crashes.
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24. WILLIAMS R, Bolton T, Jenkins D, Mizani MA, et al
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25. DORNEY J, Ebna Mannan I, Malicki C, Wisk LE, et al
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26. ROMAN-MONTES CM, Tamez-Torres KM, Guaracha-Basanez GA, Ordinola-Navarro A, et al
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27. THITY NT, Rahman A, Dulmini A, Yasmin MN, et al
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30. QI J, Huang D, Chen Y, Huang D, et al
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31. POLLETT SD, Colombo RE, Richard SA, Lalani T, et al
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    PubMed         Abstract available
    
    
32. GOTTLIEB M, Spatz ES, Yu H, Ebna Mannan I, et al
    Effects of long COVID on healthcare utilization.
    PLoS One. 2025;20:e0327218.
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33. DARAGHMEH DN, Salah A, Hamdan N, Zamareh A, et al
    Attitudes, beliefs, and practices regarding complementary and alternative medicine use: Influenza vaccine intake.
    PLoS One. 2025;20:e0320412.
    PubMed         Abstract available
    
    
34. ROBERTI J, Carmiol-Rodriguez P, Chan-Liang E, Aguilar-Vidrio OA, et al
    Enhancing tuberculosis treatment support: A thematic analysis of interactive messages in a digital adherence technology trial to identify needs, challenges, and strategies for improvement.
    PLoS One. 2025;20:e0326492.
    PubMed         Abstract available
    
    
35. TAVARES IC, Maria Guerreiro da Silva D, Ferreira Monteiro W, Janara Veras Lima K, et al
    Therapeutic itineraries and testimonies of COVID-19 patients in Manaus, the epicenter of the pandemic in the Brazilian Amazon.
    PLoS One. 2025;20:e0327127.
    PubMed         Abstract available
    
    

    
    Proc Natl Acad Sci U S A

36. MENON T, McQuilten HA, Samir J, Nguyen THO, et al
    Central memory T cells with key TCR repertoires and gene expression profiles dominate influenza CD8+ T cell pools across the human lifespan.
    Proc Natl Acad Sci U S A. 2025;122:e2501167122.
    PubMed         Abstract available
    
    
37. LEE AS
    Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.
    Proc Natl Acad Sci U S A. 2025;122:e2412246122.
    PubMed         Abstract available
    
    

    
    Vaccine

38. PICKERING H, Valli E, Carlock MA, Cappelletti M, et al
    Influenza strain-specific T cell responses longitudinally post-vaccination with FluZone.
    Vaccine. 2025;62:127506.
    PubMed         Abstract available
    
    

    
    Virus Res

39. SANZ-MUNOZ I, Martin-Toribio A, Garcia-Concejo A, Arroyo-Hernantes I, et al
    A 15-year study of neuraminidase mutations and the increasing of S247N mutation in Spain.
    Virus Res. 2025;358:199599.
    PubMed         Abstract available
    
    
40. CHEN Z, Cai M, Chai L, Li X, et al
    Anti-influenza Activity of Blumea Balsamifera (L.) DC. Extract: In Vitro and In Vivo Evaluation Against Multiple Influenza Virus Strains.
    Virus Res. 2025 Jul 20:199606. doi: 10.1016/j.virusres.2025.199606.
    PubMed         Abstract available
    

#Italy, West Nile Virus (#WNV) and #Usutu Virus Situation #Report, July 24 '25

{Summary}

-- During the Week 17-23 July 2025, Italy reported twenty-seven new cases of human infection with West Nile Virus.

-- Since the beginning of the epidemic season, thirty-two confirmed human WNV infection cases have been reportede (there were five cases in the last update), of these:

- twenty-three were West Nile Neuroinvasive Disease (WNND): 2 in Piedmont, 2 in Veneto, 1 Emilia-Romagna, 15 Latium, 3 Campania),

- one asymptomatic case was detected in a blood donor (Veneto),

- six cases of West Nile Fever have been reported (2 in Veneto, 4 Latium), and two asymptomatic cases (Latium),

- among the cases, there were two fatalities (1 in Piedmont, 1 in Latium).

-- The first confirmed case of the season was detected in Piedmont Region on March 20 2025 (sporadic case), then in Novara Province (July 3rd).

-- No confirmed cases of Usutu Virus infection have been detected so far.

(...)

