Enhancement of antiviral activity of human alpha-defensin 5 against herpes simplex virus 2 by arginine mutagenesis at adaptive evolution sites.

Abstract:

:Herpes simplex virus 2 (HSV-2) infection is still one of the common causes of sexually transmitted diseases worldwide. The prevalence of HSV strains resistant to traditional nucleoside antiviral agents has led to the development of novel antiviral drugs. Human alpha-defensin 5 (HD5), a kind of endogenous antimicrobial peptide expressed in the epithelia of the small intestine and urogenital tract, displays natural antiviral activity. Based on arginine-rich features and adaptive evolution characteristics of vertebrate defensins, we conducted a screen for HD5 derivatives with enhanced anti-HSV-2 activity by a single arginine substitution at the adaptive evolution sites. Cell protection assay and temporal antiviral studies showed that HD5 and its mutants displayed affirmatory but differential anti-HSV-2 effects in vitro by inhibiting viral adhesion and entry. Inspiringly, the E21R-HD5 mutant had significantly higher antiviral activity than natural HD5, which is possibly attributed to the stronger binding affinity of the E21R-HD5 mutant with HSV-2 capsid protein gD, indicating that E21R mutation can increase the anti-HSV-2 potency of HD5. In a mouse model of lethal HSV-2 infection, prophylactic and/or therapeutic treatment with E21R-HD5 via intravaginal instillation remarkably alleviated the symptoms and delayed disease progress and resulted in about a 1.5-fold-higher survival rate than in the HD5 group. Furthermore, the E21R variant exhibited a 2-fold-higher antiviral potency against HIV-1 over parental HD5 in vitro. This study demonstrates that arginine mutagenesis at appropriate evolution sites may significantly enhance the antiviral activity of HD5, which also paves a facile way to search for potent antiviral drugs based on natural antimicrobial peptides.

journal_name

J Virol

journal_title

Journal of virology

authors

Wang A,Chen F,Wang Y,Shen M,Xu Y,Hu J,Wang S,Geng F,Wang C,Ran X,Su Y,Cheng T,Wang J

doi

10.1128/JVI.02209-12

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

2835-45

issue

5

eissn

0022-538X

issn

1098-5514

pii

JVI.02209-12

journal_volume

87

pub_type

杂志文章
  • Vaccine protection against simian immunodeficiency virus by recombinant strains of herpes simplex virus.

    abstract::An effective vaccine for AIDS may require development of novel vectors capable of eliciting long-lasting immune responses. Here we report the development and use of replication-competent and replication-defective strains of recombinant herpes simplex virus (HSV) that express envelope and Nef antigens of simian immunod...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.17.7745-7754.2000

    authors: Murphy CG,Lucas WT,Means RE,Czajak S,Hale CL,Lifson JD,Kaur A,Johnson RP,Knipe DM,Desrosiers RC

    更新日期:2000-09-01 00:00:00

  • Replication of macrophage-tropic and T-cell-tropic strains of human immunodeficiency virus type 1 is augmented by macrophage-endothelial cell contact.

    abstract::Macrophages perform a central role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection and have been implicated as the cell type most prominent in the development of central nervous system impairment. In this study, we evaluated the effect of interaction between macrophages and endothelial cel...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.69.4.2133-2139.1995

    authors: Gilles PN,Lathey JL,Spector SA

    更新日期:1995-04-01 00:00:00

  • Role of the sonchus yellow net virus N protein in formation of nuclear viroplasms.

    abstract::Sonchus yellow net virus is a plant nucleorhabdovirus whose nucleocapsid (N), phosphoprotein (P), and polymerase (L) proteins form large viroplasms in the nuclei of infected plants (C. R. F. Martins, J. A. Johnson, D. M. Lawrence, T. J. Choi, A. Pisi, S. L. Tobin, D. Lapidus, J. D. O. Wagner, S. Ruzin, K. McDonald, an...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02349-06

    authors: Deng M,Bragg JN,Ruzin S,Schichnes D,King D,Goodin MM,Jackson AO

    更新日期:2007-05-01 00:00:00

  • Replication-competent herpes simplex virus 1 isolates selected from cells transfected with a bacterial artificial chromosome DNA lacking only the UL49 gene vary with respect to the defect in the UL41 gene encoding host shutoff RNase.

    abstract::To generate a null U(L)49 gene mutant of herpes simplex virus 1 (HSV-1), we deleted from the viral DNA, encoded as a bacterial artificial chromosome (BAC), the U(L)49 open reading frame and, in a second step, restored it. Upon transfection into Vero cells, the BAC-DeltaU(L)49 DNA yielded foci of degenerated cells that...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01239-07

    authors: Sciortino MT,Taddeo B,Giuffrè-Cuculletto M,Medici MA,Mastino A,Roizman B

    更新日期:2007-10-01 00:00:00

  • Biochemical characterization of the type C retrovirus associated with lymphoproliferative disease of turkeys.

    abstract::Turkeys inoculated with spleen extracts from lymphoproliferative disease (LPD)-affected birds developed viremia, followed by typical LPD lesions. Electron microscopy and biochemical characterization established that the virus present in the blood of infected turkeys is a type C retrovirus. The viral particles possess ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.30.1.351-357.1979

    authors: Yaniv A,Gazit A,Ianconescu M,Perk K,Aizenberg B,Zimber A

    更新日期:1979-04-01 00:00:00

  • Reovirus M2 gene is associated with chromium release from mouse L cells.

    abstract::In this study, we investigated the interaction of reovirus particles with cell membranes by using a 51Cr release assay. We confirmed prior observations (J. Borsa, B. D. Morash, M. D. Sargent, T. P. Copps, P. A. Lievaart, and J. G. Szekely, J. Gen. Virol. 45:161-170, 1979) that intermediate subviral particles (ISVPs) o...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.67.9.5339-5345.1993

    authors: Lucia-Jandris P,Hooper JW,Fields BN

    更新日期:1993-09-01 00:00:00

  • The concentration of Ca2+ that solubilizes outer capsid proteins from rotavirus particles is dependent on the strain.

    abstract::It has been previously shown that rotavirus maturation and stability of the outer capsid are calcium-dependent processes. More recently, it has been hypothesized that penetration of the cell membrane is also affected by conformational changes of the capsid induced by Ca2+. In this study, we determined quantitatively t...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.8.4877-4883.1996

    authors: Ruiz MC,Charpilienne A,Liprandi F,Gajardo R,Michelangeli F,Cohen J

    更新日期:1996-08-01 00:00:00

  • Structural proteins of rabies virus.

    abstract::Purified rabies virions, unlabeled or labeled with radioactive amino acids or d-glucosamine, were dissociated into their polypeptides by treatment with sodium dodecyl sulfate in a reducing environment and fractionated by electroiphoresis in sodium dodecyl sulfate-containing polyacrylamide gel. The molecular weights of...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.7.2.241-249.1971

    authors: Sokol F,Stancek D,Koprowski H

    更新日期:1971-02-01 00:00:00

  • Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage.

    abstract::Hemorrhage is a common clinical manifestation in dengue patients. However, the pathogenic mechanism of dengue virus (DV)-induced hemorrhage awaits clarification. We established a mouse model of DV hemorrhage using immunocompetent C57BL/6 mice by injecting DV serotype 2 strain 16681 intradermally. While inoculation of ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02575-06

    authors: Chen HC,Hofman FM,Kung JT,Lin YD,Wu-Hsieh BA

    更新日期:2007-06-01 00:00:00

  • Cloning of an avian adeno-associated virus (AAAV) and generation of recombinant AAAV particles.

    abstract::Recent studies have proposed that adeno-associated viruses (AAVs) are not evolutionarily linked to other mammalian autonomous parvoviruses but are more closely linked to the autonomous parvoviruses of birds. To better understand the relationship between primate and avian AAVs (AAAVs), we cloned and sequenced the genom...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.77.12.6799-6810.2003

    authors: Bossis I,Chiorini JA

    更新日期:2003-06-01 00:00:00

  • RNA recombination in vivo in the absence of viral replication.

    abstract::To study fundamental aspects of RNA recombination, an in vivo RNA recombination system was established. This system allowed the efficient generation of recombinant cytopathogenic pestiviruses after transfection of synthetic, nonreplicatable, subgenomic transcripts in cells infected with a replicating noncytopathogenic...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.12.6271-6281.2004

    authors: Gallei A,Pankraz A,Thiel HJ,Becher P

    更新日期:2004-06-01 00:00:00

  • Early steps of polyomavirus entry into cells.

    abstract::The mechanism by which murine polyomavirus penetrates cells and arrives at the nucleus, the site of viral replication, is not well understood. Simian virus 40 and JC virus, two closely related members of the polyomavirus subfamily, use caveola- and clathrin-mediated uptake pathways for entry, respectively. The data pr...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.18.8582-8588.2000

    authors: Gilbert JM,Benjamin TL

    更新日期:2000-09-01 00:00:00

  • Strain-specific barriers against bovine prions in hamsters.

    abstract::We investigated the susceptibilities of Syrian golden hamsters to transmissible spongiform encephalopathy agents from cattle. We report efficient transmission of the L-type atypical bovine spongiform encephalopathy (BSE) agent into hamsters. Importantly, hamsters were also susceptible to the transmissible mink encepha...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01872-10

    authors: Nicot S,Baron T

    更新日期:2011-02-01 00:00:00

  • Evolutionary genetics of human enterovirus 71: origin, population dynamics, natural selection, and seasonal periodicity of the VP1 gene.

    abstract::Human enterovirus 71 (EV-71) is one of the major etiologic causes of hand, foot, and mouth disease (HFMD) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. Global VP1 capsid sequences (n = 628) sampled over 4 decades were collected and subjected to compreh...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01019-09

    authors: Tee KK,Lam TT,Chan YF,Bible JM,Kamarulzaman A,Tong CY,Takebe Y,Pybus OG

    更新日期:2010-04-01 00:00:00

  • Biophysical and biochemical characterization of five animal viruses with bisegmented double-stranded RNA genomes.

    abstract::Infectious pancreatic necrosis virus of fish, infectious bursal disease virus of chickens, Tellina virus and oyster virus of bivalve molluscs, and drosophila X virus of Drosophila melanogaster are naked icosahedral viruses with an electron microscopic diameter of 58 to 60 nm. The genome of each of these viruses consis...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.32.2.593-605.1979

    authors: Dobos P,Hill BJ,Hallett R,Kells DT,Becht H,Teninges D

    更新日期:1979-11-01 00:00:00

  • The herpes simplex virus type 1 U(S)11 protein interacts with protein kinase R in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain.

    abstract::The herpes simplex virus type 1 gamma(1)34.5 gene product precludes the host-mediated protein shutoff response induced by activated protein kinase R (PKR). Earlier studies demonstrated that recombinant viruses lacking the gamma(1)34.5 gene (Deltagamma(1)34.5) developed secondary mutations that allowed earlier U(S)11 e...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.76.5.2029-2035.2002

    authors: Cassady KA,Gross M

    更新日期:2002-03-01 00:00:00

  • Complex formation of human T-cell leukemia virus type I p40tax transactivator with cellular polypeptides.

    abstract::We examined cellular components which associate with p40tax, the viral transactivation molecule of human T-cell leukemia virus type I. Such molecules were searched by immunoprecipitation with polyclonal and monoclonal antibodies specific for p40tax. Two cellular proteins with molecular masses of 95 kDa (p95) and 60 kD...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.66.2.1040-1049.1992

    authors: Nagata K,Ide Y,Takagi T,Ohtani K,Aoshima M,Tozawa H,Nakamura M,Sugamura K

    更新日期:1992-02-01 00:00:00

  • Macromolecular Synthesis Shutoff Resistance by Myeloid Cells Is Critical to IRF7-Dependent Systemic Interferon Alpha/Beta Induction after Alphavirus Infection.

    abstract::Alphavirus infection of fibroblastic cell types in vitro inhibits host cell translation and transcription, leading to suppression of interferon alpha/beta (IFN-α/β) production. However, the effect of infection upon myeloid cells, which are often the first cells encountered by alphaviruses in vivo, is unclear. Previous...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00872-19

    authors: Bhalla N,Gardner CL,Downs SN,Dunn M,Sun C,Klimstra WB

    更新日期:2019-11-26 00:00:00

  • Insertion of capsid proteins from nonenveloped viruses into the retroviral budding pathway.

    abstract::Retroviral Gag proteins direct the assembly and release of virus particles from the plasma membrane. The budding machinery consists of three small domains, the M (membrane-binding), I (interaction), and L (late or "pinching-off") domains. In addition, Gag proteins contain sequences that control particle size. For Rous...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.75.14.6527-6536.2001

    authors: Krishna NK,Wills JW

    更新日期:2001-07-01 00:00:00

  • Ubiquitination of human T-cell leukemia virus type 1 tax modulates its activity.

    abstract::Human T-cell leukemia virus type 1 (HTLV-1) encodes a 40-kDa Tax phosphoprotein. Tax is a transcriptional activator which modulates expression of the viral long terminal repeat and transcription of many cellular genes. Because Tax is a critical HTLV-1 factor which mediates viral transformation of T cells during the ge...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.21.11686-11695.2004

    authors: Peloponese JM Jr,Iha H,Yedavalli VR,Miyazato A,Li Y,Haller K,Benkirane M,Jeang KT

    更新日期:2004-11-01 00:00:00

  • Temperature-dependent host range mutation in vesicular stomatitis virus affecting polypeptide L.

    abstract::We established previously that the temperature-dependent host range mutant, td CE 3, of vesicular stomatitis virus (VSV) New Jersey possesses temperature-sensitive RNA transcriptase activity. In this paper, we describe dissociation and reconstitution experiments designed to determine which VSV polypeptide is affected ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.22.2.381-388.1977

    authors: Szilágyi JF,Pringle CR,Macpherson TM

    更新日期:1977-05-01 00:00:00

  • A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation.

    abstract::Latency-associated transcript (LAT) promoter deletion mutants of herpes simplex virus type 1 have a reduced capacity to reactivate following adrenergic induction in the rabbit eye model. We have mapped a reactivation phenotype within LAT and describe the construction of recombinants in which poly(A) addition sites hav...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.4.2449-2459.1996

    authors: Bloom DC,Hill JM,Devi-Rao G,Wagner EK,Feldman LT,Stevens JG

    更新日期:1996-04-01 00:00:00

  • The transmembrane domain of the respiratory syncytial virus F protein is an orientation-independent apical plasma membrane sorting sequence.

    abstract::The processes that facilitate transport of integral membrane proteins though the secretory pathway and subsequently target them to particular cellular membranes are relevant to almost every field of biology. These transport processes involve integration of proteins into the membrane of the endoplasmic reticulum (ER), ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.19.12528-12535.2005

    authors: Brock SC,Heck JM,McGraw PA,Crowe JE Jr

    更新日期:2005-10-01 00:00:00

  • Structure of Bacillus subtilis bacteriophage phi25 and phi25 deoxyribonucleic acid.

    abstract::The structure of Bacillus subtilis bacteriophage phi25 and phi25 deoxyribonucleic acid (DNA) were studied by electron microscopy. The head of phi25 is a regular polyhedron measuring 75 nm in diameter. The uncontracted tail of phi25 is 130 nm in length and includes a large, complex tail plate. Phage phi25 DNA is double...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.6.1.107-113.1970

    authors: Liljemark WF,Anderson DL

    更新日期:1970-07-01 00:00:00

  • Identification of amino acids involved in recognition by dengue virus NS3-specific, HLA-DR15-restricted cytotoxic CD4+ T-cell clones.

    abstract::The majority of T-cell clones derived from a donor who experienced dengue illness following receipt of a live experimental dengue virus type 3 (DEN3) vaccine cross-reacted with all four serotypes of dengue virus, but some were serotype specific or only partially cross-reactive. The nonstructural protein, NS3, was immu...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.5.3108-3117.1996

    authors: Zeng L,Kurane I,Okamoto Y,Ennis FA,Brinton MA

    更新日期:1996-05-01 00:00:00

  • Inhibition of interferon signaling by the Kaposi's sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein.

    abstract::Interferon (IFN) signal transduction involves interferon regulatory factors (IRF). Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four IRF homologues: viral IRF 1 (vIRF-1) to vIRF-4. Previous functional studies revealed that the first exon of vIRF-2 inhibited alpha/beta interferon (IFN-alpha/beta) signaling. W...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.6.3092-3097.2006

    authors: Fuld S,Cunningham C,Klucher K,Davison AJ,Blackbourn DJ

    更新日期:2006-03-01 00:00:00

  • Viral phenotypes and antibody responses in long-term survivors infected with attenuated human immunodeficiency virus type 1 containing deletions in the nef and long terminal repeat regions.

    abstract::The Sydney Blood Bank Cohort (SBBC) consists of eight blood transfusion recipients infected with nef-attenuated human immunodeficiency virus type 1 (HIV-1) acquired from a single donor. Here, we show that viral phenotypes and antibody responses differ considerably between individual cohort members, despite the single ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00650-07

    authors: Verity EE,Zotos D,Wilson K,Chatfield C,Lawson VA,Dwyer DE,Cunningham A,Learmont J,Dyer W,Sullivan J,Churchill M,Wesselingh SL,Gabuzda D,Gorry PR,McPhee DA

    更新日期:2007-09-01 00:00:00

  • Nonsense mutation in open reading frame E2 of bovine papillomavirus DNA.

    abstract::Oligonucleotide-directed mutagenesis was used to construct a nonsense mutation in open reading frame (ORF) E2 of bovine papillomavirus DNA. A single base substitution mutation was constructed which converted a TAC codon into a TAG amber stop codon at a position in the ORF that did not overlap with any other viral ORFs...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.57.2.475-480.1986

    authors: DiMaio D

    更新日期:1986-02-01 00:00:00

  • Pol-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells prior to Nef-mediated major histocompatibility complex class I downregulation.

    abstract::Effective, vaccine-induced CD8+ T-cell responses should recognize infected cells early enough to prevent production of progeny virions. We have recently shown that Gag-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells at 2 h postinfection, whereas Env-specific CD8+ T cells do not recognize i...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00926-07

    authors: Sacha JB,Chung C,Reed J,Jonas AK,Bean AT,Spencer SP,Lee W,Vojnov L,Rudersdorf R,Friedrich TC,Wilson NA,Lifson JD,Watkins DI

    更新日期:2007-11-01 00:00:00

  • WITHDRAWN: Natural recombination between Newcastle disease virus vaccine strains and circulating viruses.

    abstract::This article has been retracted. ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01824-07

    authors: He CQ,Ding NZ,Han GZ,Liu W

    更新日期:2008-01-23 00:00:00