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| Open AccessTwo noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections
There are limited therapeutics available for treatment of mpox. In this study, the authors identify two non-competing human neutralizing monoclonal antibodies with protective effects against orthopoxvirus infection in a mouse model and structurally resolve the targeted epitope within the MPXV B6 protein.
- Runchu Zhao
- , Lili Wu
- & Qihui Wang
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Article
| Open AccessNanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles
The precise cellular localization of the SARS-CoV-2 RNA and replication partners has been elusive. Here, the authors use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscale structure of viral replication organelles.
- Leonid Andronov
- , Mengting Han
- & W. E. Moerner
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Article
| Open AccessUniversal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein
There is a lack of vaccines for prevention of human respirovirus 3 (RV3) infection. Bakkers et al. report the design of a stabilized RV3 preF protein vaccine candidate that induces strong neutralizing antibodies and protective responses in small animal models.
- Johannes P. M. Langedijk
- , Freek Cox
- & Mark J. G. Bakkers
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Article
| Open AccessCryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses
In this study the authors present the Thogoto virus polymerase cryo-EM structures and reveal unique RNA synthesis mechanisms among orthomyxoviruses. RNA synthesis by Thogoto virus polymerase is shown to be weakly dependent on the host factors ANP32A/B/E in human cells in contrast to influenza viruses.
- Lu Xue
- , Tiancai Chang
- & Xiaoli Xiong
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Article
| Open AccessStructural insights into the DNA topoisomerase II of the African swine fever virus
African swine fever virus is the sole mammalian-infecting virus encoding a type II topoisomerases (pP1192R). The authors present pP1192R structures in different states, illustrating the enzymatic mechanisms of viral type II topoisomerases.
- Jingyuan Cong
- , Yuhui Xin
- & Yutao Chen
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Article
| Open AccessThe low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells
This study shows that Crimean-Congo hemorrhagic fever virus (CCHFV) recruits apoE, an exchangeable apolipoprotein that mediates LDL/LDL-R interaction, to promote virion entry via the LDLR. Molecules that down-regulate LDL-R inhibit CCHFV infection.
- Maureen Ritter
- , Lola Canus
- & Solène Denolly
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Article
| Open AccessDeciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level
Here, Kessler et al use single-cell RNA sequencing of the intestine and mesentery from H18N11 influenza-infected bats to show that viral infection is predominant in leukocytes and causes activation of immune cells and antiviral gene signatures.
- Susanne Kessler
- , Bradly Burke
- & Kevin Ciminski
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Article
| Open AccessSafety outcomes following COVID-19 vaccination and infection in 5.1 million children in England
COVID-19 vaccines reduce the risk of severe disease in young people, but the absolute risk is low, and side effects have been reported. Here, the authors use data on 5–17 year olds in England to assess the overall risk-benefit profile of the vaccines.
- Emma Copland
- , Martina Patone
- & Julia Hippisley-Cox
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Article
| Open AccessLongitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study
Here the authors measure viral load in samples from skin lesions, saliva, oropharynx, and rectum of 77 patients with acute monkeypox virus infection as well as from environmental fomite swabs and show a high seropositivity rate for antibodies against A29L and H3L.
- Yang Yang
- , Shiyu Niu
- & Yingxia Liu
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Article
| Open AccessAcute and post-acute respiratory complications of SARS-CoV-2 infection: population-based cohort study in South Korea and Japan
Respiratory complications of SARS-CoV-2 infection have been described in the acute (within 30 days) and post-acute (after 30 days) phase. Here, the authors characterise the risk of acute and post-acute respiratory complications of SARS-CoV-2 using population-based data from South Korea and Japan.
- Yujin Choi
- , Hyeon Jin Kim
- & Dong Keon Yon
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Article
| Open AccessHuman neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head
Here the authors isolate two human antibodies, H7.HK1 and H7.HK2, that achieve broad and potent neutralization against H7N9 influenza by targeting a distinct lateral patch on the hemagglutinin head, thus making them favorable to complement other antibodies for combination therapy.
- Manxue Jia
- , Hanjun Zhao
- & Xueling Wu
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Article
| Open AccessProximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2
Type I IFN is vital for antiviral defense. Here, the authors use TurboID-based proximity labeling to comprehensively map the protein landscapes surrounding core IFN signaling members. Among factors uncovered, PJA2 emerged as a negative regulator of IFN signaling that ubiquitinates the Janus kinases.
