ETIDIOH - NEW

Abstract In the past two decades, two pandemic respiratory viruses (H1N1 and SARS-CoV-2) have emerged via spillover from animal reservoirs . In an effort to avert future pandemics, surveillance studies aimed at identifying zoonotic viruses at high risk of spilling over into humans act to monitor the `viral chatter' at the animal-human interface . These studies are hampered, however, by the diversity of zoonotic viruses and the limited tools available to assess pandemic risk. Methods currently in use include the characterization of candidate viruses using in vitro laboratory assays and experimental transmission studies in animal models . However, transmission experiments yield relatively low-resolution outputs that are not immediately translatable to projections of viral dynamics at the level of a host population. To address this gap, we present an analytical framework to extend the use of measurements from experimental transmission studies to generate more quantitative risk assessm...

Abstract Rationale and Objectives :  Iron availability and metabolism are important in the pathogenesis of bacterial infections . More recently, links have been reported between iron and the severity of viral infections . In this study, we characterize a crucial relationship between iron metabolism and IAV infection and disease.  Methods :  Iron-related gene expression was assessed in human airway epithelial cells (AEC) infected with IAV. AECs were cultured with ferric iron, iron-loaded transferrin, or iron chelator, deferoxamine (DFO), prior to infection with IAV. Mice were placed on a high iron diet for 8 weeks prior to infection with IAV or treated with anti-transferrin receptor-1 (TFR1) antibody during IAV infection. The effects of iron modulation and depletion of TFR1-mediated responses on IAV infection were assessed.  Measurements and main results :  Iron-related gene expression and metabolism are altered systemically and in lung tissues and AECs during IA...

Abstract Influenza virus neuraminidase (NA) is receiving increasing attention as a target for universal flu vaccines . Several broad NA inhibition monoclonal antibodies (BImAbs) targeting the highly conserved enzymatic pocket have been previously described. However, the molecular characteristics, clonal evolutionary trajectory, and B cell sources of BImAbs remain poorly understood. Here, using NA-mutant probes, we comprehensively profiled the immune signatures of NA-specific memory B cells (MBCs) from a healthy individual with NA cross-inhibition activity . From the NA-specific MBC repertoires, we identified a series of NA BImAbs with molecular features characterized by long HCDR3 regions with an xxxDRxxx motif, which exhibited broad inhibition against diverse influenza NAs. Clonal lineage tracing revealed that these BImAbs followed a clonal evolutionary trajectory encompassing classical MBC (cMBC) and atypical MBC (aMBC). Both cMBC- and aMBC-derived NA BImAbs displayed similar inhibit...

Abstract Influenza viruses are highly capable of mutating and adapting in mammalian hosts . While these viruses have been extensively studied in birds, research on their presence in bats has been limited. However, influenza viruses circulating in bats have shown notable molecular divergence . The present study aimed to characterize the phylogenetic, evolutionary, and antigenic relationships of an influenza A virus detected in the fishing bat Noctilio albiventris . As part of a pathogen surveillance study of public health interest, 159 rectal samples were collected from bats in the Colombian Caribbean . The samples were sequenced using RNA-Seq. A genome (eight viral contigs) associated with the Orthomyxoviridae family was identified in a pool. Most segments showed approximately 90% similarity with H18N11, except for the neuraminidase. Analysis of the N protein shows that occupies a basal position relative to the N11 subtype, with its divergence date estimated to be approximately 50 year...

Abstract We detected neutralizing antibodies, viral RNA, and sialic acid receptors for Alphainfluenzavirus influenzae in urban coatis (Nasua nasua) in Brazil , suggesting exposure and susceptibility. We used hemagglutination inhibition, reverse transcription qualitative PCR, and immunohistochemistry for detection. Increased epidemiologic wildlife surveillance would improve influenza A emergency event response. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/3/23-1640_article ____

Abstract Influenza A virus (IAV) non-canonical replication products can be bound by host pathogen sensors , such as retinoic acid-inducible gene I (RIG-I). However, innate immune activation is infrequent in cell culture infection, in particular by adapted strains. Moreover, it is not understood why non-canonical IAV RNAs activate RIG-I in a sequence- or RNA structure-dependent manner. We therefore hypothesized that multiple errors need to occur before influenza virus RNA synthesis activates innate immune signaling . To test this idea, we investigated whether RIG-I activation is stimulated by the non-canonical or aberrant transcription of mini viral RNAs (mvRNA), a <125 nt long RNA that is overexpressed in pandemic and highly pathogenic IAV infections . Using mvRNA sequences identified in tissue culture and ferret infections , we find that mvRNAs can cause non-canonical transcription termination through a truncated 5ʹ polyadenylation signal or a 5ʹ transient RNA structure that interr...

