Virus Infection Research Articles

Ubiquitination and degradation of MHC-II by Tim-3 inhibits antiviral immunity

We previously reported that Tim-3, an immune checkpoint inhibitor, inhibits MHC-II expression, but the molecular mechanisms involved and the implications for antiviral immunity remain to be determined. Here, we found that during H1N1 infection, Tim-3 inhibits MHC-II expression in macrophages/microglia in vitro. Tim-3 interacts with MHC-II via its intracellular tail and induces proteasomal dependent degradation of MHC-II. In H1N1 infected macrophages/microglia, Tim-3 promotes the K48-linked ubiquitination of MHC-II via MARCH8, a ubiquitin E3 ligase that can be upregulated by Tim-3. In H1N1 infected mice, specific knockout of Tim-3 in macrophages leads to a decreased viral load, attenuates tissue damage and increases the survival rate. We have thus identified a novel mechanism by which Tim-3 mediates virus immune escape. Manipulating the Tim-3-MHC-II signaling pathway may provide a novel treatment for viral infections.

What is the spectrum of kidney pathology associated with COVID-19?

Kidney involvement occurs in almost one third of patients hospitalised with coronavirus disease 2019 (COVID-19) and is associated with increased disease severity. This review aims to outline the spectrum of kidney pathology involved in COVID-19. Literature was reviewed systematically on the databases Medline OVID and Scopus in search of case reports, case series, cohort studies and autopsy studies of patients with COVID-19 who underwent kidney biopsies. Studies were published between August 2020 and November 2021. Fourteen studies consisting of 159 patients were included in this review. Acute tubular necrosis is the most common pathology followed by collapsing glomerulopathy, occurring in 40.1% and 28.9% of patients respectively. Of the 46 patients with collapsing glomerulopathy, 44 were of African descent with high-risk apolipoprotein L1 genotypes. Less common glomerular diseases include membranous nephropathy, secondary focal segmental glomerulosclerosis, minimal change disease and primary focal segmental glomerulosclerosis occurring in 5%, 4.4%, 3.1% and 2.5% of patients respectively. Glomerulonephritis occurred in a minority of patients. Direct viral infection has not been found as a definitive aetiology. Acute kidney injury occurs frequently in hospitalised COVID-19 patients and is associated with increased morbidity and mortality. The mechanisms underpinning acute kidney injury are multifactorial. Acute tubular necrosis is the most common. Collapsing glomerulopathy is the most common glomerular injury and is strongly linked to apolipoprotein L1 genotypes. Improved understanding of COVID-19-related kidney pathologies can guide treatment to improve patient outcomes and reduce progression of chronic kidney disease. The longitudinal impact of COVID-19-related kidney disease requires further research.

Changes in Epidemics of Respiratory Viral Infections Resulted From the COVID‐19 Pandemic in Shanghai

ABSTRACTTo investigate the changing patterns of respiratory viral infections within the context of COVID‐19 pandemic. The etiological surveillance data of eight respiratory viral pathogens among patients with ARIs in Shanghai between 2013 and 2023 were analyzed to evaluate the dynamic patterns of respiratory viral infections in Shanghai compared to global other regions during pre‐pandemic (period 1), pandemic (period 2), and post‐pandemic (period 3) periods of COVID‐19. In Shanghai and various other global regions, there was a delay of 2‒4 months in the peak positive rate of IFV and a reverse seasonality for RSV, HMPV, and HBoV was observed following the relaxation of NPIs. The proportion of patients infected with any of these eight viruses experiencing fever or high fever notably increased. During the entire study period, IFV was consistently identified as the most prevalent virus, with IFV‐B as the predominant stain during period 2, and IFV‐A regained its dominance following the lifting of NPIs. The proportion of RSV among children significantly increased during period 2 compared to period 1. With the relaxation of NPIs, there has been a resurgence of certain viral pathogens, accompanied by notable alterations in seasonal patterns and the spectrum of viral pathogens.

