Abstract:
:Noroviruses (NoVs) are a leading cause of gastroenteritis worldwide, yet host factors that restrict NoV replication are not well understood. Here, we use a CRISPR activation genome-wide screening to identify host genes that can inhibit murine norovirus (MNoV) replication in human cells. Our screens identified with high confidence 49 genes that can inhibit MNoV infection when overexpressed. A significant number of these genes are in interferon and immune regulation signaling networks, but surprisingly, the majority of the genes identified are neither associated with innate or adaptive immunity nor associated with any antiviral activity. Confirmatory studies of eight of the genes validate the initial screening data. Mechanistic studies on TRIM7 demonstrated a conserved role of the molecule in mouse and human cells in restricting MNoV in a step of infection after viral entry. Furthermore, we demonstrate that two isoforms of TRIM7 have differential antiviral activity. Taken together, these data provide a resource for understanding norovirus biology and demonstrate a robust methodology for identifying new antiviral molecules.IMPORTANCE Norovirus is one of the leading causes of food-borne illness worldwide. Despite its prevalence, our understanding of norovirus biology is limited due to the difficulty in growing human norovirus in vitro and a lack of an animal model. Murine norovirus (MNoV) is a model norovirus system because MNoV replicates robustly in cell culture and in mice. To identify host genes that can restrict norovirus replication when overexpressed, we performed genome-wide CRISPR activation screens to induce gene overexpression at the native locus through recruitment of transcriptional activators to individual gene promoters. We found 49 genes that could block murine norovirus replication in human cells. Several of these genes are associated with classical immune signaling pathways, while many of the molecules we identified have not been previously associated with antiviral activity. Our data are a resource for those studying noroviruses, and we provide a robust approach to identify novel antiviral genes.
journal_name
J Viroljournal_title
Journal of virologyauthors
Orchard RC,Sullender ME,Dunlap BF,Balce DR,Doench JG,Virgin HWdoi
10.1128/JVI.01324-18subject
Has Abstractpub_date
2018-12-10 00:00:00issue
1eissn
0022-538Xissn
1098-5514pii
JVI.01324-18journal_volume
93pub_type
杂志文章abstract::Synthesis of the fiber protein of human adenovirus serotype 2 (Ad2) is 100-fold lower in abortively infected monkey cells, compared with productive infections, despite only a 5- to 10-fold reduction in fiber mRNA levels. Previously Anderson and Klessig (Proc. Natl. Acad Sci. USA 81:4023-4027, 1984) demonstrated a dire...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.10.4376-4385.1989
更新日期:1989-10-01 00:00:00
abstract::An immunocompetent, permissive, small-animal model would be valuable for the study of human immunodeficiency virus type 1 (HIV-1) pathogenesis and for the testing of drug and vaccine candidates. However, the development of such a model has been hampered by the inability of primary rodent cells to efficiently support s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01607-10
更新日期:2010-12-01 00:00:00
abstract::We have proposed a general algorithm for identification of potential immunoprotective domains (cassettes) on the envelope E2 polypeptide of alphaviruses (H. Grosfeld, B. Velan, M. Leitner, S. Cohen, S. Lustig, B.E. Lachmi, and A. Shafferman, J. Virol. 63:3416-3422, 1989). To assess the generality of our approach, we c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.1084-1090.1992
更新日期:1992-02-01 00:00:00
abstract::The virion host shutoff (vhs) protein encoded by herpes simplex virus type 1 (HSV-1) destabilizes both viral and host mRNAs. An HSV-1 strain with a mutation in vhs is attenuated in virulence and induces immune responses in mice that are protective against corneal infection with virulent HSV-1, but it has the capacity ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.23.11137-11144.2000
更新日期:2000-12-01 00:00:00
abstract::Human papillomavirus type 18 (HPV18) and HPV45 account for approximately 20% of all cervix cancers. We show that HPV18, HPV45, and the recently discovered HPV97 comprise a clade sharing a most recent common ancestor within HPV alpha7 species. Variant lineages of these HPV types were classified by sequence analysis of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02068-08
更新日期:2009-02-01 00:00:00
abstract::CD8+ T cells were previously shown to be important in preventing lymphoproliferation and immunodeficiency following infection of murine AIDS (MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia viruses. To further evaluate the mechanisms contributing to MAIDS resistance, we studied mice lacking CD8+ T cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.3.1808-1813.1997
