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A plant RNA virus inhibits NPR1 sumoylation and subverts NPR1-mediated plant immunity
Salicylic acid (SA) signaling pathway restricts the compatible infection of potyviruses. Here, Liu et al. show that potyviral NIb interacts with NPR1, the SA receptor in plants, preventing its sumoylation by SUMO3 and subsequent phosphorylation at Ser11/Ser15. This way, NPR1-mediated immunity is suppressed to promote virus infection.
- Jiahui Liu
- , Xiaoyun Wu
- & Xiaofei Cheng
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Article
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Engineering potent live attenuated coronavirus vaccines by targeted inactivation of the immune evasive viral deubiquitinase
In this work, authors provide a proof-of-concept study showing that deubiquitinating enzyme inactivation in MERS-CoV leads to attenuation in mice, and protection against a lethal challenge.
- Sebenzile K. Myeni
- , Peter J. Bredenbeek
- & Marjolein Kikkert
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Article
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BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants
SARS-CoV-2 omicron variant BA.1 has shown increased transmissibility and immune escape, relative to previous SARS-CoV-2 variants. In this study, authors utilise antigenic cartography to characterise the neutralisation profiles of omicron sub-lineages, BA.2 and BA.5, in comparison to BA.1 and pre-omicron variants.
- Annika Rössler
- , Antonia Netzl
- & Janine Kimpel
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Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes
Human coronavirus OC43 causes respiratory disease and is maintained in the human population through recurring infections. Here, by extensive structural analyses, the authors provide insights into the binding sites and breadth of neutralizing antibodies against this endemic coronavirus.
- Chunyan Wang
- , Emma L. Hesketh
- & Berend-Jan Bosch
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Article
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HPV infection alters vaginal microbiome through down-regulating host mucosal innate peptides used by Lactobacilli as amino acid sources
Here, the authors show that HPV infection leads to downregulation of host mucosal innate peptides, which are in turn used by predominant Lactobacillus species as amino acid source, promoting ultimately an imbalance in the vaginal flora.
- Alizee Lebeau
- , Diane Bruyere
- & Michael Herfs
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Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5
MERS-CoV is enzootic in dromedary camels, can spread to humans but undergoes limited onward transmission. Here, Schroeder et al. compare clinical isolates of MERS-CoV in vitro and show that the predominantly circulating recombinant lineage 5 possess a fitness advantage over parental lineage 3 and 4 due to reduced activation of innate immune signaling.
- Simon Schroeder
- , Christin Mache
- & Christian Drosten
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Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants
Here, the authors characterize the neutralization capacity of post-Sputnik V vaccination sera against SARS-CoV-2 variants of concern B.1.1.7 (alpha) and B.1.351 (beta), showing the latter to exhibit resistance to neutralization in vitro.
- Satoshi Ikegame
- , Mohammed N. A. Siddiquey
- & Benhur Lee
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An epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways
The CD8 T cell response to Zika virus is known to be a critical component of the host immune response to infection. Here the authors show a Zika virus isolate specific disruption of antigen processing that impacts the host response and impairs viral clearance providing evidence of isolate specific impacts on the immune response to infection
- Ryan D. Pardy
- , Stefanie F. Valbon
- & Martin J. Richer
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Vulnerabilities in coronavirus glycan shields despite extensive glycosylation
Glycosylation plays a key role in shielding of immunogenic epitopes on viral spike (S) proteins. Here Watanabe et al. report that glycans of coronavirus SARS and MERS S proteins are heterogeneously distributed and do not form an efficacious high-density global shield which would ensure efficient immune evasion.
- Yasunori Watanabe
- , Zachary T. Berndsen
- & Max Crispin
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Immune-profiling of ZIKV-infected patients identifies a distinct function of plasmacytoid dendritic cells for immune cross-regulation
Zika virus (ZIKV) poses a significant public health threat, but the immune landscape changes following ZIKV infection is still unclear. Here, the authors show, using flow cytometry and transcriptomic data, that ZIKV induces a multitude of immune responses, with plasmacytoid dendritic cells poised centrally to interact with other immune cell types.
