Long-term serial passaging of #SARS-CoV-2 reveals #signatures of convergent #evolution

ABSTRACT

Understanding viral evolutionary dynamics is crucial to pandemic responses, prediction of virus adaptation over time, and virus surveillance for public health strategies. Whole-genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has enabled fine-grained studies of virus evolution in the human population. Serial passaging in vitro offers a complementary controlled environment to investigate the emergence and persistence of genetic variants that may confer selective advantage. In this study, nine virus lineages, including four “variants of concern” and three former “variants under investigation,” were sampled over ≥33 serial passages (range 33–100) in Vero E6 cells. WGS was used to examine virus evolutionary dynamics and identify key mutations with implications for fitness and/or transmissibility. Viruses accumulated mutations regularly during serial passaging. Many low-frequency variants were lost, but others became fixed, suggesting either in vitro benefits or at least a lack of deleterious effect. Mutations arose convergently both across passage lines and when compared with contemporaneous SARS-CoV-2 clinical sequences. These mutations included some that are hypothesized to drive lineage success through host immune evasion (e.g., S:A67V, S:H655Y). The appearance of these mutations in vitro suggested key mutations can arise convergently even in the absence of a multicellular host immune response through mechanisms other than immune-driven mutation. Such mutations may provide other benefits to the viruses in vitro, or arise stochastically. Our quantitative investigation into SARS-CoV-2 evolutionary dynamics spans the greatest number of serial passages to date and will inform measures to reduce the effects of SARS-CoV-2 infection on the human population.

IMPORTANCE

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a challenge for long-term public health efforts to minimize the effects of coronavirus disease 2019. Whole-genome sequencing of outbreak cases has enabled global contact tracing efforts and the identification of mutations of concern within the virus’ genome. However, complementary approaches are necessary to inform our understanding of virus evolution and clinical outcomes. Here, we charted the evolution of the virus within a controlled cell culture environment, focusing on nine different virus lineages. Our approach demonstrates how SARS-CoV-2 continues to evolve readily in vitro, with changes mirroring those seen in outbreak cases globally. Findings of the study are important for (i) investigating the mechanisms of how mutations arise, (ii) predicting the future evolutionary trajectory of SARS-CoV-2, and (iii) informing treatment and prevention design.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00363-25?af=R

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#Japan - #Influenza A #H5N2 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 A wild Peregrine falcon in Kagoshima Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6545

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Multiple introductions of #equine #influenza virus into the #UK resulted in widespread #outbreaks and #lineage #replacement

Abstract

Influenza A viruses (IAVs) are prime examples of emerging viruses in humans and animals. IAV circulation in domestic animals poses a pandemic risk as it provides new opportunities for zoonotic infections. The recent emergence of H5N1 IAV in cows and subsequent spread over multiple states within the USA, together with reports of spillover infections in humans, cats and mice highlight this issue. The horse is a domestic animal in which an avian-origin IAV lineage has been circulating for >60 years. In 2018/19, a Florida Clade 1 (FC1) virus triggered one of the largest epizootics recorded in the UK, which led to the replacement of the Equine Influenza Virus (EIV) Florida Clade 2 (FC2) lineage that had been circulating in the country since 2003. We integrated geographical, epidemiological, and virus genetic data to determine the virological and ecological factors leading to this epizootic. By combining newly-sequenced EIV complete genomes derived from UK outbreaks with existing genomic and epidemiological information, we reconstructed the nationwide viral spread and analysed the global evolution of EIV. We show that there was a single EIV FC1 introduction from the USA into Europe, and multiple independent virus introductions from Europe to the UK. At the UK level, three English regions (East, West Midlands, and North-West) were the main sources of virus during the epizootic, and the number of affected premises together with the number of horses in the local area were found as key predictors of viral spread within the country. At the global level, phylogeographic analysis evidenced a source-sink model for intercontinental EIV migration, with a source population evolving in the USA and directly or indirectly seeding viral lineages into sink populations in other continents. Our results provide insight on the underlying factors that influence IAV spread in domestic animals.