Source: Istituto Zooprofilattico Sperimentale di Teramo, https://westnile.izs.it/j6_wnd/home

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#USA, #Wastewater #Data for Avian #Influenza #H5 (US CDC, July 25 '25)

 

{Excerpt}

Time Period: July 13, 2025 - July 19, 2025

-- H5 Detection: 2 sites (0.5%)

-- No Detection: 380 sites (99.5%)

-- No samples in last week: 47 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/nwss/rv/wwd-h5.html

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HKU5 #bat #merbecoviruses engage bat and #mink #ACE2 as entry #receptors

Abstract

Identifying receptors for bat coronaviruses is critical for spillover risk assessment, countermeasure development, and pandemic preparedness. While Middle East respiratory syndrome coronavirus (MERS-CoV) uses DPP4 for entry, the receptors of many MERS-related betacoronaviruses remain unknown. The bat merbecovirus HKU5 was previously shown to have an entry restriction in human cells. Using both pseudotyped and full-length virus, we show that HKU5 uses Pipistrellus abramus bat ACE2 but not human ACE2 or DPP4 as a receptor. Cryo-electron microscopy analysis of the virus-receptor complex and structure-guided mutagenesis reveal a spike and ACE2 interaction that is distinct from other ACE2-using coronaviruses. MERS-CoV vaccine sera poorly neutralize HKU5 informing pan-merbecovirus vaccine design. Notably, HKU5 can also engage American mink and stoat ACE2, revealing mustelids as potential intermediate hosts. These findings highlight the versatility of merbecovirus receptor use and underscore the need for continued surveillance of bat and mustelid species.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61583-7

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Controlling avian #influenza #spillover #events: a modelling study

Abstract

Avian influenza is a highly contagious viral disease that affects both domestic and wild birds, with occasional spillover to mammals, including humans. As of June 2025, 117 H5N1 infections in humans have been reported worldwide since 2020. Given the ability of the virus to infect mammals, there is a growing concern about its potential for human-to-human transmission. Currently, contact tracing and self-isolation are used in the UK to manage contacts of confirmed human cases of avian influenza. In this study, we aimed to estimate potential outbreak sizes and evaluate the effectiveness of contact tracing and self-isolation in managing avian influenza spillover events. We used a novel dataset from the Avian Contact Study to analyse contact patterns within an agricultural population at high risk of avian influenza exposure through contact with birds. We modelled outbreak sizes using a stochastic branching process model with measured contact data. Most simulations resulted in small-scale outbreaks, ranging from 0 to 10 cases. When the basic reproduction number was 1.1, contact tracing and self-isolation reduced the average outbreak size from 41 cases (95% Confidence Interval (CI): 37-46 cases) to 7 cases (95% CI: 6-8 cases), preventing, on average, 8 out of every 10 infections. However, they became less effective in reducing the outbreak size when a higher proportion of cases were asymptomatic. Overall, our findings suggest that contact tracing and self-isolation can be effective at preventing zoonotic infections. Increasing awareness, encouraging self-isolation, and detecting asymptomatic cases through routine surveillance are important components of zoonotic infection containment strategies.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Funding for the Avian Contact Study was awarded by PolicyBristol from the Research England QR Policy Support Fund (QR PSF) 2022-24 for investigating Zoonotic spillover of avian influenza. AT is funded by the Wellcome Trust, Early Career Award [227041/Z/23/Z]. EBP and IA acknowledge support from the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Evaluation and Behavioural Science at the University of Bristol (NIHR207385).

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.22.25331905v1

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#Rabies - #Timor-Leste (#WHO D.O.N., July 24 '25)

 

{Summary}

Situation at a glance

On 17 May 2025, the Timor-Leste government reported to the World Health Organization (WHO) a fatal human case of rabies from Ermera Municipality. 

Between May and mid-June 2025, Timor-Leste confirmed four human rabies deaths in the municipalities of Bobonaro (n=2), Ermera (n=1) and Oecusse (n=1). 

All cases involved individuals exposed to dogs' bites months prior to symptom onset, with rabies virus confirmed via Reverse Transcription Polymerase Chain Reaction (RT-PCR) testing. 

Since March 2024, a total of 106 animal rabies cases—mostly in dogs—have been reported, and over 1400 dog bites or scratches have occurred, with a total of six fatalities. 

Access to and completion of post-exposure prophylaxis remains limited. 

The spread of rabies into non-border areas like Ermera signals a growing public health concern. 