- Samira Schiefer
- & Benjamin G. Hale
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Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
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Article
| Open AccessCompound mortality impacts from extreme temperatures and the COVID-19 pandemic
Extreme weather and pandemics are classified as two of the most serious risks facing the UK in its National Risk Register. Here, the authors investigate the compound mortality impacts of extreme high and low temperatures and COVID-19 in England and Wales.
- Y. T. Eunice Lo
- , Dann M. Mitchell
- & Antonio Gasparrini
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Article
| Open AccessPost-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection
The impact of COVID-19 vaccination on post-COVID conditions is not well understood. Here, the authors use electronic health record data from a network of eight integrated healthcare systems in the United States to compare rates of post-COVID conditions in those with and without vaccination.
- Debbie E. Malden
- , In-Lu Amy Liu
- & Sara Y. Tartof
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Article
| Open AccessA potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer
There are no approved interventions for Hendra or Nipah viruses. Here, the authors isolate a G glycoprotein-specific antibody with cross-neutralizing and in vivo protective activities, and structurally resolve its binding pattern to the G protein.
- Pengfei Fan
- , Mengmeng Sun
- & Sandra Chiu
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Article
| Open AccessDevelopment of a long noncoding RNA-based machine learning model to predict COVID-19 in-hospital mortality
Identifying biomarkers associated with risk of severe COVID-19 disease could inform clinical management. Here, the authors identify a long noncoding RNA associated with severe disease using data from three European countries, and validate their finding in data from Canada.
- Yvan Devaux
- , Lu Zhang
- & Hüseyin Firat
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Article
| Open AccessSpatial disparities in the mortality burden of the covid-19 pandemic across 569 European regions (2020-2021)
Excess mortality can be used as an indicator of the impacts of the COVID-19 pandemic. Here, the authors estimate excess mortality in 569 European regions in 25 countries for 2020 and 2021 and describe how impacts changed over time.
- Florian Bonnet
- , Pavel Grigoriev
- & Carlo-Giovanni Camarda
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Article
| Open AccessEnhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Multi-Inflammatory Syndrome in Children (MIS-C) is a severe post-infectious presentation related to SARS-CoV-2 infection. Here authors used multi-omics approaches to characterise MIS-C cases and found increased CD95 and IL-18 signalling accompanying the expansion of TCR Vβ 21.3+ T cells.
- Zhenguang Zhang
- , Iain R. L. Kean
- & Nazima Pathan
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Article
| Open AccessOriginal COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters
Waning immunity and the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness and required vaccine updates. Here, the authors assess how different priming regimens affect the immunogenicity of BA.1 and BA.5 bivalent boosters.
- Luca M. Zaeck
- , Ngoc H. Tan
- & Rory D. de Vries
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Article
| Open AccessVascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation
The molecular basis underlying infection infection-mediated lung pathology is not fully revealed. Here the authors report that SPARCL1 expressed in pulmonary capillary endothelial cells contributes to immune pathology in mouse model via pro-inflammatory macrophage induction, while circulating SPARCL1 levels corelate with COVID-19 lethality.
- Gan Zhao
- , Maria E. Gentile
- & Andrew E. Vaughan
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Article
| Open AccessStructural mechanism of bacteriophage lambda tail’s interaction with the bacterial receptor
Here, Ge et al use cryo-electron microscopy to resolve the structure of the bacteriophage lambda tail in complex with its LamB receptor from Shigella sonnei and shed light on the conformational changes that the phage tail fiber undergoes in response to binding.
- Xiaofei Ge
- & Jiawei Wang
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Article
| Open AccessStructures of the mumps virus polymerase complex via cryo-electron microscopy
The viral polymerase complex is crucial for both genome replication and transcription in non-segmented negative-strand RNA viruses. Here, the authors link varying structures of polymerase complexes with their dual functions and propose a sliding model for them to advance along the RNA templates.
- Tianhao Li
- , Mingdong Liu
- & Qing-Tao Shen
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Article
| Open AccessStructure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site
HIV relies on the RRE RNA interaction with Rev protein for nuclear export of viral mRNAs. The structure of the high-affinity Rev binding site in RRE in two conformations suggests a mechanism for initial Rev binding and oligomerization onto RRE.
- Jerricho Tipo
- , Keerthi Gottipati
- & Kyung H. Choi
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Article
| Open AccessImpacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years
Population mobility is associated with SARS-CoV-2 transmission but its impacts on other respiratory viruses are not well understood. Here, the authors investigate associations between mobile phone-derived mobility metrics and the dynamics of 18 respiratory viruses in Seattle, Washington from 2018 to 2022.