Author summary

Influenza causes significant disease burden in animals, including wild birds, sea lions, pigs, horses, dogs, and more recently, cows. Outbreaks and epizootics of influenza in agricultural species are a threat to food security and the economy whereas in wild animals they could affect biodiversity and conservation efforts. Given the zoonotic nature of influenza viruses and the high levels of contact between domestic animals and humans, animal influenza is also a public health concern. Here, we combined geographical, epidemiological, and virus sequence data to determine key factors that led to one of the largest epizootics of equine influenza in the United Kingdom in decades. We show that an American equine influenza virus lineage was introduced into Europe and replaced the virus lineage that had been circulating in the United Kingdom for nearly 20 years. We also analysed a global dataset of virus genomes and propose a model of equine influenza virus intercontinental migration, in which USA is the main source of viruses to other countries. Our results provide important information concerning the basic principles of influenza virus circulation in animal populations. This is central to devise effective measures of disease control that would increase animal health while reducing zoonotic risk.

Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013227

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4th #meeting of #IHR (2005) Emergency #Committee regarding upsurge of #mpox 2024 – Temporary #recommendations (#WHO, June 9 '25)

Fourth meeting of the International Health Regulations (2005) Emergency Committee regarding the upsurge of mpox 2024 – Temporary recommendations

The Director-General of the World Health Organization (WHO), following the fourth meeting of the International Health Regulations (2005) (IHR) Emergency Committee regarding the upsurge of mpox 2024, held on 5 June 2025, from 12:00 to 17:00 CEST, concurs with its advice that the event continues to meet the criteria of a public health emergency of international concern and, considering the advice of the Committee, he is hereby issuing a revised set of temporary recommendations.

The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee. The proceeding of the fourth meeting of the Committee will be shared with States Parties to the IHR and published in the coming days.

Temporary recommendations

These temporary recommendations are issued to States Parties experiencing the transmission of monkeypox virus (MPXV), including, but not limited to, those where there is sustained community transmission, and where there are clusters of cases or sporadic travel-related cases of MPXV clade Ib.

They are intended to be implemented by those States Parties in addition to the current standing recommendations for mpox, valid until 20 August 2025.

In the context of the global efforts to prevent and control the spread of mpox disease outlined in the WHO Strategic framework for enhancing prevention and control of mpox: 2024–2027, the aforementioned standing recommendations apply to all States Parties.

All current WHO interim technical guidance can be accessed on this page of the WHO website. WHO evidence-based guidance has been and will continue to be updated in line with the evolving situation, updated scientific evidence, and WHO risk assessment to support States Parties in the implementation of the WHO Strategic Framework for enhancing mpox prevention and control.

Pursuant to Article 3 Principle of the International Health Regulations (2005) (IHR), the implementation of these temporary recommendations, as well as of the standing recommendations for mpox, by States Parties shall be with full respect for the dignity, human rights and fundamental freedoms of persons, in line with the principles set out in Article 3 of the IHR.

Note: The text in backets next to each temporary recommendation indicates the status with respect to the set of temporary recommendations issued on 27 November 2024.

Emergency coordination

-- Secure political commitment and engagement to intensify mpox prevention and response efforts, including resource allocation, for the lowest administrative and operational level reporting mpox cases (hotspots) in the prior 4 weeks. (EXTENDED)

-- Establish or enhance national and local emergency prevention and response coordination arrangements as recommended in the WHO Mpox global strategic preparedness and response plan (2025), and its upcoming iteration, and in line with the WHO Strategic framework for enhancing prevention and control of mpox: 2024–2027. (EXTENDED, with updated reference)

-- Establish or enhance coordination among all partners and stakeholders engaged in or supporting mpox prevention and response activities through cooperation, including by introducing accountability mechanisms. (EXTENDED)

-- Establish a mechanism to monitor the effectiveness of mpox prevention and response measures implemented at lower administrative levels, so that such measures can be adjusted as needed. (EXTENDED)