The public health response is ongoing and includes vaccination of dogs, risk communication, training of healthcare workers on Post-Exposure Prophylaxis (PEP) and case management, active surveillance, and ensuring the availability of rabies vaccines and human rabies immunoglobulin. 

Based on the current available information, the WHO assesses the risk posed by this event as high at the national level, moderate at the regional level, and low at the global level.

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON576

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The role of #ducks in detecting Highly Pathogenic Avian #Influenza in small-scale #backyard poultry #farms

Abstract

Previous research efforts on highly pathogenic H5N1 avian influenza (HPAI) suggest that different avian species exhibit a varied severity of clinical signs after infection. Waterfowl, such as ducks or geese, can be asymptomatic and act as silent carriers of H5N1, making detection harder and increasing the risk of further transmission, potentially leading to significant economic losses. For backyard hobby farmers, passive reporting is a common HPAI detection strategy. We aim to quantify the effectiveness of this strategy by simulating the spread of H5N1 in a mixed-species, small-population backyard flock. Quantities such as detection time and undetected burden of infection in various scenarios are compared. Our results indicate that the presence of ducks can lead to a higher risk of an outbreak and a higher burden of infection. If most ducks within a flock are resistant to H5N1, detection can be significantly delayed. We find that within-flock infection dynamics can heavily depend on the species composition in backyard farms. Ducks, in particular, can pose a higher risk of transmission within a flock or between flocks. Our findings can help inform surveillance and intervention strategies at the flock and local levels.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.23.666292v1

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#France - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

By Bengt Nyman from Vaxholm, Sweden - Larus canus 2203, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=49877446

Wild birds {Herring Gulls} found dead through SAGIR network.

Source: WOAH, https://wahis.woah.org/#/in-review/6672

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Hunting-training #dogs & companion dogs in #Netherlands are frequently exposed to highly pathogenic avian #influenza #H5 & human #H1N1 virus, 2021–2023

Highlights

• High seropositivity in dogs to highly pathogenic avian influenza (HPAI) H5 virus in the Netherlands during HPAI H5 endemicity in wild birds.

• HPAI H5-seropositivity higher in hunting-training dogs than companion dogs. 

• HPAI H5-seropositivity in hunting-training dogs associated with recent bird contact in/near water.

• High seropositivity in dogs to human H1N1pdm2009 influenza A virus (IAV).

• H1N1pdm2009-seropositivity higher in companion dogs than hunting-training dogs.

Abstract

Dogs are susceptible to the currently circulating highly pathogenic avian influenza (HPAI) H5 and human H1N1pdm2009 (pandemic H1N1) viruses, yet little is known about the extent to which dogs are exposed to both these viruses. Here we investigated HPAI H5 and human H1N1pdm2009 virus exposure in domestic dogs–including dogs that participated in hunting-training–and investigated lifestyle factors associated with HPAI H5 virus exposure. We screened sera from 538 dogs, sampled between 2021 and 2023, for influenza A virus antibodies, using ELISA and hemagglutination inhibition assays (HAIs). We analyzed lung tissue and (naso)pharyngeal swabs for influenza A viruses using RT-qPCR. Seropositivity to HPAI H5 virus was more frequent (13.3 %) in hunting-training dogs than in companion dogs with unknown bird contact (3.7 %). In contrast, seropositivity to H1N1pdm2009 was more frequent in companion dogs (7.1 %) than in hunting-training dogs (0.7 %). Based on owner questionnaires, seropositivity to HPAI H5 by ELISA in hunting-training dogs was significantly associated with recent bird contact in/near water (odds ratio 6.9). No influenza A viruses were detected in 207 necropsy dogs and 180 (hunting) dogs. Our findings suggest that dogs are frequently exposed to zoonotic influenza A viruses, and we recommend dog owners to avoid dog contact with sick/dead birds.

