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Cryo-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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The 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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Deciphering 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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Structural 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
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The 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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The 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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MYADM binds human parechovirus 1 and is essential for viral entry
Host factors required for parechovirus entry are not well understood. Here, the authors identify MYADM as an essential host entry factor that directly binds human parechovirus 1 and that is required for PeV-A infection in cell lines and human gastrointestinal epithelial organoids.
- Wenjie Qiao
- , Christopher M. Richards
- & Jan E. Carette
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Neuronal miR-9 promotes HSV-1 epigenetic silencing and latency by repressing Oct-1 and Onecut family genes
Here, the authors identify neuron-specific miR-9 that potentially blocks HSV-1 neuronal replication by targeting host OCT-1 and ONECUT transcription factors involved in epigenetic activation of HSV-1 productive-cycle genes. Thus miR-9 promotes viral epigenetic silencing and latent infection in neurons.
- Yue Deng
- , Yuqi Lin
- & Dongli Pan
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Transmission and dynamics of mother-infant gut viruses during pregnancy and early life
Gut ecosystem colonization impacts lifelong health. Here, authors track mother-infant gut viruses over time, reveal feeding’s influence on early viral colonization, and demonstrate the co-transmission of bacteriophages and bacteria from mothers to infants.
- Sanzhima Garmaeva
- , Trishla Sinha
- & Alexandra Zhernakova
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Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells
Human cytomegalovirus (HCMV) is a ubiquitous pathogen associated with morbidity and mortality in the immunocompromised or immunonaive context. Here the authors show that HCMV exploits STING signalling and subverts the interferon response to support infection of monocyte derive dendritic cells.
- Bibiana Costa
- , Jennifer Becker
- & Ulrich Kalinke
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Nucleocapsid protein-specific monoclonal antibodies protect mice against Crimean-Congo hemorrhagic fever virus
There are limited treatment options for infection with Crimean-Congo hemorrhagic fever virus in humans. Here, the authors show that a monoclonal antibody targeting the highly conserved viral nucleocapsid protein provides protective effects in a mouse model of infection.
- Aura R. Garrison
- , Vanessa Moresco
- & Joseph W. Golden
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Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus
The oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) is known to reprogram cellular metabolism. Here, Wan et al show that viral Cyclin exploits host nucleotide synthesis and glycolysis to support KSHV pathogenesis.
- Quanyuan Wan
- , Leah Tavakoli
- & Jun Zhao
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Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant
XBB.1.5 of SARS-CoV-2 is a descendant of XBB.1 and has mutations in spike and ORF8, making it more infectious to humans. Here, the authors examined in detail the differences in virological properties of the two variants.
- Tomokazu Tamura
- , Takashi Irie
- & Takasuke Fukuhara
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The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
The cellular RNA polymerase II C-terminal domain is known to support transcription of influenza virus mRNAs. Here, Krischuns et al. use cell-based and in vitro approaches to demonstrate that it also plays a role in replication of the viral genome.
- Tim Krischuns
- , Benoît Arragain
- & Nadia Naffakh
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Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats
The ecology of Ebola virus (EBOV) is still largely unclear. Here, the authors show that Angolan freetailed bats are selectively permissive to EBOV infection, but not to other filoviruses, and demonstrate EBOV placental tissue tropism indicating potential horizontal and vertical transmission between conspecifics.
- S. A. Riesle-Sbarbaro
- , G. Wibbelt
- & A. Kurth
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EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses
Alpha-(1,6)-fucosyltransferase (FUT8) is the sole enzyme responsible for core fucosylation of N-glycans during glycoprotein biosynthesis. Here the authors show that HCV envelope protein E2 enhances FUT8 expression through the EGFR-AKT-SNAIL axis, which subsequently promotes RIG-I K48-ubiquitination and dampens the antiviral IFN-I response through core fucosylated-EGFR-JAK1-STAT3-RIG-I pathway.
- Qiu Pan
- , Yan Xie
- & Xiao-Lian Zhang
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LDLR is used as a cell entry receptor by multiple alphaviruses
Getah virus (GETV), is a mosquito-borne alphavirus of importance in veterinary medicine. Here, the authors show that evolutionarily conserved low-density lipoprotein receptor (LDLR) functions as a receptor for GETV, which may explain the multi-species spread of this virus.