-- Engage with and strengthen partner organizations for collaboration and support for mpox response, including humanitarian actors in contexts with insecurity, humanitarian corridors, or areas with internal or refugee population displacements and in hosting communities in insecure areas. (EXTENDED, with re-phrasing)

Collaborative surveillance

-- Enhance mpox surveillance, by increasing the sensitivity of the approaches adopted and ensuring comprehensive geographic coverage. (EXTENDED)

-- Expand access to accurate, affordable and available diagnostics to test for mpox, including through strengthening arrangements for the transport of samples, the decentralization of testing and arrangements to differentiate MPXV clades and conduct genomic sequencing. (EXTENDED)

-- Identify, monitor and support the contacts of persons with suspected, clinically-diagnosed or laboratory-confirmed mpox to prevent onward transmission. (EXTENDED)

-- Scale up efforts to thoroughly investigate cases and outbreaks of mpox to better understand the modes of transmission and transmission risk, and prevent its onward transmission to contacts and communities. (EXTENDED)

-- Report to WHO suspected, probable and confirmed cases of mpox in a timely manner and on a weekly basis. (EXTENDED)

Safe and scalable clinical care

-- Provide clinical, nutritional and psychosocial support for patients with mpox, including, where appropriate and possible, isolation in care centres and/or access to materials and guidance for home-based care. (EXTENDED)

-- Develop and implement a plan to expand access to optimized supportive clinical care for all patients with mpox, including children, pregnant women, and persons living with HIV, recognising the association of mpox-related morbidity and mortality in persons living with HIV with untreated or advanced HIV. This includes prompt identification and effective management of endemic co-infections, such as malaria, chickenpox or measles. This also includes offering HIV tests to adult patients who do not know their HIV status and to children as appropriate, testing and treatment for other sexually transmitted infections (STIs) among cases linked to sexual contact and referral to HIV/STIs treatment and care services when indicated. (EXTENDED, with re-phrasing)

-- Strengthen health and care workers’ capacity, knowledge and skills in clinical and infection and prevention and control pathways – screening, diagnosis, isolation, environmental cleaning, discharge of patients, including post discharge follow up for suspected and confirmed mpox –, and provide health and care workers with personal protective equipment (PPE). (EXTENDED)

-- Strengthen adherence to infection prevention and control (IPC) measures and availability of water, sanitation, hygiene (WASH) and waste management services and infrastructure in healthcare facilities and treatment and care centers to ensure quality healthcare service delivery and protection of health and care workers, caregivers and patients. (EXTENDED, with re-phrasing)

International traffic

-- Establish or strengthen cross-border collaboration arrangements for surveillance, management and support of suspected cases and contacts of mpox, and for the provision of information to travellers and conveyance operators, without resorting to travel and trade restrictions that unnecessarily impact local, regional or national economies. (EXTENDED)

Vaccination

-- Continue to prepare for and implement targeted use of vaccine for “Phase 1-Stop the outbreak” (as defined in the WHO Mpox global strategic preparedness and response plan (2025)) through the identification of the lowest administrative level reporting cases (hotspots) and targeting those groups at high risk of mpox exposure to interrupt sustained community transmission. (EXTENDED, with rephrasing and updated reference)

-- Develop and implement plans for vaccination in the context of an integrated response at the lowest administrative level reporting cases for people at high risk of exposure (e.g., contacts of cases of all ages, health and frontline workers, and other groups at risk such as those with multiple sexual partners and sex workers in endemic and non-endemic areas). This entails a targeted integrated response, including active surveillance and contact tracing; agile adaptation of immunization strategies and plans to the local context including dose-sparing options (single dose/fractional dosing) in the context of limited availability of vaccines; proactive community engagement to generate and sustain demand for and trust in vaccination; close monitoring of mpox vaccination activities, coverage and adverse events following immunization (AEFI); assessment of vaccine effectiveness; and documenting lessons learned and their implementation. (MODIFIED)