- Amanda C. Perofsky
- , Chelsea L. Hansen
- & Cécile Viboud
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Article
| Open AccessThe nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression
Here, Murray-Nerger et al use a genome-wide CRISPR/Cas9 screen to show that the nuclear protein SFPQ suppresses lytic reactivation of Epstein-Barr virus by promoting the expression and accumulation of linker histone H1 on the viral genome.
- Laura A. Murray-Nerger
- , Clarisel Lozano
- & Benjamin E. Gewurz
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Article
| Open AccessThe EV71 2A protease occupies the central cleft of SETD3 and disrupts SETD3-actin interaction
Enteroviruses are responsible for several human diseases without treatment. This study describes the molecular interactions between SETD3, actin, and viral 2A in viral replication, providing a framework for the development of host-targeted therapies against enteroviruses.
- Xiaopan Gao
- , Bei Wang
- & Sheng Cui
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Article
| Open AccessImportance of social inequalities to contact patterns, vaccine uptake, and epidemic dynamics
Contact patterns influence the spread of infectious diseases, but mathematical models of epidemics typically only account for age differences in contacts. Here, the authors investigate the importance of other sociodemographic characteristics in shaping contact patterns and vaccine uptake using survey data from Hungary.
- Adriana Manna
- , Júlia Koltai
- & Márton Karsai
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Article
| Open AccessSerological evidence of zoonotic filovirus exposure among bushmeat hunters in Guinea
In a serological analysis, Bore et al. utilise serum samples, collected from a cohort of individuals associated with bushmeat hunting and butchering, in the forested region of Guinea, a region close to the epicentre of the 2013–2016 West Africa Ebola virus disease epidemic.
- Joseph Akoi Boré
- , Joseph W. S. Timothy
- & Miles W. Carroll
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Article
| Open AccessADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection
Mice lacking A Disintegrin and Metalloproteinase 9 (ADAM9) do not mount Type 1 interferon responses against encephalomyocarditis infection. Here, Bazzone et al show that ADAM9 regulates innate immune responses via by MDA5.
- Lindsey E. Bazzone
- , Junji Zhu
- & Evelyn A. Kurt-Jones
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Article
| Open AccessSequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity
Here, the authors show that GalNAc-T3 and T7 regulate furin cleavage of the SARS-CoV-2 spike protein via O-glycosylation. This influences viral assembly and infection, highlighting glycosylation as a host defense mechanism.
- Shengjun Wang
- , Wei Ran
- & Yang Mao
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Article
| Open AccessRisk assessment of a highly pathogenic H5N1 influenza virus from mink
In 2023, a highly pathogenic H5N1 virus caused an outbreak in mink. In the ferret model of influenza, the virus exhibits limited airborne transmissibility and high virulence. These findings indicate heightened pandemic potential of these viruses.
- Katherine H. Restori
- , Kayla M. Septer
- & Troy C. Sutton
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Article
| Open AccessOctyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.
- Naziia Kurmasheva
- , Aida Said
- & David Olagnier
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Article
| Open AccessStructures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation
The authors demonstrate how avian H5N1 influenza A virus polymerase interacts with human ANP32B to facilitate the replication of the viral genetic information in mammalian hosts, revealing insights into cross-species transmission.
- Ecco Staller
- , Loïc Carrique
- & Ervin Fodor
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Article
| Open AccessFunctional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning
Deep mutational scanning experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 with different cell lines revealed that mutations at residue 813 of the spike protein reduced TMPRSS2-mediated entry with decreased virulence.
- Ruipeng Lei
- , Enya Qing
- & Lok-Yin Roy Wong
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Article
| Open AccessSafety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).
- Nhân Thị Hồ
- , Steven G. Hughes
- & Xuan-Hung Nguyen
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Article
| Open AccessGene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo
The main challenge for anti-HSV therapy is to target latent virus in ganglionic neurons. Here, the authors report a well-tolerated anti-HSV gene editing approach against HSV which targets latent HSV genomes and leads to reductions of ganglionic viral loads, and viral shedding upon reactivation in mouse models.
- Martine Aubert
- , Anoria K. Haick
- & Keith R. Jerome
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Article
| Open AccessRelationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes
Human leucocyte antigens are important in the adaptive immune response. Here, the authors use data from the UK Biobank linked to electronic health records to investigate the association between genetic variation in HLA alleles and antibody responses to SARS-CoV-2 vaccination and breakthrough COVID-19 outcomes.