- Xiaoming Sun
- , Stephane Hua
- & Xu G. Yu
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Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape
Antigenic site B in influenza A virus hemagglutinin (HA) is immunodominant in circulating human H3N2 strains. Using deep mutational scanning, Wu et al. here define the local fitness landscapes of HA antigenic site B in six human H3N2 strains, providing insights into evolvability of influenza antigenicity.
- Nicholas C. Wu
- , Jakub Otwinowski
- & Ian A. Wilson
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Regulation of the linear ubiquitination of STAT1 controls antiviral interferon signaling
LUBAC is involved in adding linear ubiquitin chains to important immune signaling proteins. Here the authors show that this mechanism is effective in inhibiting STAT1-mediated interferon signaling, and that the deubiquitinase OTULIN can remove these linear ubiquitins from STAT1 to reactivate this antiviral signaling pathway.
- Yibo Zuo
- , Qian Feng
- & Hui Zheng
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HCMV-encoded US7 and US8 act as antagonists of innate immunity by distinctively targeting TLR-signaling pathways
Human cytomegalovirus (HCMV) has evolved several mechanisms to evade the host immune response. Here, Park et al. show that HCMV-encoded US7 and US8 proteins bind TLR3 and TLR4 and facilitate TLR degradation by distinct mechanisms, including ER-associated and lysosomal degradation.
- Areum Park
- , Eun A. Ra
- & Boyoun Park
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Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor
Human cytomegalovirus (HCMV) can persist for the life of a host in the face of robust immune responses owing to a wide range of immune evasion strategies. Here Liu and colleagues show that HCMV evades the IgG-mediated response by the endoplasmic reticulum-associated degradation of the neonatal Fc receptor for IgG.
- Xiaoyang Liu
- , Senthilkumar Palaniyandi
- & Xiaoping Zhu
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Differential human antibody repertoires following Zika infection and the implications for serodiagnostics and disease outcome
In the current study, the authors profile the IgG and IgM antibody repertoires that develop over 7 days following acute Zika virus infection. Using urine and serum samples from infected human patients the authors identify new biomarkers for serodiagnosis of Zika virus.
- Supriya Ravichandran
- , Megan Hahn
- & Surender Khurana
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PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation
The accessory lentiviral protein X (Vpx) of the SIVsmm/mac and HIV-2 lineage targets the host-restriction factor SAMHD1 for proteasomal degradation. Here, the authors show that host PIM kinase-mediated phosphorylation of Vpx stabilizes its interaction with SAMHD1, suggesting PIM as potential antiviral targets.
- Kei Miyakawa
- , Satoko Matsunaga
- & Akihide Ryo
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Article
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A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding
Secreted cytokine decoy receptors encoded by viruses can act as potent immune evasion proteins modulating antiviral immunity. Here Hernaez et al. show that cell surface binding is required for efficient evasion of the host response by a secreted virus encoded type I IFN decoy receptor of vaccinia and ectromelia virus using an in vivo model of infection.
- Bruno Hernáez
- , Juan Manuel Alonso-Lobo
- & Antonio Alcamí
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A naturally protective epitope of limited variability as an influenza vaccine target
Current influenza vaccine approaches largely focus on highly variable epitopes with high immunogenicity or epitopes of low variability that often have low immunogenicity. Here, Thompson et al. identify a highly immunogenic epitope of limited variability in the head domain of the H1 haemagglutinin and show protection from diverse H1N1 strains in mice.
- Craig P. Thompson
- , José Lourenço
- & Sunetra Gupta
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An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction
The Asian lineage of Zika virus (ZIKV) has acquired a mutation in NS1 that enhances mosquito infection. Here, Xia et al. show that the same mutation interferes with interferon production through interaction with TBK1 and affects ZIKV replication in mice.