Community protection

-- Strengthen risk communication and community engagement in affected communities and local workforces for outbreak prevention, response and vaccination strategies, particularly at the lowest administrative levels reporting cases. Key actions include training, mapping high risk and vulnerable populations for tailored interventions, data driven approaches for social listening, community feedback and dialogue, and managing misinformation. This entails, inter alia, communicating effectively the uncertainties and new information regarding the natural history of mpox and modes of transmission, the effectiveness of mpox vaccines and duration of protection following vaccination, and about any clinical trials to which the local population may have access, as appropriate. (EXTENDED, with re-phrasing)

-- Address stigma and discrimination of any kind via meaningful community engagement, particularly in health services and during risk communication activities, and through engagement with civil society groups, such as HIV networks. (EXTENDED, with re-phrasing)

-- Promote and implement IPC measures and basic WASH and waste management services in household settings, congregate settings (e.g. prisons, internally displaced persons and refugee camps, etc.), schools, points of entry and cross border transit areas. (EXTENDED)

Governance and financing

-- Galvanize and scale up national funding and explore external opportunities for targeted funding of mpox prevention, readiness and response activities, advocate for release of available funds and take steps to identify potential new funding partners for emergency response. (EXTENDED)

-- Optimize the use of resources, in the context of global and local external funding shortfalls, by allocating available resources to the implementation of core mpox response interventions needed in the medium term; maximizing their cost-efficiency through cross-programmatic synergetic approaches; and by engaging partners in resource-sharing arrangements to maintain the delivery of essential health services. (NEW)

-- Integrate mpox prevention and response measures, including enhanced surveillance, in existing programmes for prevention, control and treatment of other endemic diseases – especially HIV, as well as STIs, malaria, tuberculosis and other vaccine-preventable diseases, and/or non-communicable diseases – striving to identify activities which will benefit the programmes involved and lead to better health outcomes overall. (EXTENDED)

Addressing research gaps

-- Invest in addressing outstanding knowledge gaps and in generating evidence, during and after outbreaks, as defined in A coordinated research roadmap – Mpox virus - Immediate research next steps to contribute to control the outbreak (2024), including for vaccine effectiveness in different contexts. (EXTENDED, with re-phrasing)

-- Invest in field studies to better understand animal hosts and zoonotic spillover in the areas where MPXV is circulating, in coordination with the animal health sector and One Health partners. (EXTENDED)

-- Strengthen and expand use of genomic sequencing to characterize the epidemiology and chains of transmission of MPXV to better inform control measures, particularly regarding the emergence and circulation of new virus strains. (EXTENDED, with re-phrasing)

Reporting on the implementation of temporary recommendations

-- Report quarterly to WHO on the status of, and challenges related to, the implementation of these temporary recommendations, using a revised standardized tool and channels that will be made available by WHO, also allowing for the monitoring of progress and the identification of gaps of the national response. (EXTENDED, with re-phrasing)

___

Source: World Health Organization, https://www.who.int/news/item/09-06-2025-fourth-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-upsurge-of-mpox-2024-temporary-recommendations

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E627V #mutation in #PB2 protein promotes the #mammalian #adaptation of novel #H10N3 avian #influenza virus

Abstract

Since 2021, the novel H10N3 has caused four cases of human infection in China, the most recent of which occurred in December 2024, posing a potential threat to public health. Our previous studies indicated that several avian H10N3 strains are highly pathogenic in mice and can be transmitted between mammals via respiratory droplets without prior adaptation. By analyzing the genome sequence, we found that these H10N3 viruses carry the PB2-E627V mutation, which is becoming increasingly common in several subtypes of avian influenza viruses (AIV); however, its mechanism in mammalian adaptation remains unclear. Using a reverse genetics system, we investigated the role of PB2-E627V in the adaptation of H10N3 to mammals and poultry. Our findings demonstrate that the PB2-E627V mutation is critical for the high pathogenicity of novel H10N3 in mice and its ability to be transmitted through the air among mammals. Additionally, we found that the role of PB2-627 V in promoting AIV adaptation to mammals is comparable to that of PB2-627 K. More importantly, PB2-627 V appears to be equally suited to long-term persistence in poultry. Therefore, using PB2-627 V as a novel molecular marker to assess the epidemic potential of AIV is of great significance for preventing possible influenza pandemics in the future.