Abstract To better manage seasonal and pandemic influenza infections , new drugs are needed with enhanced activity against amantadine- and rimantadine-resistant influenza A virus (IAV) strains containing the S31N variant of the viral M2 ion channel (M2S31N). Here we tested 36 amantadine analogs against a panel of viruses containing either M2S31N or the parental, M2 S31 wild-type variant (M2WT). We found that several analogs, primarily those with sizeable lipophilic adducts, inhibited up to three M2S31N-containing viruses with activities at least 5-fold lower than rimantadine, without inhibiting M2S31N proton currents or modulating endosomal pH. While M2WT viruses in passaging studies rapidly gained resistance to these analogs through the established M2 mutations V27A and/or A30T, resistance development was markedly slower for M2S31N viruses and did not associate with additional M2 mutations. Instead, a subset of analogs, exemplified by 2-propyl-2-adamantanamine (38), but not 2-(1-adama...

Abstract Enveloped viruses such as influenza A virus (IAV) often produce a mixture of virion shapes , ranging from 100 nm spheres to micron-long filaments. Spherical virions use fewer resources, while filamentous virions resist cell-entry pressures such as antibodies . While shape changes are believed to require genetic adaptation , the mechanisms of how viral mutations alter shape remain unclear. Here we find that IAV dynamically adjusts its shape distribution in response to environmental pressures . We developed a quantitative flow virometry assay to measure the shape of viral particles under various infection conditions (such as multiplicity, replication inhibition and antibody treatment) while using different combinations of IAV strains and cell lines. We show that IAV rapidly tunes its shape distribution towards spheres under optimal conditions but favours filaments under attenuation . Our work demonstrates that this phenotypic flexibility allows IAV to rapidly respond to environm...

  BMC Pediatr KUDLACEK M, Fromel K, Groffik D, Mitas J, et al Individual physical activity preferences of adolescents in the Czech Republic and Poland: a 14-year comparative study reflecting the gender trends and prospective responses to global lifestyle challenges. BMC Pediatr. 2025;25:98. PubMed           Abstract available J Infect Dis GOYA S, Wendm ST, Xie H, Nguyen TV, et al Genomic Epidemiology and Evolution of Rhinovirus in Western Washington State, 2021-2022. J Infect Dis. 2025;231:e154-e164. PubMed           Abstract available CHIME N, Anspach B, Jain V, Laajalahti O, et al Phase 3 Study Assessing Lot-to-lot Consistency of RSVPreF3 Vaccine and its Immune Response, Safety, and Reactogenicity When Co-administered with FLU-D-QIV. J Infect Dis. 2024 Jul 5:jiae342. doi: 10.1093. PubMed           Abstract available BARZAGHI F, Visconti C, Pipiton...

{Excerpt} Novel Influenza A Virus Infections One human infection with influenza A(H1N2) variant (A(H1N2)v) virus was reported by the Iowa Department of Health and Human Services . The patient is ≥18 years of age and sought health care during the week ending January 18, 2025 (Week 3), was hospitalized , and has recovered from their illness.  An investigation by state public health officials did not identify direct or indirect swine contact by the patent.  No illness was identified among the patient's close contacts.  No human-to-human transmission has been identified associated with this case. This is the first human infection with a variant influenza virus reported during the 2024-2025 season in the United States. When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a "variant" influenza virus.  Most human infections with variant influenza viruses occur following exposure to swine, but human-to-human transmi...

