Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1.

Abstract:

:Host genetic variation modifying HIV-1 acquisition risk can inform development of HIV-1 prevention strategies. However, associations between rare or intermediate-frequency variants and HIV-1 acquisition are not well studied. We tested for the association between variation in genic regions and extreme HIV-1 acquisition phenotypes in 100 sub-Saharan Africans with whole genome sequencing data. Missense variants in immunoglobulin-like regions of CD101 and, among women, one missense/5' UTR variant in UBE2V1, were associated with increased HIV-1 acquisition risk (p = 1.9x10-4 and p = 3.7x10-3, respectively, for replication). Both of these genes are known to impact host inflammatory pathways. Effect sizes increased with exposure to HIV-1 after adjusting for the independent effect of increasing exposure on acquisition risk. TRIAL REGISTRATION:ClinicalTrials.gov NCT00194519; NCT00557245.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Mackelprang RD,Bamshad MJ,Chong JX,Hou X,Buckingham KJ,Shively K,deBruyn G,Mugo NR,Mullins JI,McElrath MJ,Baeten JM,Celum C,Emond MJ,Lingappa JR,Partners in Prevention HSV\/HIV Transmission Study and the Partners PrEP Study T

doi

10.1371/journal.ppat.1006703

subject

Has Abstract

pub_date

2017-11-06 00:00:00

pages

e1006703

issue

11

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-17-00261

journal_volume

13

pub_type

杂志文章
  • Nuclear hormone receptor regulation of microRNAs controls innate immune responses in C. elegans.

    abstract::Nuclear hormone receptors respond to small molecules such as retinoids or steroids and regulate development. Signaling in the conserved p38/PMK-1 MAP kinase pathway regulates innate immunity. In this study, we show that the Caenorhabditis elegans nuclear receptor DAF-12 negatively regulates the defense against pathoge...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003545

    authors: Liu F,He CX,Luo LJ,Zou QL,Zhao YX,Saini R,Han SF,Knölker HJ,Wang LS,Ge BX

    更新日期:2013-01-01 00:00:00

  • Cryptosporidium Lactate Dehydrogenase Is Associated with the Parasitophorous Vacuole Membrane and Is a Potential Target for Developing Therapeutics.

    abstract::The apicomplexan, Cryptosporidium parvum, possesses a bacterial-type lactate dehydrogenase (CpLDH). This is considered to be an essential enzyme, as this parasite lacks the Krebs cycle and cytochrome-based respiration, and mainly-if not solely, relies on glycolysis to produce ATP. Here, we provide evidence that in ext...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005250

    authors: Zhang H,Guo F,Zhu G

    更新日期:2015-11-12 00:00:00

  • Bidirectional introgressive hybridization between a cattle and human schistosome species.

    abstract::Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions, caused by parasitic flatworms of the genus Schistosoma (subclass Digenea). Following major water development schemes in the 1980s, schistosomiasis has become an important parasitic disease of children living in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000571

    authors: Huyse T,Webster BL,Geldof S,Stothard JR,Diaw OT,Polman K,Rollinson D

    更新日期:2009-09-01 00:00:00

  • Sub-inhibitory concentrations of human α-defensin potentiate neutralizing antibodies against HIV-1 gp41 pre-hairpin intermediates in the presence of serum.

    abstract::Human defensins are at the forefront of the host responses to HIV and other pathogens in mucosal tissues. However, their ability to inactivate HIV in the bloodstream has been questioned due to the antagonistic effect of serum. In this study, we have examined the effect of sub-inhibitory concentrations of human α-defen...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003431

    authors: Demirkhanyan L,Marin M,Lu W,Melikyan GB

    更新日期:2013-01-01 00:00:00

  • Disruption of Specific RNA-RNA Interactions in a Double-Stranded RNA Virus Inhibits Genome Packaging and Virus Infectivity.

    abstract::Bluetongue virus (BTV) causes hemorrhagic disease in economically important livestock. The BTV genome is organized into ten discrete double-stranded RNA molecules (S1-S10) which have been suggested to follow a sequential packaging pathway from smallest to largest segment during virus capsid assembly. To substantiate a...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005321

    authors: Fajardo T Jr,Sung PY,Roy P

    更新日期:2015-12-08 00:00:00

  • Forward genetic screening identifies a small molecule that blocks Toxoplasma gondii growth by inhibiting both host- and parasite-encoded kinases.

    abstract::The simultaneous targeting of host and pathogen processes represents an untapped approach for the treatment of intracellular infections. Hypoxia-inducible factor-1 (HIF-1) is a host cell transcription factor that is activated by and required for the growth of the intracellular protozoan parasite Toxoplasma gondii at p...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004180

    authors: Brown KM,Suvorova E,Farrell A,McLain A,Dittmar A,Wiley GB,Marth G,Gaffney PM,Gubbels MJ,White M,Blader IJ

    更新日期:2014-06-12 00:00:00

  • Separate domains of G3BP promote efficient clustering of alphavirus replication complexes and recruitment of the translation initiation machinery.