Source: Veterinary Research, https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-025-01534-8

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Death of Actaeon, Titian (1559 - 1575)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/titian/death-of-actaeon-1562

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42. RAMIREZ-SOTO MC, Arroyo-Hernandez H
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43. NOPKUESUK N, Klamrak A, Nabnueangsap J, Narkpuk J, et al
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44. CHAN R, Brady B, Zou J, McMullan M, et al
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45. YAN H, Hu S, Zhang H, Zhou Y, et al
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46. BRAESEMANN F, Kluge J, Lorenz H
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47. VILLAR J, Macaira P, Baiao FA
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48. MBOGORI E, Thiongo K, Deng HY, Gikunyu CW, et al
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49. KIM J, Lee S, Weir P
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50. WANG Z, Jin Y, Tian W, Zhou X, et al
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51. EID R, Sayad A, Samaan W, Salameh P, et al
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52. KOSTINOV M, Svitich O, Chuchalin A, Gajnitdinova V, et al
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History of Mass Transportation: The FS ALn 772 Autorail

 

By Kabelleger / David Gubler (http://www.bahnbilder.ch) -  http://www.bahnbilder.ch/pictures/medium/8253.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16836731

Source: Wikipedia, https://en.wikipedia.org/wiki/FS_Class_ALn_772

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Efficacy and safety of #onradivir in adults with acute uncomplicated #influenza A infection in #China ...

Summary

Background

Onradivir (ZSP1273) is a potent inhibitor of the PB2 subunit of influenza A virus (IAV) polymerase. Our previous, phase 2 clinical trial showed that a 600 mg regimen of onradivir initiated within 48 h of symptom onset can expedite the recovery of adult patients from acute, uncomplicated influenza. Here, we aimed to evaluate the safety and therapeutic efficacy of onradivir in a larger group with acute, uncomplicated influenza.

Methods

This randomised, double-blind, multicentre, placebo-controlled and oseltamivir-controlled, phase 3 trial was conducted at 68 clinical sites in China. Eligible participants were adults (aged 18–64 years) with an influenza-like illness who screened positive by rapid IAV antigen testing at the first clinical visit, and had a fever (axillary temperature ≥38·0°C) with at least one moderate systemic and one moderate respiratory symptom within 48 h of symptom onset. Patients were randomly assigned into three treatment groups, stratified by influenza symptom scores (≤11 or ≥12), in a 2:1:1 ratio by an interactive web response system, with each treatment lasting 5 days: 600 mg oral onradivir tablets once daily, 75 mg oral oseltamivir phosphate capsules twice daily, or oral placebo. The primary outcome was the efficacy of onradivir versus placebo in the time to alleviation of symptoms (TTAS), from treatment initiation to the remission of influenza symptoms, in the intention-to-treat infection (ITTI) population (ie, all participants who were randomly assigned and tested positive for IAV). The safety endpoints were the frequency and severity of adverse events in all participants who received treatment at least once. This trial is registered with ClinicalTrials.gov (NCT04683406) and is completed. This clinical trial was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (EC-2020-080[YW]-02).

Findings

Between May 12, 2022, and May 16, 2023, 943 patients were screened, of whom 750 met the inclusion criteria and were randomly assigned to a group. 48 had negative IAV tests, resulting in an ITTI population of 702 participants (413 [59%] men and 289 [41%] women; mean age 28·1 years [SD 9·7]): 349 in the onradivir group, 177 in the oseltamivir group, and 176 in the placebo group. The baseline viral load (mean 5·15 log10 copies per mL [SD 1·02]) and the total score of seven influenza symptoms at enrolment were similarly distributed among the groups. The median TTAS in the onradivir group was significantly shorter than that of placebo (38·83 h [95% CI 35·32–41·18] vs 63·35 h [55·48–68·48], difference –24·52 h, p<0·0001, HR 1·53 [95% CI 1·27–1·85]) and similar to that of the oseltamivir group (42·17 h [38·27–52·83], p=0·092, HR 1·12 [0·93–1·35]. Adverse events occurred in 250 (67%) of 373 in the onradivir group, 104 (55%) of 189 in the placebo group, and 89 (47%) of 188 in the oseltamivir group. Although the incidence of diarrhoea was higher in the onradivir group (184 [49%]) than in the placebo (44 [23%]) or oseltamivir (28 [15%]) groups, most incidences were grade 1 or 2, lasted a median of 2 days (IQR 1–3), and resolved without medication.