NK cell membrane/MnO2 hybrid nanoparticle-adjuvanted intranasal vaccines synergistically boost protective immunity against H1N1 influenza infection

Intranasal vaccines hold a huge promise for preventing influenza infection, however, their development is compromised due to mucosal barriers and limited systemic and mucosal immunity. Herein, a novel biomimetic nano-adjuvant based on NK cell membrane (MNK)/MnO2 hybrid nanoparticles (NLipoMn) was developed for intranasal administration of H1N1 inactivated influenza vaccine (IIV). NK cell membrane, served as TLR4 agonist was fused with cationic liposomes encapsulating STING agonist MnO2 NPs (LipoMn) to yield NLipoMn, which inherited versatile characteristics to prolong the nasal retention of IIV. Encouragingly, CCL20 secretion was enhanced by NLipoMn-activated the TLR4/NF-κB pathway in mucosal endothelial cells, thereby promoting submucosal dendritic cells (DCs) recruitment for IIV uptake. Moreover, NLipoMn-IIV synergistically harnessed TLR4 and STING signaling pathway to augment STING activation though NLipoMn-activated the TLR4/NF-κB pathway, which demonstrated a superiority to elicit strong DCs maturation, CD8+ T cells activation, and high levels of antigen-specific IgG, antigen-specific IgA, cytokines secretion, resulting in a robust systemic and mucosal immune responses. Notably, intranasal immunization with NLipoMn-IIV elicited an effective immune protection against homologous and heterologous H1N1 influenza virus infection. This study provides a promising adjuvant candidate to develop needle-free intranasal vaccines that are active against influenza and other respiratory viral infection.

EIF2Bβ confers resistance to Turnip mosaic virus by recruiting ALKBH9B to modify viral RNA methylation.

Eukaryotic translation initiation factors (eIFs) are the primary targets for overcoming RNA virus resistance in plants. In a previous study, we mapped a BjeIF2Bβ from Brassica juncea representing a new class of plant virus resistance genes associated with resistance to Turnip mosaic virus (TuMV). However, the mechanism underlying eIF2Bβ-mediated virus resistance remains unclear. In this study, we discovered that the natural variation of BjeIF2Bβ in the allopolyploid B. juncea was inherited from one of its ancestors, B. rapa. By editing of eIF2Bβ, we were able to confer resistance to TuMV in B. juncea and in its sister species of B. napus. Additionally, we identified an N6-methyladenosine (m6A) demethylation factor, BjALKBH9B, for interaction with BjeIF2Bβ, where BjALKBH9B co-localized with both BjeIF2Bβ and TuMV. Furthermore, BjeIF2Bβ recruits BjALKBH9B to modify the m6A status of TuMV viral coat protein RNA, which lacks the ALKB homologue in its genomic RNA, thereby affecting viral infection. Our findings have applications for improving virus resistance in the Brassicaceae family through natural variation or genome editing of the eIF2Bβ. Moreover, we uncovered a non-canonical translational control of viral mRNA in the host plant.

Hyperglycemia-triggered lipid peroxidation destabilizes STAT4 and impairs anti-viral Th1 responses in type 2 diabetes.

Patients with type 2 diabetes (T2D) are more susceptible to severe respiratory viral infections, but the underlying mechanisms remain elusive. Here, we show that patients with T2D and coronavirus disease 2019 (COVID-19) infections, and influenza-infected T2D mice, exhibit defective T helper 1 (Th1) responses, which are an essential component of anti-viral immunity. This defect stems from intrinsic metabolic perturbations in CD4+ Tcells driven by hyperglycemia. Mechanistically, hyperglycemia triggers mitochondrial dysfunction and excessive fatty acid synthesis, leading to elevated oxidative stress and aberrant lipid accumulation within CD4+ Tcells. These abnormalities promote lipid peroxidation (LPO), which drives carbonylation of signal transducer and activator of transcription 4 (STAT4), a crucial Th1-lineage-determining factor. Carbonylated STAT4 undergoes rapid degradation, causing reduced T-bet induction and diminished Th1 differentiation. LPO scavenger ameliorates Th1 defects in patients with T2D who have poor glycemic control and restores viral control in T2D mice. Thus, this hyperglycemia-LPO-STAT4 axis underpins reduced Th1 activity in T2D hosts, with important implications for managing T2D-related viral complications.

Risk Factors for Cytomegalovirus Infection after Haematopoietic Stem Cell Transplantation: A Meta-Analysis.