    abstract::G3BP-1 and -2 (hereafter referred to as G3BP) are multifunctional RNA-binding proteins involved in stress granule (SG) assembly. Viruses from diverse families target G3BP for recruitment to replication or transcription complexes in order to block SG assembly but also to acquire pro-viral effects via other unknown func...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007842

    authors: Götte B,Panas MD,Hellström K,Liu L,Samreen B,Larsson O,Ahola T,McInerney GM

    更新日期:2019-06-14 00:00:00

  • CD103+ Conventional Dendritic Cells Are Critical for TLR7/9-Dependent Host Defense against Histoplasma capsulatum, an Endemic Fungal Pathogen of Humans.

    abstract::Innate immune cells shape the host response to microbial pathogens. Here we elucidate critical differences in the molecular response of macrophages vs. dendritic cells (DCs) to Histoplasma capsulatum, an intracellular fungal pathogen of humans. It has long been known that macrophages are permissive for Histoplasma gro...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005749

    authors: Van Prooyen N,Henderson CA,Hocking Murray D,Sil A

    更新日期:2016-07-26 00:00:00

  • Lectin-like bacteriocins from Pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor.

    abstract::Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003898

    authors: McCaughey LC,Grinter R,Josts I,Roszak AW,Waløen KI,Cogdell RJ,Milner J,Evans T,Kelly S,Tucker NP,Byron O,Smith B,Walker D

    更新日期:2014-02-06 00:00:00

  • Host defense and recruitment of Foxp3⁺ T regulatory cells to the lungs in chronic Mycobacterium tuberculosis infection requires toll-like receptor 2.

    abstract::Acute resistance to low dose M. tuberculosis (Mtb) infection is not dependent on Toll-like receptor (TLR) 2. However, whether TLR2 contributes to resistance in chronic Mtb infection has remained uncertain. Here we report that, following low dose aerosol infection with Mtb, mice lacking TLR2 (TLR2KO), in comparison wit...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003397

    authors: McBride A,Konowich J,Salgame P

    更新日期:2013-01-01 00:00:00

  • Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N.

    abstract::Since 2003, more than 380 cases of H5N1 influenza virus infection of humans have been reported. Although the resultant disease in these cases was often severe or fatal, transmission of avian influenza viruses between humans is rare. The precise nature of the barrier blocking human-to-human spread is unknown. It is cle...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000252

    authors: Steel J,Lowen AC,Mubareka S,Palese P

    更新日期:2009-01-01 00:00:00

  • Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems.

    abstract::The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates--effector proteins--are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000375

    authors: Samudrala R,Heffron F,McDermott JE

    更新日期:2009-04-01 00:00:00

  • KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma.

    abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) vGPCR is a constitutively active G protein-coupled receptor that subverts proliferative and inflammatory signaling pathways to induce cell transformation in Kaposi's sarcoma. Cyclooxygenase-2 (COX-2) is an inflammatory mediator that plays a key regulatory role in the acti...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009006

    authors: Medina MV,D Agostino A,Ma Q,Eroles P,Cavallin L,Chiozzini C,Sapochnik D,Cymeryng C,Hyjek E,Cesarman E,Naipauer J,Mesri EA,Coso OA

    更新日期:2020-10-15 00:00:00

  • HIV capsid is a tractable target for small molecule therapeutic intervention.

    abstract::Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that di...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001220

    authors: Blair WS,Pickford C,Irving SL,Brown DG,Anderson M,Bazin R,Cao J,Ciaramella G,Isaacson J,Jackson L,Hunt R,Kjerrstrom A,Nieman JA,Patick AK,Perros M,Scott AD,Whitby K,Wu H,Butler SL

    更新日期:2010-12-09 00:00:00

  • Non-human primate model of Kaposi's sarcoma-associated herpesvirus infection.

    abstract::Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) was first identified in Kaposi's sarcoma (KS) lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000606

    authors: Chang H,Wachtman LM,Pearson CB,Lee JS,Lee HR,Lee SH,Vieira J,Mansfield KG,Jung JU

    更新日期:2009-10-01 00:00:00

  • Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.

    abstract::The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic p...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000346

    authors: Holden MT,Heather Z,Paillot R,Steward KF,Webb K,Ainslie F,Jourdan T,Bason NC,Holroyd NE,Mungall K,Quail MA,Sanders M,Simmonds M,Willey D,Brooks K,Aanensen DM,Spratt BG,Jolley KA,Maiden MC,Kehoe M,Chanter N,Bentl

    更新日期:2009-03-01 00:00:00

  • Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication.

    abstract::Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during infl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006635

    authors: Kuss-Duerkop SK,Wang J,Mena I,White K,Metreveli G,Sakthivel R,Mata MA,Muñoz-Moreno R,Chen X,Krammer F,Diamond MS,Chen ZJ,García-Sastre A,Fontoura BMA

    更新日期:2017-09-27 00:00:00

  • Multiple roles of core protein linker in hepatitis B virus replication.