Interpretation

Onradivir has similar curative efficacy to oseltamivir for acute, uncomplicated influenza infections in adult patients, with an acceptable safety profile. At a time when reduced susceptibility to antiviral drugs is a growing concern, this study indicates that onradivir could be an alternative antiviral option or a candidate for use in combination with other antiviral agents for uncomplicated IAV infection.

Source: Lancet Respiratory Medicine, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(25)00046-3/abstract?rss=yes#au50

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#Virological characteristics of the #SARS-CoV-2 #NB181 #variant

{Excerpt}

After the spread of SARS-CoV-2 JN.1, its subvariants, such as KP.3 (JN.1.11.1.3)1 and KP.3.1.1 (JN.1.11.1.3.1.1),2 and XEC (a recombinant lineage of two JN.1 subvariants),3 emerged and rapidly spread globally. Subsequently, LP.8.1 (JN.1.11.1.1.1.3.8.1),4 a descendant lineage of KP.1.1.3 (JN.1.11.1.1.1.3), accounts for approximately 30% of all global infections as of April, 2025, as per data from Nextstrain. Thereafter, NB.1.8.1 (XDV.1.5.1.1.8.1), a descendant lineage of XDV, has started to spread worldwide. XDV is a recombinant lineage of XDE (a recombinant lineage of GW.5.1 [XBB.1.19.1.5.1] and FL.13.4 [XBB.1.9.1.13.4]) and JN.1. NB.1.8.1 has acquired seven spike substitutions and 23 non-spike substitutions compared with JN.1 (appendix pp 15–16). Compared with the XEC spike protein, the NB.1.8.1 spike bears four substitutions: G184S, K478I, A435S, and L1104V (appendix pp 15–16). We estimated the relative effective reproduction number (Re) of NB.1.8.1 using a Bayesian multinomial logistic model1–4 based on genome surveillance data from Singapore, Hong Kong, Australia, and the USA, where this variant has spread as of April, 2025 (appendix pp 9–13, 15–16). The Re of NB.1.8.1 was 1·17-fold higher than that of LP.8.1 in Singapore, suggesting its potential to outcompete the other major SARS-CoV-2 lineages (appendix pp 15–16).

(...)

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00356-1/fulltext?rss=yes

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Enhancing protective efficacy and immunogenicity of #hemagglutinin-based #influenza #vaccine utilizing adjuvants developed by BECC

Abstract

Seasonal influenza viruses continue to pose a significant threat, causing substantial morbidity and mortality in the US and worldwide despite the availability of vaccines and antivirals. These challenges may be addressed by improving vaccine immunogenicity through the inclusion of adjuvants that enhance immune responses against key antigens including influenza hemagglutinin (HA). BECC (Bacterial Enzymatic Combinatorial Chemistry) adjuvants are novel Toll-like Receptor 4 (TLR4) ligands created by modifying enzymes from lipid A synthesis pathways in Gram-negative bacteria. This study compares the ability of the biological and synthetic versions of these adjuvants to enhance the efficacy of recombinant HA (rHA) antigens in mouse influenza virus challenge. Mice immunized with rHA adjuvanted with BECCs stimulate the humoral and cell-mediated arms of the immune system without exhibiting cytotoxicity/pyrogenicity. A robust HA-specific immunoglobulin subtype, especially IgG2a, response was observed in mice adjuvanted with BECCs as compared to control adjuvants, MPL, and PHAD Further, animals adjuvanted with BECC470 cleared infection seven days post-infection, demonstrating their potential for further translational development. Vaccination adjuvanted with BECCs were also able to increase immune recognition of linear B and T cell epitopes when compared to control adjuvants, as well as induce durable immune response eighteen months post-vaccination. Together, these findings indicate that BECCs may serve as highly effective adjuvants in influenza vaccination.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.03.657703v1