Abstract Viral infections are characterized by dispersal from an initial site to secondary locations within the host. How the resultant spatial heterogeneity shapes within-host genetic diversity and viral evolutionary pathways is poorly understood. Here, we show that virus dispersal within and between the nasal cavity and trachea maintains diversity and is therefore conducive to adaptive evolution , whereas dispersal to the lungs gives rise to population heterogeneity . We infected ferrets either intranasally or by aerosol with a barcoded influenza A/California/07/2009 (H1N1) virus . At 1, 2, or 4 days postinfection, dispersal was assessed by collecting 52 samples from throughout the respiratory tract of each animal. Irrespective of inoculation route, barcode compositions across the nasal turbinates and trachea were similar and highly diverse, revealing little constraint on the establishment of infection in the nasal cavity and descent through the trachea. Conversely, infection of the ...

  Biochem Biophys Res Commun DU S, Yang L, Chen X, Chen Y, et al Engineering mRNA vaccine with broad-spectrum protection against SARS-cov-2 variants. Biochem Biophys Res Commun. 2025;746:151224. PubMed           Abstract available BMC Pediatr YANG SI, Choi CH, Lee EJ, Jee SH, et al Impact of pediatric COVID-19 isolation on children's well-being and caregiver mental health. BMC Pediatr. 2025;25:37. PubMed           Abstract available Epidemiol Infect NOSTAEVA A, Shimansky V, Apalko S, Kuznetsov I, et al Case-control association study between polygenic risk score and COVID-19 severity in a Russian population using low-pass genome sequencing. Epidemiol Infect. 2024;153:e13. PubMed           Abstract available J Infect RJOOB K, Antonelli M, Murray B, Molteni E, et al Symptom Evolution in Individuals with Ongoing Symptomatic COVID-19 and Post COVID-19 Sy...

ABSTRACT Respiratory and encephalitic virus infections represent a significant risk to public health globally . Detailed investigations of immunological responses and disease outcomes during sequential virus infections are rare. Here, we define the impact of influenza virus infection on a subsequent virus encephalitis . We used a model system in which mice were given influenza A virus (IAV) infection 8 days prior to Semliki Forest virus (SFV) infection (IAV→SFV). IAV infection clearly attenuated the subsequent SFV infection with reduced titers of infectious SFV and lower levels of cytokines and chemokines in the central nervous system ( CNS ). In contrast, the SFV viremia in both IAV→SFV and SFV-only mice was comparable. Increased type I interferon (IFN) levels in the CNS after IAV infection might have contributed to some level of protection towards SFV infection in the CNS, suggesting that early control of SFV replication in the CNS during IAV→SFV infection led to reduced adaptive res...

Abstract Crocodilians are susceptible to a range of virus infection including influenza A virus (IAV). However, little is known about the ecology and epidemiology of IAV in crocodile species. This study aimed to investigate IAV infection in farmed Siamese crocodiles in central Thailand . We collected plasma samples and pharyngeal swab samples from Siamese crocodiles residing in 13 crocodile farms in 9 provinces of central Thailand during 2019. Additional archival plasma samples of Siamese crocodiles collected in 2012 and 2018 were also included in the study. Plasma samples were screened for influenza A antibodies by a hemagglutination inhibition (HI) assay and positive were evaluated by a cytopathic effect/hemagglutination based- microneutralization (MN) assay . Swab samples were tested for influenza viral RNA by a real-time RT-PCR assay targeting the influenza matrix (M) gene. Among 246 tested plasma samples, the overall seroprevalence of antibodies against IAV in farmed Siamese croco...

Abstract Zoonotic infections (swine-human) caused by influenza A viruses (IAVs) have been reported and linked to close contact between these species . Here, we describe eight human IAV variant infections ( 6 mild and 2 severe cases , including 1 death ) detected in Paraná, Brazil , during 2020–2023. Genomes recovered were closely related to Brazilian swIAVs of three major lineages (1 A.3.3.2/ pdm09, 1B/human-like, and H3.1990.5), including three H1N1v, two H1N2v, two H3N2v and one H1v. Five H1v were closely related to pdm09 lineage , one H1v ( H1N2v ) grouped within 1B.2.3 clade, and the two H3v grouped within a clade composed exclusively of Brazilian H3 swIAV (clade H3.1990.5.1). Internal gene segments were closely related to H1N1pdm09 isolated from pigs . IAV variant rarely result in sustained transmission between people, however the potential to develop such ability is of concern and must not be underestimated. This study brings into focus the need for continuous influenza surveilla...

Highlights -- Both NA-specific antibodies and memory B cells are detected in healthy adults -- NA broad-inhibition monoclonal antibodies are derived from classical memory B cells -- Broad inhibition monoclonal antibodies target the NA conserved enzymatic epitopes -- NA broad-inhibition antibodies protect mice against H1N1 and H5N1- clade 2.3.4.4b Summary Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine . In this study, using influenza neuraminidase (NA) mutant probes , we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzym...

Natalia A. Ilyushina {a b}, Nicolai V. Bovin {c}, Robert G. Webster {a d}, Elena A. Govorkova  {a b} a} Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA; b} The D.I. Ivanovsky Institute of Virology, Gamaleya 16, Moscow 123098, Russia; c} Shemyakin Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia; d} Department of Pathology, University of Tennessee, Memphis, TN 38105, USA Received 21 November 2005, Accepted 26 January 2006, Available online 21 February 2006. Abstract Rapid development of resistant influenza variants after amantadine treatment is one of the main drawbacks of M2 blockers . On the other hand, the emergence of variants with low susceptibility to the neuraminidase (NA) inhibitors is limited. In the present study we examined whether combination therapy with two classes of anti-influenza drugs can affect the emergence of resistant variants in vitro. We observed that viru...

 {Excerpt} KINSHASA, Dec. 21 (Xinhua) -- The Democratic Republic of the Congo (DRC) is grappling with a deadly illness of unknown origin that has claimed dozens of lives in a province, prompting investigations and heightened alertness as test results are awaited. "This is, therefore, influenza, which has been formally identified," Patrick Muyaya, spokesperson for the DRC government, announced at a national television broadcast late Friday as he read the minutes of the Council of Ministers meeting chaired by President Felix Tshisekedi in Kinshasa, the country's capital, earlier that day. During the meeting, Public Health Minister Roger Kamba said that since October, 592 cases of the illness have been recorded in the Panzi health zone of the southwestern Kwango province . Symptoms exhibited by patients are "similar to the flu," according to Kamba, who noted that the outbreak coincides with the seasonal flu period, which peaks in December. Laboratory analysis revea...

Abstract Influenza A viruses (IAVs) initially infect a few host cells , and the infection subsequently spreads to neighboring cells . However, the molecular mechanisms underlying this expansion remain unclear. Here, we show that IAV infection upregulates the frequency of intercellular calcium wave propagations (iCWPs) that mediate the spread of IAVs. ADP released from initially infected cells mediated iCWPs via the P2Y1 receptor. The generation of iCWPs and spread of viral infection were inhibited by a P2Y1 antagonist. Enhanced endocytosis in the surrounding cells that received ADP signaling upregulated viral entry. Expression of IAV matrix protein 2 (M2) in initially infected cells triggered iCWPs through ADP diffusion, thereby increasing infection, whereas an ion permeability-deficient mutation of M2 or inhibition of its ion channel activity suppressed iCWPs. Therefore, intercellular calcium signaling is essential for early expansion and potential establishment of IAV infection, whic...

Abstract A historical perspective of more than one hundred years of influenza surveillance in New York State demonstrates the progression from anecdotes and case counts to next-generation sequencing and electronic database management, greatly improving pandemic preparedness and response . Here, we determined if influenza virologic surveillance at the New York State public health laboratory (NYS PHL) tests sufficient specimen numbers within preferred confidence limits to assess situational awareness and detect novel viruses that pose a pandemic risk. To this end, we analyzed retrospective electronic data on laboratory test results for the influenza seasons 1997–1998 to 2021–2022 according to sample sizes recommended in the Influenza Virologic Surveillance Right Size Roadmap issued by the Association of Public Health Laboratories and Centers for Disease Control and Prevention. Although data solely from specimens submitted to the NYS PHL were insufficient to meet surveillance goals, when ...