- Xiaofeng Zhai
- , Xiaoling Li
- & Shuo Su
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Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex
Epstein-Barr virus causes lymphoma. Here the authors describe a direct complex of the viral oncoprotein LMP1 with the cellular TRAF6 protein as a critical virus-host interface for lymphoma survival and validate this complex as a potential therapeutic target.
- Fabian Giehler
- , Michael S. Ostertag
- & Arnd Kieser
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Nuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1
Here, Huang et al. show that nuclear membrane proteins SUN2 and Nesprins are required for the in vitro and in vivo replication of Zika virus, through directing the cytoskeleton remodeling and formation of replication organelles mediated by viral NS1.
- Yanxia Huang
- , Qinyu Peng
- & Ping Zhang
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Direct translation of incoming retroviral genomes
A defining feature of retroviruses compared to other +ssRNA viruses is reverse transcription. Here, Köppke et al. show that retroviruses (e.g. HIV-1) can produce viral proteins even in the absence of reverse transcription.
- Julia Köppke
- , Luise-Elektra Keller
- & Oya Cingöz
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Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication
Bacteriophages have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. Here, Maffei et al. show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates; however, a particular phage can directly replicate and induce the lysis of deep-dormant hosts.
- Enea Maffei
- , Anne-Kathrin Woischnig
- & Alexander Harms
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Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1
How SARS-CoV-2 enters cells and causes COVID-19 is still under intensive investigation. Here, the authors identify unexpected crosstalk between human coronavirus and filovirus entry and discover pan-inhibitors for these highly pathogenic viruses.
- Ilyas Khan
- , Sunan Li
- & Yong-Hui Zheng
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NDP52 mediates an antiviral response to hepatitis B virus infection through Rab9-dependent lysosomal degradation pathway
The nuclear dot protein 52 (NDP52) is an autophagy receptor known to trigger autophagy following bacterial infection. Here, Cui et al. show that NDP52 also triggers an anti-viral response following hepatitis B virus (HBV) infection. NDP52 forms a tripartite complex with Rab9 and envelope proteins of HBV and targets the virus to Rab9-dependent lysosomal degradation pathway.
- Shuzhi Cui
- , Tian Xia
- & Yu Wei
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The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection
NEIL2, a mammalian DNA repair enzyme, has been reported to suppress infection induced inflammation. Here, the authors characterize its role in modulating the severity of SARS-CoV-2 infection.
- Nisha Tapryal
- , Anirban Chakraborty
- & Tapas K. Hazra
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Article
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Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways
This study reveals the recruitment of several cellular enzymes involved in redox and methylation processes, to endoplasmic reticulum membranes remodeled by Zika virus. These proteins regulate stability, folding and modifications of viral proteins or RNA.
- Solène Denolly
- , Alexey Stukalov
- & Ralf Bartenschlager
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The poxvirus F17 protein counteracts mitochondrially orchestrated antiviral responses
Poxviruses replicate in the cytoplasm, making them vulnerable to detection by host nucleic acid sensors. Here the authors show that poxvirus replication induces mitochondrial hyperfusion, resulting in the release of mitochondrial DNA, but that the poxvirus F17 protein counteracts ensuing cGAS activation and increase in glycolysis.
- Nathan Meade
- , Helen K. Toreev
- & Derek Walsh
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Interrogating ligand-receptor interactions using highly sensitive cellular biosensors
The interaction of membrane-resident proteins plays an essential role in biological processes. Here the authors describe cellular biosensors based on chimeric receptors, as a tool to study the interaction of receptor-ligand pairs such as immune checkpoint molecules or virus attachment proteins and their receptors.
- Maximilian A. Funk
- , Judith Leitner
- & Peter Steinberger
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H3.1K27me1 loss confers Arabidopsis resistance to Geminivirus by sequestering DNA repair proteins onto host genome
Geminiviruses hijack the host DNA repairing proteins for their amplification. The authors report that Arabidopsis loses H3.1K27me1, a protector of genome stability, but gains resistance to geminivirus infection via retaining key factors like RAD51.
