Durable protection from Herpes Simplex Virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene.


:A vaginal microbicide should prevent pathogen transmission without disrupting tissue barriers to infection. Ideally, it would not need to be applied immediately before sexual intercourse, when compliance is a problem. Intravaginal administration of small interfering RNA (siRNA) lipoplexes targeting Herpes Simplex Virus Type 2 (HSV-2) genes protects mice from HSV-2. However, protection is short-lived, and the transfection lipid on its own unacceptably enhances transmission. Here, we show that cholesterol-conjugated (chol)-siRNAs without lipid silence gene expression in the vagina without causing inflammation or inducing interferons. A viral siRNA prevents transmission within a day of challenge, whereas an siRNA targeting the HSV-2 receptor nectin-1 protects for a week, but protection is delayed for a few days until the receptor is downmodulated. Combining siRNAs targeting a viral and host gene protects mice from HSV-2 for a week, irrespective of the time of challenge. Therefore, intravaginal siRNAs could provide sustained protection against viral transmission.


Cell Host Microbe


Cell host & microbe


Wu Y,Navarro F,Lal A,Basar E,Pandey RK,Manoharan M,Feng Y,Lee SJ,Lieberman J,Palliser D




Has Abstract


2009-01-22 00:00:00














  • The blessings and curses of intestinal inflammation.

    abstract::The intestinal immune system has to strike a delicate balance between initiating inflammatory responses against invading bacterial pathogens and avoiding their induction against microbiota colonizing the lumen. Adequate inflammatory responses against bacterial invasion result in the lumenal secretion of antimicrobial ...

    journal_title:Cell host & microbe

    pub_type: 杂志文章,评审


    authors: Winter SE,Keestra AM,Tsolis RM,Bäumler AJ

    更新日期:2010-07-22 00:00:00

  • A Microbial Drugstore for Motility.

    abstract::While there is growing appreciation that the microbiome regulates gut-brain signaling, the underlying mechanisms remain elusive. In this issue of Cell Host & Microbe, Bhattarai et al. (2018) identify bacteria-derived tryptamine as a ligand for the gut-epithelium-expressed GPCR 5-HT4 receptor, thereby functioning as a ...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Cryan JF,Clarke G,Dinan TG,Schellekens H

    更新日期:2018-06-13 00:00:00

  • Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation.

    abstract::Although Drosophila systemic immunity is extensively studied, little is known about the fly's intestine-specific responses to bacterial infection. Global gene expression analysis of Drosophila intestinal tissue to oral infection with the Gram-negative bacterium Erwinia carotovora revealed that immune responses in the ...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Buchon N,Broderick NA,Poidevin M,Pradervand S,Lemaitre B

    更新日期:2009-02-19 00:00:00

  • The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages.

    abstract::The ecological dynamics underlying the coexistence between antagonistic populations of bacteria and their viruses, bacteriophages (phages), in the mammalian gut microbiota remain poorly understood. We challenged a murine synthetic bacterial community with phages to study the factors allowing phages-bacteria coexistenc...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Lourenço M,Chaffringeon L,Lamy-Besnier Q,Pédron T,Campagne P,Eberl C,Bérard M,Stecher B,Debarbieux L,De Sordi L

    更新日期:2020-09-09 00:00:00

  • Fragment and Conquer.

    abstract::The replication vacuole of Legionella pneumophila makes contact with host mitochondria. In this issue of Cell Host & Microbe, Escoll et al. (2017) dissect the mechanisms of this interaction, the effect of the T4SS effector MitF on mitochondrial function, and the resultant metabolic reprogramming of infected cells to b...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Kozjak-Pavlovic V,Chowdhury SR,Rudel T

    更新日期:2017-09-13 00:00:00

  • Mechanism of adenovirus neutralization by Human alpha-defensins.

    abstract::Defensins are naturally occurring antimicrobial peptides that disrupt bacterial membranes and prevent bacterial invasion of the host. Emerging studies indicate that certain defensins also block virus infection; however, the mechanism(s) involved are poorly understood. We demonstrate that human alpha-defensins inhibit ...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Smith JG,Nemerow GR

    更新日期:2008-01-17 00:00:00

  • HIV-1 Nef assembles a Src family kinase-ZAP-70/Syk-PI3K cascade to downregulate cell-surface MHC-I.

    abstract::HIV-1 Nef, which is required for the efficient onset of AIDS, enhances viral replication and infectivity by exerting multiple effects on infected cells. Nef downregulates cell-surface MHC-I molecules by an uncharacterized PI3K pathway requiring the actions of two Nef motifs-EEEE(65) and PXXP(75). We report that the Ne...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Hung CH,Thomas L,Ruby CE,Atkins KM,Morris NP,Knight ZA,Scholz I,Barklis E,Weinberg AD,Shokat KM,Thomas G

    更新日期:2007-04-19 00:00:00

  • Epigenetics and Genetics of Viral Latency.

    abstract::Viral latency can be considered a metastable, nonproductive infection state that is capable of subsequent reactivation to repeat the infection cycle. Viral latent infections have numerous associated pathologies, including cancer, birth defects, neuropathy, cardiovascular disease, chronic inflammation, and immunologica...

    journal_title:Cell host & microbe

    pub_type: 杂志文章,评审


    authors: Lieberman PM

    更新日期:2016-05-11 00:00:00

  • Phosphoinositides influence pathogen surfing: EPEC rights the SHIP.

    abstract::Tir, a translocated effector protein from enteropathogenic E. coli (EPEC), contains two phosphotyrosines that initiate cellular signaling cascades, leading to localized actin polymerization into pedestals. A recent study now shows that two additional tyrosines within Tir recruit the inositol phosphatase SHIP2 to gener...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Campellone KG

    更新日期:2010-01-21 00:00:00

  • ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.

    abstract::The Cullin-RING E3 ligase (CRL) family is commonly hijacked by pathogens to redirect the host ubiquitin proteasome machinery to specific targets. During HIV infection, CRL5 is hijacked by HIV Vif to target viral restriction factors of the APOBEC3 family for ubiquitination and degradation. Here, using a quantitative pr...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Hüttenhain R,Xu J,Burton LA,Gordon DE,Hultquist JF,Johnson JR,Satkamp L,Hiatt J,Rhee DY,Baek K,Crosby DC,Frankel AD,Marson A,Harper JW,Alpi AF,Schulman BA,Gross JD,Krogan NJ

    更新日期:2019-07-10 00:00:00

  • The relationship of the oral microbiotia to periodontal health and disease.

    abstract::The oral microbial community represents the best-characterized consortium associated with the human host. There are strong correlations between the qualitative composition of the oral microbiota and clinically healthy or diseased states. However, additional studies are needed to elucidate the mechanisms that define th...

    journal_title:Cell host & microbe

    pub_type: 杂志文章,评审


    authors: Curtis MA,Zenobia C,Darveau RP

    更新日期:2011-10-20 00:00:00

  • Intestinal Bile Acids Induce a Morphotype Switch in Vancomycin-Resistant Enterococcus that Facilitates Intestinal Colonization.

    abstract::Vancomycin-resistant Enterococcus (VRE) are highly antibiotic-resistant and readily transmissible pathogens that cause severe infections in hospitalized patients. We discovered that lithocholic acid (LCA), a secondary bile acid prevalent in the cecum and colon of mice and humans, impairs separation of growing VRE dipl...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: McKenney PT,Yan J,Vaubourgeix J,Becattini S,Lampen N,Motzer A,Larson PJ,Dannaoui D,Fujisawa S,Xavier JB,Pamer EG

    更新日期:2019-05-08 00:00:00

  • NMD: nonsense-mediated defense.

    abstract::Initially described as an RNA surveillance pathway, nonsense-mediated decay (NMD) is also recognized to function in the regulation of host gene expression. In this issue of Cell Host & Microbe, three studies describe NMD-mediated defense strategies of plants and mammalian cells in response to pathogen infection. ...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Wachter A,Hartmann L

    更新日期:2014-09-10 00:00:00

  • Anthrax toxin delivers a one-two punch.

    abstract::Although anthrax toxin was identified as a major Bacillus anthracis virulence factor over 50 years ago, defining the physiologically relevant targets has been challenging. Liu et al. demonstrate that intoxication of myeloid-derived cells contributes to establishing infection but is not required for mortality resulting...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Bradley KA,LeVine SM

    更新日期:2010-11-18 00:00:00

  • Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.

    abstract::Our intestinal microbiota harbors a diverse microbial community, often containing opportunistic bacteria with virulence potential. However, mutualistic host-microbial interactions prevent disease by opportunistic pathogens through poorly understood mechanisms. We show that the epithelial interleukin-22 receptor IL-22R...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Pham TA,Clare S,Goulding D,Arasteh JM,Stares MD,Browne HP,Keane JA,Page AJ,Kumasaka N,Kane L,Mottram L,Harcourt K,Hale C,Arends MJ,Gaffney DJ,Sanger Mouse Genetics Project.,Dougan G,Lawley TD

    更新日期:2014-10-08 00:00:00

  • Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria.

    abstract::Thiol-group oxidation of active and allosteric cysteines is a widespread regulatory posttranslational protein modification. Pathogenic bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus, use regulatory cysteine oxidation to respond to and overcome reactive oxygen species (ROS) encountered in the host...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Deng X,Weerapana E,Ulanovskaya O,Sun F,Liang H,Ji Q,Ye Y,Fu Y,Zhou L,Li J,Zhang H,Wang C,Alvarez S,Hicks LM,Lan L,Wu M,Cravatt BF,He C

    更新日期:2013-03-13 00:00:00

  • Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus.

    abstract::Virulence of emerging community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and other highly pathogenic S. aureus strains depends on their production of phenol-soluble modulin (PSM) peptide toxins, which combine the capacities to attract and lyse neutrophils. The molecular basis of PSM-stimulated ...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Kretschmer D,Gleske AK,Rautenberg M,Wang R,Köberle M,Bohn E,Schöneberg T,Rabiet MJ,Boulay F,Klebanoff SJ,van Kessel KA,van Strijp JA,Otto M,Peschel A

    更新日期:2010-06-25 00:00:00

  • Fungal Mimicry of a Mammalian Aminopeptidase Disables Innate Immunity and Promotes Pathogenicity.

    abstract::Systemic fungal infections trigger marked immune-regulatory disturbances, but the mechanisms are poorly understood. We report that the pathogenic yeast of Blastomyces dermatitidis elaborates dipeptidyl-peptidase IVA (DppIVA), a close mimic of the mammalian ectopeptidase CD26, which modulates critical aspects of hemato...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Sterkel AK,Lorenzini JL,Fites JS,Subramanian Vignesh K,Sullivan TD,Wuthrich M,Brandhorst T,Hernandez-Santos N,Deepe GS Jr,Klein BS

    更新日期:2016-03-09 00:00:00

  • Not Your Typical Anti-CRISPR.

    abstract::In this issue of Cell Host & Microbe, two papers by Osuna et al. describe the characterization of AcrIIA1, an anti-CRISPR protein distributed widely among Listeria phages. AcrIIA1 functions as an anti-CRISPR and as a dynamic repressor of acr loci, suggesting it may play an important role in lysogeny. ...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Johnson WE

    更新日期:2020-07-08 00:00:00

  • Host metabolism regulates intracellular growth of Trypanosoma cruzi.

    abstract::Metabolic coupling of intracellular pathogens with host cells is essential for successful colonization of the host. Establishment of intracellular infection by the protozoan Trypanosoma cruzi leads to the development of human Chagas' disease, yet the functional contributions of the host cell toward the infection proce...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Caradonna KL,Engel JC,Jacobi D,Lee CH,Burleigh BA

    更新日期:2013-01-16 00:00:00

  • Adenovirus evasion of interferon-mediated innate immunity by direct antagonism of a cellular histone posttranslational modification.

    abstract::Overcoming the cellular type I interferon (IFN) host defense response is critical for a virus to ensure successful infection. Investigating the effects of human adenovirus (HAdV) infection on global cellular histone posttranslational modification (hPTM), we discovered that virus infection-induced activation of IFN sig...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Fonseca GJ,Thillainadesan G,Yousef AF,Ablack JN,Mossman KL,Torchia J,Mymryk JS

    更新日期:2012-06-14 00:00:00

  • Multi-Donor Longitudinal Antibody Repertoire Sequencing Reveals the Existence of Public Antibody Clonotypes in HIV-1 Infection.

    abstract::Characterization of single antibody lineages within infected individuals has provided insights into the development of Env-specific antibodies. However, a systems-level understanding of the humoral response against HIV-1 is limited. Here, we interrogated the antibody repertoires of multiple HIV-infected donors from an...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Setliff I,McDonnell WJ,Raju N,Bombardi RG,Murji AA,Scheepers C,Ziki R,Mynhardt C,Shepherd BE,Mamchak AA,Garrett N,Karim SA,Mallal SA,Crowe JE Jr,Morris L,Georgiev IS

    更新日期:2018-06-13 00:00:00

  • Structural Analysis of Rabies Virus Glycoprotein Reveals pH-Dependent Conformational Changes and Interactions with a Neutralizing Antibody.

    abstract::Rabies virus (RABV), the etiological agent for the lethal disease of rabies, is a deadly zoonotic pathogen. The RABV glycoprotein (RABV-G) is a key factor mediating virus entry and the major target of neutralizing antibodies. Here, we report the crystal structures of RABV-G solved in the free form at ∼pH-8.0 and in th...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Yang F,Lin S,Ye F,Yang J,Qi J,Chen Z,Lin X,Wang J,Yue D,Cheng Y,Chen Z,Chen H,You Y,Zhang Z,Yang Y,Yang M,Sun H,Li Y,Cao Y,Yang S,Wei Y,Gao GF,Lu G

    更新日期:2020-03-11 00:00:00

  • Bacteria Tell Us How to Protect Our Intestine.

    abstract::The inner colon mucus layer capacity to separate bacteria from the epithelium is dependent on bacterial colonizers signaling to the host epithelium. In this issue of Cell Host & Microbe, Wlodarska et al. (2017) demonstrate that the mucin-utilizing Peptostreptococcus russellii protects the host from inflammatory diseas...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Birchenough G,Hansson GC

    更新日期:2017-07-12 00:00:00

  • Host restriction factor SAMHD1 limits human T cell leukemia virus type 1 infection of monocytes via STING-mediated apoptosis.

    abstract::Human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia and HTLV-1-associated myelopathies. In addition to T cells, HTLV-1 infects cells of the myeloid lineage, which play critical roles in the host innate response to viral infection. Investigating the monocyte depletion observed du...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Sze A,Belgnaoui SM,Olagnier D,Lin R,Hiscott J,van Grevenynghe J

    更新日期:2013-10-16 00:00:00

  • New pieces for the malaria liver stage puzzle: where will they fit?

    abstract::Malaria starts with the infection of the liver by Plasmodium parasites. Although extensive analysis of Plasmodium has revealed the expression patterns of this parasite in every stage of its life cycle, the liver stage remained unexplored. Recently, Tarun et al. have published the first complete transcriptome and prote...

    journal_title:Cell host & microbe

    pub_type: 杂志文章,评审


    authors: Mota MM,Rodriguez A

    更新日期:2008-02-14 00:00:00

  • Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence.

    abstract::Typhoidal and non-typhoidal Salmonelleae (NTS) cause typhoid fever and gastroenteritis, respectively, in humans. Salmonella typhoid toxin contributes to typhoid disease progression and chronic infection, but little is known about the role of its NTS ortholog. We found that typhoid toxin and its NTS ortholog induce dif...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Lee S,Yang YA,Milano SK,Nguyen T,Ahn C,Sim JH,Thompson AJ,Hillpot EC,Yoo G,Paulson JC,Song J

    更新日期:2020-06-10 00:00:00

  • Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection.

    abstract::The transitional epithelium of the bladder normally turns over slowly but upon injury undergoes rapid regeneration fueled by basal uroepithelial stem and/or early progenitor cells (USCs). Little is known about the mechanisms underlying the injury response. We investigate the mechanism of bladder epithelial regeneratio...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Mysorekar IU,Isaacson-Schmid M,Walker JN,Mills JC,Hultgren SJ

    更新日期:2009-05-08 00:00:00

  • KREMEN1 Is a Host Entry Receptor for a Major Group of Enteroviruses.

    abstract::Human type A Enteroviruses (EV-As) cause diseases ranging from hand-foot-and-mouth disease to poliomyelitis-like disease. Although cellular receptors are identified for some EV-As, they remain elusive for the majority of EV-As. We identify the cell surface molecule KREMEN1 as an entry receptor for coxsackievirus A10 (...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Staring J,van den Hengel LG,Raaben M,Blomen VA,Carette JE,Brummelkamp TR

    更新日期:2018-05-09 00:00:00

  • The toxoplasma apicoplast phosphate translocator links cytosolic and apicoplast metabolism and is essential for parasite survival.

    abstract::Apicomplexa are unicellular eukaryotic pathogens that carry a vestigial algal endosymbiont, the apicoplast. The physiological function of the apicoplast and its integration into parasite metabolism remain poorly understood and at times controversial. We establish that the Toxoplasma apicoplast membrane-localized phosp...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Brooks CF,Johnsen H,van Dooren GG,Muthalagi M,Lin SS,Bohne W,Fischer K,Striepen B

    更新日期:2010-01-21 00:00:00