- Hongjie Xia
- , Huanle Luo
- & Pei-Yong Shi
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Human cytomegalovirus-encoded US9 targets MAVS and STING signaling to evade type I interferon immune responses
MAVS and STING signaling are central to interferon-inducing antiviral immunity. Here, the authors show how the human cytomegalovirus protein US9 can evade this immunity by antagonizing these pathways.
- Hyun jin Choi
- , Areum Park
- & Boyoun Park
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Article
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Hepatitis B virus persistence in mice reveals IL-21 and IL-33 as regulators of viral clearance
Hepatitis B virus (HBV) establishes chronic infection in only some patients, but the mechanisms underlying clearance failure in these patients are not fully understood. Here, the authors identify and characterize an HBV strain that can persist in mice and show that IL-21 and IL-33 responses contribute to clearance.
- Zhongliang Shen
- , Huijuan Yang
- & Jing Liu
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Article
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Pandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic cell death
The differences in virus-host interactions resulting in distinct pathogenicity of seasonal and pandemic influenza A viruses (IAV) are not well understood. Here, the authors show that the hemagglutinin segment from pandemic, but not seasonal, IAV suppresses RIPK3-mediated dendritic cell death, thereby reducing T cell activation.
- Boris M. Hartmann
- , Randy A. Albrecht
- & Stuart C. Sealfon
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Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein
Monoclonal antibodies to prevent respiratory syncytial virus (RSV) disease are under development, but the molecular requirements for cross-subtype neutralization are unclear. Here, the authors show that residue 201 in RSV fusion protein determines subtype specific neutralization for the clinically-relevant monoclonal antibody, 5C4.
- Daiyin Tian
- , Michael B. Battles
- & Barney S. Graham
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Receptor-binding loops in alphacoronavirus adaptation and evolution
Coronaviruses have a relatively high mutation rate, potentially allowing fast adaptation to changing pressures. Here, Wong et al. provide the structure of the receptor-binding domain (RBD) of the human coronavirus HCoV-229E and its receptor and analyze the evolution of the RBD over the past 50 years.
- Alan H. M. Wong
- , Aidan C. A. Tomlinson
- & James M. Rini
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TRIM29 promotes DNA virus infections by inhibiting innate immune response
Proteins of the TRIM family have regulatory functions in immune signaling, often via ubiquitination of target proteins. Here, the authors show that TRIM29 is induced upon infection with DNA viruses, resulting in degradation of STING, decreased interferon signaling and increased pathogenicity in mice.
- Junji Xing
- , Ao Zhang
- & Zhiqiang Zhang
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Article
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The interferon-related developmental regulator 1 is used by human papillomavirus to suppress NFκB activation
Human papillomavirus employs immune evasion strategies to establish a long-term infection. Here the authors show that the virus in the EGFR-dependent manner induces IFRD1, which blocks NFκB activating acetylation, and that this process can be suppressed by the EGFR inhibitor cetuximab.
- Bart Tummers
- , Renske Goedemans
- & Sjoerd H. van der Burg
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Interleukin-1α released from HSV-1-infected keratinocytes acts as a functional alarmin in the skin
HSV-1 is known to evade the immune system by retention of interleukin-1β. Here, the authors show that HSV-1-infected keratinocytes circumvent this mechanism by release of interleukin-1α, which recruits leukocytes and prevents viral dissemination.
- Katelynn A. Milora
- , Samantha L. Miller
- & Liselotte E. Jensen
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HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection
Herpes simplex virus type 1 infects human skin and mucous membranes. MacLeod and colleagues identify MARCO as a novel cell-surface receptor bound by herpes simplex virus type 1, and show that this interaction enhances infection of keratinocytes and promotes the development of skin lesions in mice.
- Daniel T. MacLeod
- , Teruaki Nakatsuji
- & Richard L. Gallo
Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3