- Zhen Wang
- , Claudia M. Castillo-González
- & Xiuren Zhang
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Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins
Here, Ning et al report the cellular interactomes of Crimean-Congo haemorrhagic fever virus glycoproteins and uncover a host restriction factor HAX1 that hijacks the viral glycoproteins to mitochondria, disabling progeny virion packaging.
- Shiyu Dai
- , Yuan-Qin Min
- & Yun-Jia Ning
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Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly
This study reveals the association of cholesterol with the Zika virus prM protein. It highlights the role of cholesterol during virus entry and assembly and shows the incorporation of cholesterol into the viral envelope.
- Sarah Goellner
- , Giray Enkavi
- & Ralf Bartenschlager
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Co-option of a non-retroviral endogenous viral element in planthoppers
Non-retroviral endogenous viral elements are widely dispersed in eukaryotic genomes, but their functions remain largely unknown. Here, Huang et al show that one such element in planthoppers has been co-opted and contributes to insect fitness..
- Hai-Jian Huang
- , Yi-Yuan Li
- & Jun-Min Li
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Defining neutralization and allostery by antibodies against COVID-19 variants
Here, Tulsian et al. identified the effect of biologically relevant full-length IgG binding on the Spike protein from different SARS-CoV-2 variants to comprehensively understand the mechanisms of antibody evasion, towards the development of better antiviral strategies.
- Nikhil Kumar Tulsian
- , Raghuvamsi Venkata Palur
- & Paul Anthony MacAry
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Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection
Bats are natural reservoirs for several zoonotic viruses including SARS-CoV-2 thus there is a need to better define bat antiviral responses. Here, Hashimi et al. profile antiviral responses to SARS-CoV-2 in bat intestinal organoids finding that interferon and regenerative responses where induced.
- Marziah Hashimi
- , T. Andrew Sebrell
- & Diane Bimczok
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FHL1 promotes chikungunya and o’nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design
FHL1A is a crucial host factor for alphavirus infection but its impact on pathogenesis is unclear. Here, the authors use a FHL1−/− knockout mouse model to show that the FHL1 splice variant impacts arthritis and myositis after chikungunya or o’nyong-nyong infections but not Ross River or mayaro virus infection.
- Wern Hann Ng
- , Xiang Liu
- & Suresh Mahalingam
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Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections
Host factors involved in filovirus infection are incompletely understood. Here, the authors used a haploid cell screening system to unveil CCZ1’s crucial role in regulating endosomal trafficking thus virus movement within cells and thereby impacting Marburg and Ebola infection.
- Vanessa Monteil
- , Hyesoo Kwon
- & Ali Mirazimi
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An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization
Despite their essentiality, human ANP32A and ANP32B are redundant host factors for influenza virus genome replication. In this work, authors show that an influenza virus grown in cells lacking ANP32A and ANP32B evolved to use ANP32E. They explore the polymerase mutations that enable this, and demonstrate increased virulence in mice.
- Carol M. Sheppard
- , Daniel H. Goldhill
- & Wendy S. Barclay
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A human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes
Cross-neutralizing activity of monoclonal antibodies against poliovirus serotypes is less commonly reported. In this study, the authors use high-resolution cryo-EM to reveal that a cross-neutralizing human antibody neutralizes all three poliovirus serotypes by interacting with the receptor-binding region, called the canyon.
- Andrew J. Charnesky
- , Julia E. Faust
- & Susan L. Hafenstein
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NAT10-dependent N4‐acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation
N-acetyltransferase 10 (NAT10) is an N4‐acetylcytidine (ac4C) writer, which catalyzes RNA acetylation at cytidine N4 position on RNAs. Here, the authors show that NAT10 catalyzes ac4C addition to a long non-coding RNA encoded by the oncogenic DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency, which promotes NAT10 recruitment of IFI16 mRNA, resulting in inflammasome activation.
- Qin Yan
- , Jing Zhou
- & Chun Lu
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Article
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Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq
Sunshine et al. use Perturb-seq to study host dependencies of SARS-CoV-2 by inactivating host factors genetically and monitoring the course of infection by single-cell sequencing, characterizing global host phenotypes. They identified NFKBIA, EIF4E2 and EIF4H as strong host dependency factors.