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#Influenza A virus #polymerase co-opts distinct sets of host proteins for #RNA transcription or #replication

Abstract

The influenza A virus polymerase, consisting of a heterotrimer of three viral proteins, carries out both transcription and replication of the viral RNA genome. These distinct activities are regulated by viral proteins that vary in abundance during infection, and by various co-opted host cell proteins, which serve as targets for the development of novel antiviral interventions. However, little is known about which host proteins direct transcription and which replication. In this report, we performed a differential interactome screen to identify host proteins co-opted as either transcription- or replication-specific factors. We found that distinct sets of host proteins interact with the influenza polymerase as it carries out the different activities. We functionally characterised HMGB2 and RUVBL2 as replication-specific cofactors and RPAP2 as a transcription-specific cofactor. Our data demonstrate that comparative proteomics can be used as a targeted approach to uncover virus-host interactions that regulate specific stages of the viral lifecycle.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.06.658254v1

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#USA, #Wastewater Data for Avian #Influenza A(#H5) (CDC, June 6 '25)

 

{Excerpt}

Time Period: May 25, 2025 - May 31, 2025

- H5 Detection: 10 sites (2.5%)

- No Detection: 389 sites (97.5%)

- No samples in last week: 52 sites

(...)

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

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#Antigenic and #virological characteristics of #SARS-CoV-2 #variants BA.3.2, #XFG, and #NB181

{Excerpt}

The SARS-CoV-2 saltation variant BA.3.2, harbouring over 50 mutations relative to its ancestral BA.3 lineage, has recently drawn global attention (figure A). Notably, BA.3.2 exhibits 44 mutations distinct from the currently dominant LP.8.1/LP.8.1.1 variant (appendix p 4), raising speculation about its potential to drive an outbreak similar to BA.2.86/JN.1, particularly following its first detection outside South Africa in the Netherlands on April 2, 2025.1–5 A critical evaluation of its antigenic profile and infectivity is essential to establish its likelihood of prevailing.

(...)

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00308-1/fulltext?rss=yes

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#Serological insights into #MERS-CoV dynamics of #antibody responses during acute and convalescent phases and their clinical relevance for #diagnostics and immunity

Abstract

Introduction

Middle East respiratory syndrome (MERS) is a zoonotic viral respiratory disease caused by the Middle East respiratory syndrome coronavirus (MERS-CoV), associated with severe clinical outcomes and high mortality.

Objectives

Our study examined the kinetics of anti-MERS-CoV IgM and IgG antibodies during the acute and convalescent phases of infection, focusing on their correlations with clinical variables such as age and viral load.

Methods

Serum samples were collected from PCR-confirmed MERS-CoV patients (n = 23) during both phases and compared to healthy controls (n = 23) using validated ELISA-based assays.

Results

IgM levels peaked in the acute phase and declined significantly in the convalescent phase, while IgG levels were sustained and markedly higher during recovery. Correlation analyses revealed positive relationships between antibody levels and patient age (acute IgM: r = 0.56, p < 0.01; convalescent IgG: r = 0.59, p < 0.01) and viral loads (acute IgM: r = 0.97, p < 0.0001; acute IgG: r = 0.87, p < 0.0001; convalescent IgG: r = 0.91, p < 0.0001). These results concluded that age-associated enhancements in antibody responses and the role of humoral immunity in viral clearance.

Conclusion

The current study highlights the diagnostic value of anti-MERS-CoV IgM and IgG measurements and their utility in developing therapeutic and vaccine strategies adapted to high-risk populations.

Source: Journal of Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034125002035?via%3Dihub

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