- Junqing Xie
- , Beatriz Mothe
- & Daniel Prieto Alhambra
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Article
| Open AccessHerpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase
Encephalitis is a rare and severe complication of Herpes Simplex type 1 infection. Here, Bibert et al describe a genetic variant in a 2-year-old affected child that impairs interferon production in neuronal cells and enhances viral replication.
- Stéphanie Bibert
- , Mathieu Quinodoz
- & Pierre-Yves Bochud
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Article
| Open AccessTemporal shifts in 24 notifiable infectious diseases in China before and during the COVID-19 pandemic
Public health and social measures for COVID-19 also impacted the incidence of other infectious diseases. In this study, the authors characterise the impacts of these measures on 24 notifiable infectious diseases in China until December 2023.
- Kangguo Li
- , Jia Rui
- & Tianmu Chen
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Article
| Open AccessHigh SARS-CoV-2 incidence and asymptomatic fraction during Delta and Omicron BA.1 waves in The Gambia
Many low- and middle-income countries, including The Gambia, had low COVID-19 vaccination coverage during the emergence of the Delta and Omicron variants. Here, the authors perform a prospective household cohort study in the Gambia to investigate the dynamics of SARS-Cov-2 infection in this setting.
- Sheikh Jarju
- , Rhys D. Wenlock
- & Thushan I. de Silva
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Article
| Open AccessReplication competent HIV-guided CRISPR screen identifies antiviral factors including targets of the accessory protein Nef
Innate immune mechanisms are critical for antiviral defense. Here, the authors developed a CRISPR/Cas9-based HIV-driven approach to identify cellular factors compromising viral transcription, assembly, release or infectivity in human T cells. They identify targets of the Nef protein as antiviral factors.
- Caterina Prelli Bozzo
- , Alexandre Laliberté
- & Frank Kirchhoff
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Article
| Open AccessSeasonal antigenic prediction of influenza A H3N2 using machine learning
This study presents a machine learning model that accurately predicts seasonal antigenic changes of influenza A H3N2 using genetic data. The model’s predictions can aid influenza surveillance, vaccine strain selection, and public health management.
- Syed Awais W. Shah
- , Daniel P. Palomar
- & Matthew R. McKay
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Article
| Open AccessAdjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus
Here, Dillard and Taft-Benz et al. show in a female mouse model how different adjuvants affect inactivated vaccine-mediated protection against homologous SARS-CoV-2 and heterologous SARS-CoV-1-like coronaviruses. They find that an aluminum hydroxide-adjuvanted vaccine can increase risk of adverse outcomes during heterologous infection.
- Jacob A. Dillard
- , Sharon A. Taft-Benz
- & Mark T. Heise
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Article
| Open AccessConcomitant human papillomavirus (HPV) vaccination and screening for elimination of HPV and cervical cancer
Here the authors report baseline results of a population-based trial testing concomitant human papillomavirus (HPV) vaccination and HPV-based screening of young women in Sweden and, using a transmission model, suggest that this approach may reduce high-risk HPV infections.
- Laila Sara Arroyo Mühr
- , Andrea Gini
- & Joakim Dillner
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Article
| Open AccessDynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19
In this study, the authors report the case of a patient who underwent lung transplantation and subsequently developed COVID-19 that resulted in persistent infection. Following antiviral treatment, SARS-CoV-2 (BA.5) showed dynamic genetic diversity with remdesivir resistant mutations leading to enhanced fusogenicity.
- Hidetoshi Igari
- , Seiichiro Sakao
- & Eiji Ido
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Article
| Open AccessCD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age
Influenza B viruses are linked to significant morbidity and mortality, and yet their immunobiology is comparatively poorly understood. Here Menon et al identify influenza B virus-specific CD8+ T cell epitopes and characterise these in adults, children and the elderly.
- Tejas Menon
- , Patricia T. Illing
- & Katherine Kedzierska
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Article
| Open AccessHIV transmission dynamics and population-wide drug resistance in rural South Africa
There is limited data on drug resistance in South African communities strongly affected by HIV. In this study, the authors observed low levels of resistance to newer drugs but widespread resistance to older HIV medications in a South African community. Resistance to rilpivirine was detected even in untreated individuals.
- Steven A. Kemp
- , Kimia Kamelian
- & Ravindra K. Gupta
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Article
| Open AccessOxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3
Oxygen is an essential requirement for aerobic organisms. Here the authors explore the role of oxygen in the antiviral innate response in multiple models of infection and suggest oxygen enhances the antiviral innate response via EGLN1 hydroxylation of IRF3.
- Xing Liu
- , Jinhua Tang
- & Wuhan Xiao
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