Cytomegalovirus (CMV) infection is the most common viral infection after haematopoietic stem cell transplantation (HSCT). However, studies on related risk factors give different views without any clear conclusion. Therefore, the purpose of this study was to evaluate the risk variables of CMV infection after HSCT in order to provide recommendations for therapeutic treatment. The National Knowledge Infrastructure [CNKI], Chinese Biomedical Literature database [SinoMed], Wanfang Digital Periodicals [WANFANG] and China Science and Technology Journal [VIP] databases, as well as PubMed, Embase, CENTRAL, Web of Science databases were searched. The search keyword was Cumulative Index of Nursing and Related Health Literature (CINAHL). The search time spanned from the time when the database was created to February 2023. Based on inclusion and exclusion criteria, two researchers independently chose the literature, retrieved data, and assessed the bias risk. The methodological quality of the included studies was assessed by the Newcastle Ottawa scale (NOS). A total of 1,038 literatures were retrieved, of which, 18 studies were finally included. The final results of meta-analysis showed that there were seven risk factors as follows: Acute graft-versus-host disease (aGVHD) grades II-IV (II-IV) [odds ratio = 3.39, 95% CI (2.13, 5.41), p <0.05]; ant-thymocyte globulin (ATG) administration in treatment [odds ratio = 2.53, 95% CI (1.41, 4.53), p <0.05]; cyclosporine level after transplantation (>300 ng/ml) [OR = 3.79, 95% CI (1.24, 11.65), p <0.05]; age [odds ratio = 1.83, 95% CI (1.06, 3.15), p <0.05]; neutrophil deficiency time [odds ratio = 6.58, 95% CI (2.24, 19.30), p <0.05]; CMV infection in recipients before transplantation [odds ratio = 6.32,95% CI (4.03, 9.90), p <0.05]; fungal infection [odds ratio = 2.63, 95% CI (1.09, 6.34), p <0.05]. This study preliminarily revealed that CMV infection after HSCT is related to aGVHD (II-IV), ATG administration in pretreatment, cyclosporine level (>300 ng/ml) after transplantation, age, neutrophil deficiency time, CMV infection in recipients before transplantation and fungal infection. However, the mechanisms behind the risk variables are unclear. Further research is necessary to understand the risk factors and to enhance the care of patients with these risk factors to prevent or control infection. Key Words: Haematopoietic stem cell transplantation, Cytomegalovirus infection, Risk factors, Meta-analysis.

Targeting the Ubiquitin Proteasome System to Combat Influenza A Virus: Hijacking the Cleanup Crew

ABSTRACTInfluenza A virus (IAV) remains a significant global public health threat, causing substantial illness and economic burden. Despite existing antiviral drugs, the emergence of resistant strains necessitates alternative therapeutic strategies. This review explores the complex interplay between the ubiquitin proteasome system (UPS) and IAV pathogenesis. We discuss how IAV manipulates the UPS to promote its lifecycle, while also highlighting how host cells utilise the UPS to counteract viral infection. Recent research on deubiquitinases as potential regulators of IAV infection is also addressed. By elucidating the multifaceted role of the UPS in IAV pathogenesis, this review aims to identify potential targets for novel therapeutic interventions.

Association of Herpes simplex infection with significantly increased risk of head and neck cancer: real-world evidence of about 500,000 patients.

The role of viral agents in the development of head and neck cancers has remained controversial. While markers of viral origin have been isolated from oral cancer tissues, a causative relationship has yet to be shown. The aim of this study was to evaluate the relationship between head and neck cancers and Herpes simplex virus, one of the most common viral infections of the oral orifice. Here, we conducted a retrospective analysis of two age- and gender-matched cohorts extracted from the real-world database TriNetX on March 10th, 2023, each consisting of 249,272 patients with and without Herpes simplex infections (ICD-10: B00). The diagnoses C00-C14 were analyzed, and risk analysis and Kaplan-Meier survival statics were computed. The strongest association was found for lip cancer (ICD-10: C00) with a hazard ratio [HR (CI 95% low-high)] of 3.08 (1.77-5.35). A significant association with HR of 1.17 (1.02-1.34) was found for the entire group of head and neck cancers. Confounders like smoking and alcohol dependence were considered using propensity score matching. The surprisingly strong correlation with lip, oral cavity, and pharynx neoplasms sheds new light on supposedly harmless herpes simplex infections, suggesting them as a possible new factor for risk stratification.

Real-World Assessment of Economic and Clinical Outcomes in Thai Patients With Respiratory Syncytial Virus Infection Across Age Groups: A Retrospective Cohort Analysis.

Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory infections worldwide, including Thailand. This study aimed to assess clinical and economic burdens of RSV infections across different age groups in Thailand. A retrospective cohort study was conducted using data from a tertiary care hospital from 2014 to 2021. Patients who tested at least one positive RSV were included and stratified into five age groups (< 2, 2-5, 5-18, 18-65, and > 65 years). Healthcare resource utilization, direct medical costs, and clinical outcomes were analyzed with descriptive statistics. Generalized linear models with gamma distributions and log link were used to model cost outcomes. Costs were reported in 2021 US dollars (USD), with 1 USD = 31.98 Thai Baht. A total of 2122 RSV-positive patients were identified, half of which (1097) were hospitalized. The median (interquartile range [IQR]) total hospitalization costs ranged from USD780 (IQR: USD488-USD1185) in those < 2 years to USD2231 (IQR: USD1250-USD4989) in those aged 65+ years. Case fatality rates among hospitalized patients also varied from 2.5% to 28.4% depending on age. Increased age, presence of comorbidities, and need for critical care were associated with higher hospitalization costs. Among RSV-positive patients, younger children experienced the greatest burden, but poorer outcomes were observed in older adults. Higher costs were associated with older age, comorbidities and critical care needs. Understanding RSV economic burdens is crucial for assessing the cost-effectiveness and public health value of vaccination programs that prioritize at-risk groups to mitigate the public health impact.

Rapid Decision Algorithm for Patient Triage during Ebola Outbreaks.

The low specificity of Ebola virus disease clinical signs increases the risk for nosocomial transmission to patients and healthcare workers during outbreaks. Reducing this risk requires identifying patients with a high likelihood of Ebola virus infection. Analyses of retrospective data from patients suspected of having Ebola virus infection identified 13 strong predictors and time from disease onset as constituents of a prediction score for Ebola virus disease. We also noted 4 highly predictive variables that could distinguish patients at high risk for infection, independent of their scores. External validation of this algorithm on retrospective data revealed the probability of infection continuously increased with the score.

Ocular manifestations of West Nile virus.

Over the past two decades, the ophthalmic manifestations of West Nile virus have been more clearly established in the literature. This review aims to summarize its diagnosis and pathogenesis, with a focus on its clinical appearance, characteristic imaging features, and management. Ocular manifestations of West Nile virus present early in the disease course and are more common in cases with severe neurological involvement. The use of optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), fundus autofluorescence (FAF), fluorescein angiogram (FA), and indocyanine green angiography (ICGA) can aid in its diagnosis and management. West Nile virus infection may present with ocular findings that include anterior uveitis, vitritis, retinitis, chorioretinitis, and optic neuropathy; visual prognosis can range from excellent to poor depending on severity of involvement and the presence of secondary complications, such as occlusive vasculitis and macular ischemia. Diagnosis may be aided by multimodal imaging assessment. The ophthalmologist should have a high clinical suspicion for ocular involvement in cases of severe systemic disease.

Non-pharmaceutical interventions to reduce influenza transmission in households: a systematic review and meta-analysis

Influenza pandemic plans often recommend non-pharmaceutical interventions (NPIs) in household settings, including hand hygiene and face masks. We reviewed the evidence supporting the recommendations of these measures to prevent the spread of influenza in households. We performed systematic reviews between 26 May and 30 August 2022 in Medline, PubMed, EMBASE, and CENTRAL to identify evidence for the effectiveness of selected measures recommended by representative national influenza pandemic plans. We prioritized evidence from randomized controlled trials conducted during influenza pandemics and seasonal influenza epidemics. Fixed-effects models were used to estimate the overall effects. Systematic reviews were registered in the OSF registry (https://osf.io/8kyth). We selected 9 NPIs for evidence review. We identified 9 randomized-controlled trials related to hand hygiene and face masks in household settings. 2 studies reported that measures could delay the introduction of influenza virus infections into households. However, we did not identify evidence from randomized controlled trials that indicated a substantial effect of hand hygiene and face masks in preventing the spread of influenza within households. Limited evidence indicated that within-household measures may likely be effective only when implemented before or as soon as possible after symptom onset in an infected case. Improving the evidence base for NPIs in households and elsewhere is a continuing priority. World Health Organization and the Strategic Topic Grants Scheme.

