Abstract:
:Polyamides have been shown to bind double-stranded DNA by complementing the curvature of the minor groove and forming various hydrogen bonds with DNA. Several polyamide molecules have been found to have potent antiviral activities against papillomavirus, a double-stranded DNA virus. By analogy, we reason that polyamides may also interact with the structured RNA bound in the nucleocapsid of a negative-strand RNA virus. Vesicular stomatitis virus (VSV) was selected as a prototype virus to test this possibility since its genomic RNA encapsidated in the nucleocapsid forms a structure resembling one strand of an A-form RNA duplex. One polyamide molecule, UMSL1011, was found to inhibit infection of VSV. To confirm that the polyamide targeted the nucleocapsid, a nucleocapsid-like particle (NLP) was incubated with UMSL1011. The encapsidated RNA in the polyamide-treated NLP was protected from thermo-release and digestion by RNase A. UMSL1011 also inhibits viral RNA synthesis in the intracellular activity assay for the viral RNA-dependent RNA polymerase. The crystal structure revealed that UMSL1011 binds the structured RNA in the nucleocapsid. The conclusion of our studies is that the RNA in the nucleocapsid is a viable antiviral target of polyamides. Since the RNA structure in the nucleocapsid is similar in all negative-strand RNA viruses, polyamides may be optimized to target the specific RNA genome of a negative-strand RNA virus, such as respiratory syncytial virus and Ebola virus.IMPORTANCE Negative-strand RNA viruses (NSVs) include several life-threatening pathogens, such as rabies virus, respiratory syncytial virus, and Ebola virus. There are no effective antiviral drugs against these viruses. Polyamides offer an exceptional opportunity because they may be optimized to target each NSV. Our studies on vesicular stomatitis virus, an NSV, demonstrated that a polyamide molecule could specifically target the viral RNA in the nucleocapsid and inhibit viral growth. The target specificity of the polyamide molecule was proved by its inhibition of thermo-release and RNA nuclease digestion of the RNA bound in a model nucleocapsid, and a crystal structure of the polyamide inside the nucleocapsid. This encouraging observation provided the proof-of-concept rationale for designing polyamides as antiviral drugs against NSVs.
journal_name
J Viroljournal_title
Journal of virologyauthors
Gumpper RH,Li W,Castañeda CH,Scuderi MJ,Bashkin JK,Luo Mdoi
10.1128/JVI.00146-18subject
Has Abstractpub_date
2018-03-28 00:00:00issue
8eissn
0022-538Xissn
1098-5514pii
JVI.00146-18journal_volume
92pub_type
杂志文章abstract::An assay to identify interactions between Citrus Dwarfing Viroid (CDVd) and Citrus Tristeza Virus (CTV) showed that viroid titer was enhanced by the coinfecting CTV in Mexican lime but not in etrog citron. Since CTV encodes three RNA silencing suppressors (RSSs), p23, p20 and p25, an assay using transgenic Mexican lim...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02619-13
更新日期:2014-01-01 00:00:00
abstract::Poliovirus has been studied as a live recombinant vaccine vector because of its attractive characteristics. The genetic instability, however, has hampered recombinant polioviruses (PVs) from being developed as an appropriate vaccine. A variety of different foreign inserts were cloned directly into our poliovirus Sabin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.4.1649-1662.2002
更新日期:2002-02-01 00:00:00
abstract::In cytomegalovirus-infected cells, the rate of protein synthesis was detected as two peaks. One occurred during the early phase of infection, 0 to 36 h postinfection, and the other occurred during the late phase, after the initiation of viral DNA synthesis. Double-isotopic-label difference analysis demonstrated that h...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.23.3.751-767.1977
更新日期:1977-09-01 00:00:00
abstract::Recent evidence supports a role for vitamin K-dependent coagulation zymogens in adenovirus serotype 5 (Ad5, subgroup C) infection of hepatocytes. Here, we assessed the effect of virus-zymogen interaction on cellular transduction using a panel of fiber (f)-pseudotyped viruses derived from subgroup D (f47, f33, f24, f45...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02786-06
更新日期:2007-04-01 00:00:00
abstract::Human bocavirus (HBoV) is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI) and gastrointestinal illness. No previous reports indicated the presence of HBoV infection in Jiangsu Province, China. Here we report three complete genomic sequences of HBoV strains from children with gastro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02618-12
更新日期:2012-12-01 00:00:00
abstract::The expression of interleukin-2 (IL-2) has been implicated in the modulation of the outcome of ocular infection with herpes simplex virus type 1 (HSV-1); however, its effects remain controversial. To clarify the role of IL-2, we constructed a recombinant HSV-1 (HSV-IL-2) that expresses two copies of the murine IL-2 ge...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.18.9069-9078.2002
更新日期:2002-09-01 00:00:00
abstract::Transfection of an Epstein-Barr virus (EBV)-encoded plasmid containing EBER caused a substantial decrease in the level of plasmid containing EBV in Akata and Mutu Burkitt's lymphoma (BL) lines, but failed to do so in other BL lines. The results suggest that EBER could replace the role of EBV, but other EBV products al...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.20.9977-9982.2001
更新日期:2001-10-01 00:00:00
abstract::The cytopathic effect (CPE) seen with some subgroups of avian sarcoma and leukosis virus (ASLV) is associated with viral Env activation of the death-promoting activity of TVB (a tumor necrosis factor receptor-related receptor that is most closely related to mammalian TNF-related apoptosis-inducing ligand [TRAIL] recep...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.13.8243-8248.2005
更新日期:2005-07-01 00:00:00
abstract::Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. The hyperglycosylated hemagglutinin enhance...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02608-13
更新日期:2014-01-01 00:00:00
abstract::Two virus-specific species of newly synthesized DNA were isolated from rat fibroblast cell cultures infected with the Kilham rat virus (RV). These two DNA species were purified; their behavior on hydroxyapatite chromatography and their sedimentation coefficients in sucrose gradients were determined. One of the two spe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.20.1.86-95.1976
更新日期:1976-10-01 00:00:00
abstract::We have presented a new approach to studying bacteriophage T4 head maturation. Using a modified M-band technique, we have shown that progeny deoxyribonucleic acid (DNA) was synthesized on the host cell membrane throughout infection. This DNA was released from the membrane later in infection as the result of formation ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.11.3.359-367.1973
更新日期:1973-03-01 00:00:00
abstract::Recently, we demonstrated that inverted repeat sequences inserted into first-generation adenovirus (Ad) vector genomes mediate precise genomic rearrangements resulting in vector genomes devoid of all viral genes that are efficiently packaged into functional Ad capsids. As a specific application of this finding, we gen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9314-9324.1999
更新日期:1999-11-01 00:00:00
abstract::Retroviruses have been isolated from the tissues of human leukemia patients. Previous studies have shown that these isolates share some antigenic determinants with the family of viruses isolated from the woolly monkey and gibbon ape and that they exhibit partial nuclei acid homology with this same group of viruses. We...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.34.2.390-401.1980
更新日期:1980-05-01 00:00:00
abstract::MicroRNAs (miRNAs) are key regulators of gene expression in higher eukaryotes. Recently, miRNAs have been identified from viruses with double-stranded DNA genomes. To attempt to identify miRNAs encoded by herpes simplex virus 1 (HSV-1), we applied a computational method to screen the complete genome of HSV-1 for seque...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00200-06
更新日期:2006-06-01 00:00:00
abstract::West Nile virus (WNV), currently the cause of a serious U.S. epidemic, is a mosquito-borne flavivirus and member of the Japanese encephalitis (JE) serocomplex. There is currently no approved human WNV vaccine, and treatment options remain limited, resulting in significant mortality and morbidity from human infection. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00480-13
更新日期:2013-09-01 00:00:00
abstract::Respiratory syncytial (RS) virus infects the epithelium of the respiratory tract. We examined the replication and maturation of RS virus in two polarized epithelial cell lines, Vero C1008 and MDCK. Electron microscopy of RS virus-infected Vero C1008 cells revealed the presence of pleomorphic viral particles budding ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2667-2673.1995
更新日期:1995-04-01 00:00:00
abstract:UNLABELLED:Molluscum contagiosum virus (MOCV), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months in young children and severe infections in immunosuppressed adults. Studies of MOCV are restricted by the lack of an efficient animal model...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02911-15
更新日期:2016-04-14 00:00:00
abstract::Primary HIV-1 infection (PHI) is marked by a flu-like syndrome and high levels of viremia that decrease to a viral set point with the first emergence of virus-specific CD8+ T-cell responses. Here, we investigated in a large cohort of 527 subjects the immunodominance pattern of the first virus-specific cytotoxic T-lymp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00182-09
更新日期:2009-08-01 00:00:00
abstract::Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes disease in cattle populations worldwide. Sphingomyelin (SM) is the most abundant sphingolipid in the mammalian cell membrane, where it preferentially associates with cholesterol to form lipid raft domains. SM is a substrate for the lysosome-resident enzy...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01547-18
更新日期:2019-02-19 00:00:00
abstract::Two essential gene products of herpes simplex virus type 1, the viral DNA polymerase (pol) and UL42, its accessory protein, physically and functionally interact to form the core of the viral DNA replication complex. Understanding this essential interaction would provide a basis from which to develop novel anti-herpesv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.5922-5931.1993
更新日期:1993-10-01 00:00:00
abstract::Previous studies have suggested that coxsackievirus B (CVB) activates CD8(+) T cells in vivo, but the extent of this activation and the antigen specificity of the CD8(+) T cells remain uncertain. Furthermore, CVB-induced CD4(+) T-cell responses have not been carefully investigated. Herein, we evaluate CD8(+) and CD4(+...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02639-07
更新日期:2008-05-01 00:00:00
abstract::Lethal, amber mutations in T4 genes 46 and 47 cause incomplete degradation of host DNA, premature arrest of phage DNA synthesis, accumulation of abnormal DNA replication intermediates, and defective recombination. These phenotypes can be explained by the hypothesis that genes 46 and 47 control a DNA exonuclease, but i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.1.65-77.1981
更新日期:1981-10-01 00:00:00
abstract::The prevailing hypothesis is that the intracellular site of budding of coronaviruses is determined by the localization of its membrane protein M (previously called E1). We tested this by analyzing the site of budding of four different coronaviruses in relation to the intracellular localization of their M proteins. Mou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.10.6523-6534.1994
更新日期:1994-10-01 00:00:00
abstract::Most patients infected with hepatitis C virus (HCV) become chronic carriers. Viruses that efficiently establish persistent infections must have effective ways of evading host defenses. In the case of HCV, little is known about how chronic infections are established or maintained. Besides hepatocytes, several reports s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.2.772-781.2001
更新日期:2001-01-01 00:00:00
abstract::In addition to encoding the structural and regulatory proteins, many viruses encode auxiliary proteins, some of which have been shown to play important roles in lytic and latent states of the viruses. The human neurotropic JC virus (JCV) genome encodes an auxiliary protein called Agno whose function remains unknown. H...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.3.1476-1486.2001
更新日期:2001-02-01 00:00:00
abstract::Elite controllers (EC) of human immunodeficiency virus type 1 (HIV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8(+) T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02459-08
更新日期:2009-04-01 00:00:00
abstract::Mammalian cells infected with herpes simplex virus (HSV) express a novel ribonucleotide reductase which is biochemically and immunologically distinct from the uninfected-cell enzyme. Using polyvalent rabbit antiserum raised against partially purified HSV type 2 reductase as well as monoclonal antibodies to HSV type 1 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.591-593.1984
更新日期:1984-02-01 00:00:00
abstract:UNLABELLED:Many murine leukemia viruses (MLVs) are partially resistant to restriction by mouse APOBEC3 (mA3) and essentially fully resistant to induction of G-to-A mutations by mA3. In contrast, Vif-deficient HIV-1 (ΔVif HIV-1) is profoundly restricted by mA3, and the restriction includes high levels of G-to-A mutation...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03456-13
更新日期:2014-04-01 00:00:00
abstract::We have examined EcoRI-restricted cellular DNA from BALB/c mouse-hamster somatic cell hybrids by blot hybridization for the presence of mouse mammary tumor virus-related sequences. Results of this analysis show that mouse mammary tumor virus-related proviral copies are located on chromosomes 16 (16-kilobase-pair fragm...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.3.1005-1008.1984
更新日期:1984-03-01 00:00:00
abstract::A member of the family Circoviridae, porcine circovirus type 2 (PCV2), is associated with postweaning multisystemic wasting syndrome (PMWS), a recent emerging disease worldwide. PCV2 is also found in clinically asymptomatic animals. This paradoxical finding makes the syndrome etiology challenging. We developed new ass...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05156-11
更新日期:2011-11-01 00:00:00