Source: OneHealth, https://www.sciencedirect.com/science/article/pii/S2352771425001703?via%3Dihub

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Long-term #efficacy of an inactivated #H5N1 whole-particle #influenza #vaccine in nonhuman #primates

Abstract

Outbreaks of H5 highly pathogenic avian influenza A viruses (HPAIVs) in animals pose a threat to humans immunologically naïve to avian influenza viruses. However, annual vaccination, such as for seasonal influenza is not planned because the number of human patients infected with H5 HPAIVs is small, and the possibility of human-to-human transmission of H5 HPAIVs is low at present. However, various clades of H5 HPAIVs have emerged continuously. Therefore, a vaccine that confers long-term and cross-clade immunity is required. To examine the long-term effectiveness and cross-clade reactivity of an H5 influenza virus vaccine, cynomolgus macaques were infected with an H5N1 HPAIV 5 years after two subcutaneous vaccinations with inactivated H5N1 whole-virus particles (H5 clade classical/outlier), which showed higher immunogenicity than did split vaccines in our previous studies. Neutralization titers against the vaccine strain were maintained for 5 years, and a recall immune response was observed on challenge infection against the challenge strain (clade 1) and other H5N1 HPAIV strains (clades 2.2, 2.3.2.1, and 2.3.4.4b). Compared with unvaccinated macaques, viral titers were low, and the cytokine signaling pathways related to the pathogenesis of an influenza virus infection were not activated in the vaccinated macaques. Thus, a whole-virus particle vaccine induced long-term memory sufficient to prevent severe pneumonia caused by an H5N1 HPAIV in cynomolgus macaques.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01221-x

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Preexisting #immunity to the 2009 pandemic #H1N1 virus reduces susceptibility to #H5N1 #infection and disease in #ferrets

Editor’s summary

The vast majority of the human population has immunity to influenza A virus (IAV) by prior infection, vaccination, or both. However, protection is generally subtype-specific, and it is not clear whether prior infection against one subtype could confer protection against clade 2.3.4.4b H5N1 IAVs, which are currently circulating in birds and dairy cows. Here, Restori et al. demonstrated that prior infection with the 2009 pandemic H1N1 IAV was protective against subsequent direct infection with H5N1 IAV in ferrets. Moreover, prior immunity reduced susceptibility to infection by transmission from an infected donor ferret. These data suggest that prior immunity to IAV, especially to the 2009 pandemic H1N1 virus, may offer a degree of protection against H5N1 infection. —Courtney Malo

Abstract

Zoonotic infections with emerging influenza viruses occur in the context of population-wide immunity to seasonal strains. Because of the worldwide spread of highly pathogenic clade 2.3.4.4b H5N1 influenza viruses in wild birds, there have been numerous spillover events into mammals. This includes a recent spillover into dairy cows that started an ongoing outbreak across the United States. Human infections with avian and bovine origin H5N1 influenza viruses have been documented, raising concern that these viruses may cause a pandemic. Therefore, using a ferret model, we evaluated the impact of preexisting, infection-elicited immunity on susceptibility to H5N1 infection and on severity of disease. Preexisting immunity to the 2009 pandemic H1N1 influenza virus prevented severe H5N1 disease and reduced susceptibility to infection through direct contact with an infected donor ferret. These studies demonstrate that preexisting immunity to influenza viruses, especially the 2009 pandemic H1N1 virus, is a barrier to infection and disease caused by clade 2.3.4.4b H5N1 viruses.

Source: Science Translational Medicine, https://www.science.org/doi/10.1126/scitranslmed.adw4856

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Chapter One - #Mucosal #Sudan virus #infection results in a lethal disease in #ferrets with previous #Lloviu virus infection not providing cross-protection

Abstract

Sudan virus (SUDV) causes highly lethal outbreaks of hemorrhagic disease throughout Africa, but there has yet to be an approved vaccine or therapeutic to combat this public health threat. The most common route of natural exposure to filoviruses is through mucosal contact which greatly impacts initial viral replication. Historically, SUDV animal models used an intramuscular infection route. Here, we sought to further characterize an animal model using mucosal challenge routes and compared the impact that intramuscular, intranasal, or aerosol exposure had on SUDV pathogenicity in a ferret model. We determined that the route of infection did not significantly impact overall SUDV pathogenicity; only subtle changes were detected in magnitude of viremia and oral viral shedding. Additionally, we sought to determine if preexisting Lloviu virus (LLOV) immunity could protect ferrets from lethal SUDV infection. We found that the previous immunity elicited by LLOV infection was not sufficient to protect ferrets from lethal SUDV disease. In conclusion, our results indicate that the infection route has minimal effect on overall pathogenicity of SUDV in ferrets and that prior LLOV infection does not elicit a cross-protective immune response to SUDV.