- Sara Sunshine
- , Andreas S. Puschnik
- & Marco Y. Hein
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Article
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Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets
Using a multi-OMICS approach, Haas et al identify 54 human genes and 16 host-targeting chemical compounds that regulate influenza A virus infection in lung epithelial cells, including AHNAK and COBP1 which are also essential for SARS-CoV-2 infection.
- Kelsey M. Haas
- , Michael J. McGregor
- & Nevan J. Krogan
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| Open Access
A systematic analysis of marine lysogens and proviruses
Viruses are ubiquitous in the oceans, exhibiting high abundance and diversity. Here, Yi et al. present a systematic catalogue and analysis of genomic sequences from marine prokaryotes and their proviruses, thus contributing to a better understanding of the ecology of these microorganisms.
- Yi Yi
- , Shunzhang Liu
- & Huahua Jian
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Article
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Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2
Here, the authors analysed immune response to two consecutive coronavirus infections and observed that hamsters infected with seasonal coronaviruses were not protected from COVID-19 despite cross-reactive antibodies. Antiviral and germinal center B cell responses were suppressed but not during SARS-CoV-2 variant infections.
- Magen E. Francis
- , Ethan B. Jansen
- & Alyson A. Kelvin
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A subset of viruses thrives following microbial resuscitation during rewetting of a seasonally dry California grassland soil
Rewetting of seasonally dry soils induces dramatic shifts in viral biomass and diversity. Combining stable isotope probing, metagenomics, and viromics Nicolas et al. provide evidence that viral lysis contributes to microbial turnover and the associated CO2 efflux.
- Alexa M. Nicolas
- , Ella T. Sieradzki
- & Steven J. Blazewicz
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| Open Access
A plant cytorhabdovirus modulates locomotor activity of insect vectors to enhance virus transmission
Most plant viruses are transmitted by insect vectors in finely regulatory mechanisms. Here, the authors show that a plant rhabdovirus can modify circadian rhythm of its insect vectors and enhances locomotor activity for efficient transmission.
- Dong-Min Gao
- , Ji-Hui Qiao
- & Xian-Bing Wang
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Article
| Open Access
Facile hermetic TEM grid preparation for molecular imaging of hydrated biological samples at room temperature
Electron microscopy of native hydrated biological samples close to physiological temperature is challenging. Here, authors encapsulate proteins and cells as an efficient, cost-effective complement to other microscopy technique in addressing biological questions at the molecular level.
- Lingli Kong
- , Jianfang Liu
- & Gang Ren
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Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids
The pathological effects of Zika virus (ZIKV) infection on placental trophoblast progenitor cells in early human embryos are not well understood. In this study, using human trophoblast stem cells (hTSCs), Wu et al. show that hTSCs are readily infected by ZIKV, but that there is increasing resistance to the virus as differentiation towards mature lineages proceeds.
- Hao Wu
- , Xing-Yao Huang
- & Cheng-Feng Qin
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Dynamically regulated two-site interaction of viral RNA to capture host translation initiation factor
RNA viruses use elements of their genomic RNA to commandeer the host translational machinery. Here, the authors use NMR and cryo-EM to reveal the sophisticated strategy by which a viral RNA engages host translational factors in a dynamically regulated two-site interaction.
- Shunsuke Imai
- , Hiroshi Suzuki
- & Ichio Shimada
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Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H
HIV-1 Vif antagonizes multiple human APOBEC3 cytidine deaminases for immune evasion. Here, the authors determine the structure of human APOBEC3H bound to HIV-1 Vif and E3 ubiquitin ligase, providing a mechanistic basis for the virus-host arms race.
- Fumiaki Ito
- , Ana L. Alvarez-Cabrera
- & Xiaojiang S. Chen
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Structural and functional insights into the modulation of T cell costimulation by monkeypox virus protein M2
The B7 family proteins B7.1 (CD80) and B7.2 (CD86) are two well-studied costimulatory ligands that play critical roles in host T cell immunity against viral infection. In this study, the authors show that oligomeric M2 protein encoded by monkeypox virus serves as a viral decoy receptor and inhibits T cell activation mediated by hB7.1/2 co-stimulation via the blockade of CD28 binding to human B7.1/2, providing molecular mechanisms of poxvirus M2 function and immune evasion.
- Shangyu Yang
- , Yong Wang
- & Haiyan Zhao
Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication