Evolutionary selection on MDA5 and LGP2 in the chicken preserves antiviral competence in the absence of RIG-I

<正>The pattern recognition receptors (PRRs) act as the first line of defense against pathogens and are common molecular targets in the conflict between viruses and their host (Tan et al.,2018).The RIG-I-like receptors (RLRs),including RIG-I (Yoneyama et al.,2004),MDA5 (Andrejeva et al.,2004),and LGP2 (Saito et al.,2007),are PRRs and reside in the cytoplasm.These proteins recognize the RNA structures of different viral RNA species.All RLRs have an intermediate RNA helicase domain that catalyzes ATP hydrolysis and a C-terminal domain (CTD).RIG-I and MDA5,but not LGP2,contain tandem caspase recruitment domains at their N-termini     

Interaction between Bms1 and Rcl1,two ribosome biogenesis factors,is evolutionally conserved in zebrafish and human

正Ribosomes are large RNA and protein complexes that function as the machinery for translation protein synthesis(Boisvert et al.,2007;Ben-Shem et al.,2011;Henras et al.,2015;Khatter et al.,2015;McCann et al.,2015).The eukaryotic ribosome is composed of two subunits,the 60S large subunit(LSU)and the 40S small subunit(SSU),which collectively comprise of four different ribosomal RNA(rRNA)species and more than 70 proteins(Ben-Shem et al.,2011;Henras et al.,2015;Khatter et al.,2015).The LSU contains     

Development of a SYBR-based real-time PCR to detect rabbit hemorrhagic disease virus (RHDV) and analyze its tissue distribution in experimentally infected rabbits

<正>Dear Editor,Rabbit hemorrhagic disease(RHD)is a highly contagious disease of both wild and domesticated rabbits(Oryctolagus cuniculus).The causative agent of the disease is the rabbit hemorrhagic disease virus(RHDV),belongs to the genus Lagovirus within the family Caliciviridae(Granzow et al.,1996;Ohlinger et al.,1990).It is a small and non-enveloped virus with a 7.5 kb single stranded positive sense RNA genome(Meyers et al.,1991;Meyers et al.,2000).Based on an analysis of VP60     

Structure-activity relationship optimization for lassa virus fusion inhibitors targeting the transmembrane domain of GP2

Dear Editor,Lassa virus(LASV)belongs to the Mammarenavirus genus,Arenaviridae family.Arenaviruses are classified into two main groups-Old World(OW)and New World(NW)-based on virus genetics,serology,antigenic properties and geographical relationships.The OW LASV and Lujo virus(LUJV),as well as NW Jurn'n virus(JUNV),Machupo virus(MACV),Guanarito virus(GTOV),Sabia virus(SABV)and Chapare virus(CHAPV),are known to cause severe hemorrhagic fever and are listed as biosafety level 4(BSL-4)agents.The arenavirus glycoprotein complex(GPC)contains three subunits-the retained stable-signal peptide(SSP),the receptor-binding subunit GP1,and the membrane fusion subunit GP2(Lenz et al.,2001).Notably,the proximate external membrane region and TM of GP2,together with the ectodomain loop and TMs of SSP,form an SSP-GP2 interface,playing essential roles in regulating membrane fusion,and providing targets for distinct fusion inhibitors(Larson et al.,2008;Lee et al.,2008;York et al.,2008;York and Nunberg,2009;Thomas et al.,2011;Burgeson et al.,2013a;Shankar et al.,2016;Wang et al.,2016;Wang et al.,2018).Among these inhibitors,ST-161 is LASV specific(Burgeson et al.,2013a).In this study,we conducted structure-activity relationship(SAR)optimization of ST-161.As a result,21 derivatives with IC50 values<1 pmol/L are presented in Table S1.Hit compounds 21,29 and 57 exhibiting robust inhibition of the LASV pseudotype virus(LASVpv,VSV backbone enveloped by LASV GPC with single cycle infection)entry with IC50 values lower than 0.2 nmol/L(Figs.1A and S1),as well as hit compound 72 with an ester bond instead of acylhydrazone,were further investigated.To test whether the four hit compounds inhibit LASV entry by blocking the GPC-mediated membrane fusion,the inhibition effects of these compounds against LASV GPC mediated fusion were quantitatively determined by dual-luciferase assay(Thomas et al.,2011;Wang et al.,2018).     

Heterologous viral suppressor of RNA silencing breaks protein-based viral immunity in mixed viral infection

正Dear Editor:RNA silencing confers immunity against most viruses and is initiated by host Dicer processing of viral doublestranded RNA into virus-derived small interfering RNA(si RNA)(Guo et al., 2019). Viruses that cause plant disease usually evolve viral suppressor of RNA silencing(VSR) to inhibit antiviral silencing (Li and Ding, 2006).Some plant nucleotide-binding leucine-rich repeat proteins (NLRs) emerge as immune receptors to recognize specific virus and trigger rapid hypersensitive response(HR) at infection site to protect plants from devastating viruses (Cui et al., 2015; Deng et al., 2018).     

RNA methylation regulates hematopoietic stem/progenitor cell specification

正RNA methylation,conceptually similar to methylation of DNA and protein,has been identified in m RNAs and noncoding RNAs(nc RNAs)(Niu et al.,2013).In particular,N6-methyl-adenosine(m~6A)is the most prevalent m RNA modification in eukaryotes(Jia et al.,2013).New insights into the biological functions of m~6A modification have been recently gained due to the rapid development of highthroughput sequencing technologies.m RNAs are methylated     

Human rhinovirus C infection is associated with asthma in children determined by xTAG respiratory viral panel FAST

<正>Dear Editor,Cumulative evidence supports the role of early-life viral infections,especially respiratory syncytial virus(RSV)and human rhinovirus(HRV),as major antecedents of childhood asthma(Lemanske,2002;Jackson et al.,2008).In this study,the x TAG respiratory viral panel FAST(RVP FAST)assay,a multiplex polymerase chain reaction(PCR)-based method(Arens et al.,2010;BaladaLlasat et al.,2011;Gharabaghi et al.,2011;Selvaraju,2012),was used to investigate the association of infec-     

Noncoding RNA: from dark matter to bright star

正The central dogma states that genes encoded in the DNA should be first transcribed into messenger RNA (mRNA) and then translated into functional proteins (Crick, 1970). This dogma has been written in numerous textbooks and learned by myriad students. However, along with the completion of the human genome project in June 2000, an astonishing fact was revealed:only 1.5%of the human genome encodes for proteins (Lander et al., 2001; Venter et al., 2001). This fact     

An Assessment of Amplicon-Sequencing Based Method for Viral Intrahost Analysis

正Dear Editor,RNA virus features the high per-generation mutation rate,resulting in highly diversified population, which determines viral phenotypes and fitness (Domingo et al. 2012).The development of deep sequencing and bioinformatic techniques paves the way to study viral population genetics at an intrahost level, and has provided new insights into     

Engrafted newborn neurons could functionally integrate into the host neuronal network

The limited capability to regenerate new neurons following injuries of the central neural system (CNS) still remains a major challenge for basic and clinical neuroscience.Neural stem cells (NSCs) could nearly have the potential to differentiate into all kinds of neural cells in vitro.Previous studies verified that exogenous transplanted NSCs are capable of differentiating into neurons and projecting onto the host neurons in the rat brain (Tabar et al.,2005;Dong JR et al.,2012),which could lead to behavioral recovery from neuronal damages such as spinal cord injury (McDonald et al.,1999),Parkinson's disease (Gonzalez et al.,2015;Kim et al.,2002;Lindvall,2001),and stroke (Zhang et al.,2016).     

Analysis of non-coding small RNA similarity/sharing between plant and animal genomes

<正>Dear Editor,During the construction and analysis of the Bencao(herbal)small RNA(s RNA) Atlas, the fact that many s RNAs from the human genome are present in the Bencao(herbal) database attracted our attention(Cao et al., 2023). The Bencao Atlas contains millions of s RNAs from hundreds of plants used in traditional Chinese Medicines(TCMs). Therefore,     

A new record of the capped langur (Trachypithecus pileatus) in China

DEAR EDITOR, The distribution of the capped langur (Trachypithecus pileatus)in China has become controversial since Shortridge's langur (Trachypithecus shortridgei) was upgraded to a full species.The capped langur is considered to be distributed in northeast India,Bangladesh,Bhutan,and northwest Myanmar only (Brandon-Jones et al.,2004;Choudhury,2008,2014;Das et al.,2008;Groves,2001).In our field survey,however,we obtained photos of the capped langur,demonstrating its existence in China. Following the species promotion of Shortridge's langur (Brandon-Jones et al.,2004;Groves,2001) and the delimiting of its distribution range to northwestern Yunnan in China and northeastern Myanmar (Brandon-Jones et al.,2004;Cui et al.,2016;Das et al.,2008;Groves,2001;Htun et al.,2008),with a new record in southeastern Tibet (Wu et al.,2016),the capped langur has been deleted from the checklist of mammals in China (Jiang et al.,2015).Despite this,Dr.George Schaller has suggested that capped langurs might exist in the northeastern section of the Yarlung-Zangbo River (Choudhury,2008).     

N-terminal domain of the RNA polymerase of very virulent infectious bursal disease virus contributes to viral replication and virulence

正Dear Editor,Infectious bursal disease virus (IBDV) causes an economically significant disease of chickens worldwide (Berg,2000). The molecular basis for the virulence of very virulent IBDV (vvIBDV) is not fully understood. Previous studies have shown that genome segment A, especically VP2 protein, plays the most important role in the tropism and pathogenicity of serotype 1 IBDV (Brandt et al., 2001). VP2 is,however, unlikely to be the only factor for the virulence of vvIBDV (Boot et al., 2000). A chrono-phylogenetic study suggested that the worldwide expansion of vvIBDV likely     

Molecular mechanisms of coronavirus RNA capping and methylation

The 5′-cap structures of eukaryotic m RNAs are important for RNA stability, pre-m RNA splicing,m RNA export, and protein translation. Many viruses have evolved mechanisms for generating their own cap structures with methylation at the N7 position of the capped guanine and the ribose 2′-Oposition of the first nucleotide, which help viral RNAs escape recognition by the host innate immune system. The RNA genomes of coronavirus were identified to have 5′-caps in the early1980 s. However, for decades the RNA capping mechanisms of coronaviruses remained unknown.Since 2003, the outbreak of severe acute respiratory syndrome coronavirus has drawn increased attention and stimulated numerous studies on the molecular virology of coronaviruses. Here, we review the current understanding of the mechanisms adopted by coronaviruses to produce the 5′-cap structure and methylation modification of viral genomic RNAs.     

OsRFPH2-10, a RING-H2 Finger E3 Ubiquitin Ligase,Is Involved in Rice Antiviral Defense in the Early Stages of Rice dwarf virus Infection

Dear Editor, Rice dwarf virus （RDV）, a member of the Phytoreoviurs genus, is transmitted to rice （Oryza sativa） plants by leaf- hopper （Nephotettix cincticeps） in a propagative manner. Infection by RDV results in severe stunting growth pheno- types and a dramatic reduction in grain yield. The genome of RDV is composed of 12-segmented double-stranded RNAs （S1-S12 based on their migration rates in agarose gel electro- phoresis）. The 12 segments encode seven structural proteins （P1, P2, P3, P5, P7, P8, and P9 as the products of Sl, S2, S3, S5, S7, S8, and S9, respectively） and five nonstructural proteins （Pns4, Pns6, Pnsl0, Pns11, and Pns12 as the products of S4, S6, S10, S11, and S12, respectively）. The outer capsid protein P2 is essential for RDV infection of insects and thus influences transmission of RDV by the insect vector （Omura et al., 1998; Zhou et al., 2007）. P2 also contributes to the dwarf phenotype of infected rice by interfering with gibberellic acid synthesis （Zhu et al., 2005）. When RDV-infected rice plants were main- tained via vegetative propagation for several years without insect transmission, they regained normal growth height due to loss of RDV P2 and Pnsl0 proteins （Pu et al., 2011）.