Source: Advances in Virus Research, https://www.sciencedirect.com/science/article/abs/pii/S0065352725000077?via%3Dihub

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The Winners Take It All? Evolutionary #Success of #H5Nx #Reassortants in the 2020–2024 #Panzootic

Abstract

Avian influenza viruses undergo frequent genetic reassortment, which can coincide with phenotypic changes in transmission, pathogenicity, and host species niche. Since 2020, clade 2.3.4.4b H5 high pathogenicity avian influenza viruses (HPAIVs) have driven a global panzootic, causing mass mortality in wild birds, poultry, and, for the first time, repeated spillover infections in a variety of mammalian species. This resurgence of H5 HPAIV has coincided with a dramatic increase in the number of circulating reassortant strains; however, the scale, impact and drivers of these reassortants remain unknown. Here, we combined statistical and phylodynamic modelling to reconstruct the global evolutionary dynamics of H5Nx viruses across four epizootic seasons (2020-2024). We identified 209 genetically distinct reassortants, stratified into three transmission categories based on their phylogenetic and epidemiological profiles. Accounting for sampling depth and HPAIV incidence, we estimated that reassortants emerged most frequently in Asia, but `major' reassortants associated with increased host range, inter-seasonal persistence, and long-range dissemination, more frequently emerged from Europe. Altogether, reassortant emergence followed an episodic pattern in which most reassortants were transient, but 3% seeded large clusters of secondary reassortants soon after their own emergence. Statistical modelling revealed that reassortant success was strongly shaped by ecological factors, including circulation in specific wild bird orders and the ability to infect a wider range of host niches. Reassortant dispersal was linked to poultry trade intensity, particularly in North America. Collectively, our findings reveal reassortment dynamics in H5 HPAIVs and identify key virological and ecological drivers underpinning the emergence and global spread of successful reassortants. These insights support the importance of enhanced surveillance to track evolution of H5 HPAIV and identify traits relevant for consideration in pandemic risk assessment.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information 

Declared

Biotechnology and Biological Sciences Research Council, BB/V011286/1, BB/X006204/1, BB/X006166/1, BB/Y007271/1, BB/Y007298/1

Biotechnology and Biological Sciences Research Council - Institute Strategic Grants, BBS/E/RL/230002C, BBS/E/RL/230002D

Medical Research Council, MR/Y03368X/1

National Natural Science Foundation of China, https://ror.org/01h0zpd94, 32061123001, 32425053, 32200416

National Key Research and Development Program of China, 2023YFC2307500

European Union, 727922, 874850, 101094685, 101084171, 874735

Fonds National de la Recherche Scientifique, F.4515.22

Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, G098321N

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.19.665680v1

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Emergence of Clade Ib #Monkeypox Virus—Current State of #Evidence

Abstract

Mpox was first identified against the backdrop of the smallpox eradication campaign. Monkeypox virus (MPXV), the causative agent of mpox, has been maintained in animal reservoirs in the forested regions of West and Central Africa as 2 distinct clades; clade I has historically caused more severe infection in Central Africa than clade II, historically found in West Africa. However, rapid reemergence and spread of both MPXV clades through novel routes of transmission have challenged the known characteristics of mpox. We summarize mpox demographic distribution, clinical severity, and case-fatality rates attributed to genetically distinct MPXV subclades and focus on MPXV clade Ib, the more recently identified subclade. Broad worldwide assistance will be necessary to halt the spread of both MPXV clades within mpox endemic and nonendemic regions to prevent future outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/24-1551_article

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#Genome #integration of human #DNA #oncoviruses

ABSTRACT

Tumors of infectious origin globally represent 13%. Oncogenic DNA viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV) are responsible for approximately 60% of these tumors. These oncoviruses are extensively studied to understand their role in cancer development, particularly through viral genome integration into the host DNA. Retroviruses require integration mediated by viral integrase for persistence, whereas DNA oncoviruses do not need integration for replication; instead, integration occurs incidentally. This process often targets fragile sites in the human genome, causing structural rearrangements that disrupt genes, activate proto-oncogenes, and increase genomic instability, all contributing to tumorigenesis. Integration near promoter regions and active genes is closely linked to carcinogenesis, highlighting its importance in developing diagnostic and therapeutic strategies. This review summarizes viral integration’s role in oncogenesis, mechanisms of integration, and methods to study this process, focusing on DNA tumor viruses such as HBV, EBV, HPV, and Merkel cell polyomavirus.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00562-25?af=R

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