更新日期:1997-03-01 00:00:00
abstract::We have previously shown for the paramyxovirus simian virus 5 (SV5) that a functional promoter for RNA replication requires proper spacing between two discontinuous elements: a 19-base segment at the 3' terminus (conserved region I [CRI]) and an 18-base internal region (CRII) that is contained within the coding region...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.8.3993-3998.2001
更新日期:2001-04-01 00:00:00
abstract::Infection of Escherichia coli with the satellite virus P4 without its helper bacteriophage P2 leads either to the immune integrated state or to the nonimmune multicopy plasmid condition. We analyzed the transcription pattern of the phage plasmid P4 early and late after infection and during the stable plasmid or lysoge...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.5.1697-1704.1988
更新日期:1988-05-01 00:00:00
abstract::Coronavirus subgenomic mRNA possesses a 5'-end leader sequence which is derived from the 5' end of genomic RNA and is linked to the mRNA body sequence. This study examined whether coronavirus transcription involves a discontinuous transcription step; the possibility that a leader sequence from mouse hepatitis virus (M...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2615-2623.1994
更新日期:1994-04-01 00:00:00
abstract::The susceptibility of monocyte-derived cultured dendritic cells (DCs) to human immunodeficiency virus (HIV) infection and their role in viral transmission in the immune response were studied in detail. We observed that highly purified cultured DCs were infected with the T-tropic Lai strain of HIV type 1 (HIV-1Lai) via...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.7.4544-4547.1995
更新日期:1995-07-01 00:00:00
abstract::Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01563-17
更新日期:2018-01-30 00:00:00
abstract::Influenza virus has a set of ribonucleoproteins (RNPs) consisting of viral RNAs, influenza virus polymerase subunits, and nucleoprotein. Intracellular reconstitution of the whole set of RNPs via plasmid transfection results in the generation of influenza virus. By the use of reverse genetics and dual promoters, we con...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00781-09
更新日期:2009-09-01 00:00:00
abstract::We analyzed peripheral blood mononuclear cells from 19 asymptomatic seropositive pregnant women from the district of Gulu in northern Uganda. A 700-bp fragment of the human immunodeficiency virus type 1 (HIV-1) env gene, including the V3-V5 region, was successfully amplified by PCR from 10 samples (52.6%) and was subs...
journal_title:Journal of virology
pub_type: 杂志文章,多中心研究
doi:10.1128/JVI.69.12.7971-7981.1995
更新日期:1995-12-01 00:00:00
abstract::Major histocompatibility complex class I (MHC I)-restricted CD8(+) T-cell responses play a pivotal role in anti-human immunodeficiency virus (HIV) immunity and the control of viremia. The rhesus macaque is an important animal model for HIV-related research. Among the MHC I alleles of the rhesus macaque, Mamu-A 02 is p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00350-11
更新日期:2011-07-01 00:00:00
abstract:UNLABELLED:HIV-1-specific CD8 T cells can influence HIV-1 disease progression during untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1-specific CD8 T cells in individuals treated with suppressive antiretroviral therapy remain less well understood. Here we show that a subgroup of HIV-1-spe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00789-15
更新日期:2015-08-01 00:00:00
abstract::Under natural conditions and in some experimental models, rabies virus infection of the central nervous system causes relatively mild histopathological changes, without prominent evidence of neuronal death despite its lethality. In this study, the effects of rabies virus infection on the structure of neurons were inve...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01677-07
更新日期:2008-01-01 00:00:00
abstract::Replication of the Epstein-Barr virus genome initiates at one of several sites in latently infected, dividing cells. One of these replication origins is close to the viral DNA maintenance element, and, together, this replication origin and the maintenance element are referred to as oriP. The replicator of oriP contain...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.22.10582-10592.2001
更新日期:2001-11-01 00:00:00
abstract::The DNA molecules from T7 bacteriophage and a recently obtained mutant form of T4D were studied. The DNA of this T4 mutant contains cytosine in place of all of the glucosylated hydroxymethylcytosines normally present in T4. Molecular weights were measured with an electron microscope technique, and sedimentation coeffi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.33.1.438-448.1980
更新日期:1980-01-01 00:00:00
abstract::Polyamine depletion produced by exogenous arginine in Escherichia coliK-12 cultures defective in agmatine ureohydrolase activity resulted in a marked inhibition of the rates of growth and nucleic acid synthesis. Addition of putrescine or spermidine to such depleted cultures restored the control rate of growth and nucl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.3.423-430.1972
更新日期:1972-03-01 00:00:00
abstract::The cellular requirements for activation of herpesvirus fusion and entry remain poorly understood. Low pH triggers change in the antigenic reactivity of the prefusion form of the herpes simplex virus (HSV) fusion protein gB in virions, both in vitro and during viral entry via endocytosis (S. Dollery et al., J. Virol. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05291-11
更新日期:2011-10-01 00:00:00
abstract::The purified T-antigen origin binding domain binds site specifically to site II, the central region of the simian virus 40 core origin. However, in the context of full-length T antigen, the origin binding domain interacts poorly with DNA molecules containing just site II. Here we investigate the contributions of addit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.6.2921-2934.2004
更新日期:2004-03-01 00:00:00
abstract::When Epstein-Barr virus (EBV) negative cells (Raji) were treated with iododeoxyuridine, only the early antigen (EA) component was induced. There was no significant increase in EBV DNA and no virus particles were observed. Somatic-cell hybrids were prepared from the fusion of Raji and D98 cells (D98/Raji). When these c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.1.174-176.1974
更新日期:1974-07-01 00:00:00
abstract::The beginning of the second century of research in the field of virology (the first virus was discovered in 1898) was marked by its amalgamation with bioinformatics, resulting in the birth of a new domain--viroinformatics. The availability of more than 100 Web servers and databases embracing all or specific viruses (f...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.02027-14
更新日期:2015-02-01 00:00:00
abstract::RNA viruses within a host exist as dynamic distributions of closely related mutants and recombinant genomes. These closely related mutants and recombinant genomes, which are subjected to a continuous process of genetic variation, competition, and selection, act as a unit of selection, termed viral quasispecies. Charac...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00950-09
更新日期:2009-12-01 00:00:00
abstract::We have generated hexon-modified adenovirus serotype 5 (Ad5) vectors that are not neutralized by Ad5-specific neutralizing antibodies in mice. These vectors are attractive for the advancement of vaccine products because of their potential for inducing robust antigen-specific immune responses in people with prior expos...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00462-13
更新日期:2013-09-01 00:00:00
abstract::The simian virus 40 large T antigen is a promiscuous transcriptional activator of many viral and cellular promoters. We show that the promoter structure necessary for T antigen-mediated transcriptional activation is very simple. A TATA or initiator element is required, in addition to an upstream factor-binding site, w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.11.6682-6688.1993
更新日期:1993-11-01 00:00:00
abstract::A single phosphorylation event at T-antigen residue Thr124 regulates initiation of simian virus 40 DNA replication. To explore this regulatory process, a series of peptides were synthesized, centered on Thr124. These peptides contain a nuclear localization signal (NLS) and a recognition site for cyclin/Cdk kinases. Wh...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.23.11785-11792.2002
更新日期:2002-12-01 00:00:00
abstract::Replication of the genomic RNA of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by replicase polyproteins that are processed by two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro). Previously, we showed that SARS-CoV PLpro processes the replicase polyprotein at three ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.24.15189-15198.2005
更新日期:2005-12-01 00:00:00
abstract:UNLABELLED:Based on an explant reactivation model, it has been proposed that CD8(+) T cells maintain latency in trigeminal ganglia (TG) of mice latently infected with herpes simplex virus 1 (HSV-1) [T. Liu, K. M. Khanna, X. Chen, D. J. Fink, and R. L. Hendricks, J Exp Med 191:1459-1466, 2000, doi:10.1084/jem.191.9.1459...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00255-16
更新日期:2016-04-29 00:00:00
abstract::A high prevalence (42.6%) of hepatitis B virus (HBV) infection was suspected in 195 formerly captive orangutans due to a large number of serum samples which cross-reacted with human HBV antigens. It was assumed that such viral infections were contracted from humans during captivity. However, two wild orangutans were i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.9.7860-7865.1999
更新日期:1999-09-01 00:00:00