Predictors of Fertility Desire During COVID-19 Pandemic: A Cross Sectional Study

Background: Fertility, the most important factor in population growth, is affected by various factors, including pandemics. COVID-19 (CV) was a global challenge that spread rapidly around the world. Objective: This study aimed to investigate predictors of fertility desire during the covid virus pandemic. Methods: In this cross-sectional study, 315 women who visited health centers in northern Iran for vaccination against covid virus were recruited using convenient sampling. The participants completed the sociodemographic information, Fertility Desire Scale, and Fear of covid virus scale. Logistic regression analysis was employed to assess the predictive factors of fertility desire. Results: The participants' mean age and marriage duration were 34.4 ± 6.7, and 7.3±11.5 years, respectively. It showed fertility desire among household women was about twofold more compared to employed ones [Odds Ratio (OR) = 1.96, p = 0.009)]. The fertility desire was decreased among more educated women (OR = 0.43, p= 0.035), women with one child (OR = 0.44, p= 0.030), and women with no infant gender preferences (OR = 0.53, p= 0.032). Fear of covid virus and any history of covid virus infection in the participants or their close relatives did not change fertility desire (P &gt; 0.05). Conclusion: In conclusion, health policymakers should pay more attention to the potential effects of women's employment, their educational status, and their attitude toward infant gender preferences on fertility desire during the development of programs. Further research is needed to examine this empirical association on a global scale and its effect on trying to conceive.

Experimental West Nile virus infection provides lessons for recovery from enteric neuropathies.

Loss of enteric neurons leading to long-term gastrointestinal dysfunction is common to many diseases, and the path to functional recovery is unclear. In this issue of the JCI, Janova et al. report that West Nile virus killed enteric neurons and glia via CD4+ and CD8+ T cells acting through the perforin and Fas ligand pathways. Enteric glial cells contributed to neurogenesis and at least partial replacement of affected neurons. While neurogenesis is important for recovery, dysmotility and disruptions to the network structure persisted. Following enteric injury, the contribution of neurogenesis and the conditions that support restoration of enteric neural circuits for functional recovery remain for further investigation.

Endemic area of emerging tick-borne Yezo virus infections discovered in China

Endemic area of emerging tick-borne Yezo virus infections discovered in China

Low detection of H5N1 virus in commercial chickens with a low-level of vaccination coverage against H5N1 virus infection in Bangladesh

BackgroundBangladesh has reported > 560 H5N1 outbreaks in poultry and eight human cases since 2007. Commercial chicken farms were mostly affected. Commercial chicken farms across the country use imported vaccines against H5N1 virus; however, these vaccines did not use local circulatory isolates of H5N1virus. Vaccination may have limited effectiveness in chicken because of the mismatch in terms of subtypes and clades. To test this, we conducted a mixed-method study to assess the impact of ongoing vaccination against H5N1 virus on H5N1 viral shedding through freshly dropped feces of chickens raised in commercial farms that exclusively vaccinated or did not vaccinate their chickens.MethodsInitially, we collected vaccination coverage data from all active farms in a subdistrict of each of eight division. In each district, 25 vaccinated and 25 non-vaccinated chicken farms were selected randomly for sample collection. All samples were tested to detect avian influenza viruses using rRT-PCR.ResultsA total of 5092 poultry farms were surveyed; among them 1284 (25%) chicken farms administered vaccine against H5N1 virus. In total 21 of 400 tested farms (5%) had chicken feces samples that tested positive for AIVs; of these three were positive for H5N1 subtype of clade 2.3.2.1. Out of three H5N1 positive farms, 1 (33%) was vaccinated and 2 (67%) were unvaccinated. The chicken farms that administered vaccine against H5N1 was found protective for the detection of H5N1 viral RNA (aOR 0.39, 95% CI: 0.32–0.48). The H5N1 isolates of clade 2.3.2.1 sequenced in this study formed a cluster with the vaccine strain A/duck/Guangdong/S1322/2010 (H5N1) [Re-6].ConclusionsThe overall low vaccination coverage with low detection of H5N1 virus in commercial chickens makes it difficult to assess the effectiveness of the vaccine in reducing H5N1 viral shedding.

Oropouche Virus Infection: Differential Clinical Outcomes and Emerging Global Concerns of Vertical Transmission and Fatal Cases

Oropouche virus (OROV), a member of the Peribunyaviridae family, has emerged as a significant arboviral threat, particularly in South and Central America. Traditionally causing mild febrile illness, recent outbreaks have revealed severe clinical outcomes, including aseptic meningitis, encephalitis, and, more recently, vertical transmission leading to congenital anomalies and fatalities. Environmental changes, including deforestation and climate shifts, have expanded the virus's geographic range, as seen in Brazil, where over 8,000 cases were reported by August 2024, compared to fewer than 831in 2023. For the first time, vertical transmission has been confirmed, with cases of fetal deaths and congenital anomalies such as microcephaly and agenesis of the corpus callosum, drawing parallels to the Zika virus outbreak in 2015–2016. Despite these alarming trends, key mechanisms of placental transmission, maternal immunity, and fetal susceptibility remain poorly understood. This perspective highlights the urgent need for a coordinated global response, focusing on enhanced surveillance in newly affected regions, vector control strategies, and research into the factors driving severe clinical outcomes. Strengthening global efforts will be crucial in mitigating the public health threat posed by OROV, particularly in light of its potential for further geographic expansion and severe clinical manifestations.

Impact of CCR5Δ32 on the risk of infection, Staphylococcus aureus carriage, and plasma concentrations of chemokines in Danish blood donors

The CC chemokine receptor 5 (CCR5) is a suggested receptor for Staphylococcus aureus leukotoxin ED. Homozygosity for the Δ32 deletion (CCR5Δ32) protects against human immunodeficiency virus infection and possibly also against leukotoxin ED. We examined the impact of CCR5Δ32 on the susceptibility to S.aureus infection, all-cause infections, and S.aureus nasal carriage, respectively, and on the concentrations of circulating chemokines in blood donors. We included 95,406 participants from the Danish Blood Donor Study (DBDS) genotyped for >650,000 single nucleotide polymorphisms. The CCR5Δ32 (rs333, MAF: 0.12) was imputed from a reference panel and validated. Infectious outcomes were identified by diagnosis codes and redeemed prescription of antibiotics in national health registers. Data on S.aureus nasal carriage and forty-seven inflammatory biomarkers were available for 6721 and 7811 participants, respectively. Cox, logistic, and linear regression models adjusted for relevant confounders were used to explore said associations. During more than 700,000 person-years of observation, we found that CCR5Δ32 was associated with neither an increased risk of redeemed dicloxacillin, hospital-treated S.aureus-associated infection (replicated in 345,996 Icelanders), redeemed antibiotics, all-cause infection, and nor with S.aureus nasal carriage. We discovered an association between CCR5Δ32 and elevated CCL4 concentrations, which were 1.26-fold higher in Δ32-heterozygotes (95%-CI: 1.23-1.30) and 2.64-fold higher in Δ32-homozygotes (95%-CI: 2.41-2.90) compared with wildtype homozygotes. Conversely, concentrations of CCL2, CXCL-10, and CCL11 were slightly lower among Δ32-heterozygotes. Results from this CCR5Δ32 high-prevalent cohort do not support the idea that CCR5Δ32 affects the risk of S.aureus carriage or infection to any relevant degree, in this northern European context. CCL4 was the main chemokine affected by CCR5Δ32 and was observed in higher concentration among Δ32-carriers. This study cannot rule out that S.aureus is a previous driver of CCR5Δ32 selection. The Health Research Fund of Central Denmark Region, Aarhus University, Danish Administrative Regions, Bio- and Genome Bank Denmark, Danish Blood Donor Research Foundation, Aase & Ejnar Danielsens Foundation, Højmosegård Grant, National Institute of Allergy and Infectious Diseases, and A.P. Møller Foundation for the Advancement of Medical Science.

Inno4Vac Workshop Report Part 1: Controlled Human Influenza Virus Infection Model (CHIVIM) Strain Selection and Immune Assays for CHIVIM Studies, November 2021, MHRA, UK.

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including the development of CHIMs for influenza, respiratory syncytial virus and Clostridioides difficile. This report (in two parts) summarises a workshop held at the MHRA in 2021, focused on how to select CHIM candidate strains of influenza and respiratory syncytial virus (RSV) based on desirable virus characteristics and which immune assays would provide relevant information for assessing pre-existing and post-infection immune responses and defining correlates of protection. This manuscript (Part 1) summarises presentations and discussions centred around influenza CHIMs and immune assays (a second manuscript summarises RSV CHIM and immune assays: Inno4Vac workshop report Part 2: RSV CHIM strain selection and immune assays for RSV CHIM studies, November 2021, MHRA, UK).