    abstract::Hepatitis B virus (HBV) core protein (HBc) contains an N-terminal domain (NTD, assembly domain) and a C-terminal domain (CTD), which are linked by a flexible linker region. HBc plays multiple essential roles in viral replication, including capsid assembly, packaging of the viral pregenomic RNA (pgRNA) into nucleocapsi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007085

    authors: Liu K,Luckenbaugh L,Ning X,Xi J,Hu J

    更新日期:2018-05-21 00:00:00

  • EBNA2-deleted Epstein-Barr virus (EBV) isolate, P3HR1, causes Hodgkin-like lymphomas and diffuse large B cell lymphomas with type II and Wp-restricted latency types in humanized mice.

    abstract::EBV transforms B cells in vitro and causes human B-cell lymphomas including classical Hodgkin lymphoma (CHL), Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). The EBV latency protein, EBNA2, transcriptionally activates the promoters of all latent viral protein-coding genes expressed in type III EBV lat...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008590

    authors: Li C,Romero-Masters JC,Huebner S,Ohashi M,Hayes M,Bristol JA,Nelson SE,Eichelberg MR,Van Sciver N,Ranheim EA,Scott RS,Johannsen EC,Kenney SC

    更新日期:2020-06-15 00:00:00

  • A Novel extracytoplasmic function (ECF) sigma factor regulates virulence in Pseudomonas aeruginosa.

    abstract::Next to the two-component and quorum sensing systems, cell-surface signaling (CSS) has been recently identified as an important regulatory system in Pseudomonas aeruginosa. CSS systems sense signals from outside the cell and transmit them into the cytoplasm. They generally consist of a TonB-dependent outer membrane re...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000572

    authors: Llamas MA,van der Sar A,Chu BC,Sparrius M,Vogel HJ,Bitter W

    更新日期:2009-09-01 00:00:00

  • Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces.

    abstract::Interactions of influenza A virus (IAV) with sialic acid (SIA) receptors determine viral fitness and host tropism. Binding to mucus decoy receptors and receptors on epithelial host cells is determined by a receptor-binding hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in vivo receptor-repe...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007233

    authors: Guo H,Rabouw H,Slomp A,Dai M,van der Vegt F,van Lent JWM,McBride R,Paulson JC,de Groot RJ,van Kuppeveld FJM,de Vries E,de Haan CAM

    更新日期:2018-08-13 00:00:00

  • C. elegans germ cells show temperature and age-dependent expression of Cer1, a Gypsy/Ty3-related retrotransposon.

    abstract::Virus-like particles (VLPs) have not been observed in Caenorhabditis germ cells, although nematode genomes contain low numbers of retrotransposon and retroviral sequences. We used electron microscopy to search for VLPs in various wild strains of Caenorhabditis, and observed very rare candidate VLPs in some strains, in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002591

    authors: Dennis S,Sheth U,Feldman JL,English KA,Priess JR

    更新日期:2012-01-01 00:00:00

  • Serum-dependent selective expression of EhTMKB1-9, a member of Entamoeba histolytica B1 family of transmembrane kinases.

    abstract::Entamoeba histolytica transmembrane kinases (EhTMKs) can be grouped into six distinct families on the basis of motifs and sequences. Analysis of the E. histolytica genome revealed the presence of 35 EhTMKB1 members on the basis of sequence identity (>or=95%). Only six homologs were full length containing an extracellu...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000929

    authors: Shrimal S,Bhattacharya S,Bhattacharya A

    更新日期:2010-06-03 00:00:00

  • A compact viral processing proteinase/ubiquitin hydrolase from the OTU family.

    abstract::Turnip yellow mosaic virus (TYMV)--a member of the alphavirus-like supergroup of viruses--serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (P...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003560

    authors: Lombardi C,Ayach M,Beaurepaire L,Chenon M,Andreani J,Guerois R,Jupin I,Bressanelli S

    更新日期:2013-08-01 00:00:00

  • Systematic Structural Analyses of Attachment Organelle in Mycoplasma pneumoniae.

    abstract::Mycoplasma pneumoniae, a human pathogenic bacterium, glides on host cell surfaces by a unique and unknown mechanism. It forms an attachment organelle at a cell pole as a membrane protrusion composed of surface and internal structures, with a highly organized architecture. In the present study, we succeeded in isolatin...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005299

    authors: Nakane D,Kenri T,Matsuo L,Miyata M

    更新日期:2015-12-03 00:00:00

  • Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli.

    abstract::Toxin-antitoxin (TA) systems are prevalent in many bacterial genomes and have been implicated in biofilm and persister cell formation, but the contribution of individual chromosomally encoded TA systems during bacterial pathogenesis is not well understood. Of the known TA systems encoded by Escherichia coli, only a su...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002954

    authors: Norton JP,Mulvey MA

    更新日期:2012-01-01 00:00:00

  • Parallel epigenomic and transcriptomic responses to viral infection in honey bees (Apis mellifera).

    abstract::Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity i...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004713

    authors: Galbraith DA,Yang X,Niño EL,Yi S,Grozinger C

    更新日期:2015-03-26 00:00:00

  • Vibrio cholerae infection of Drosophila melanogaster mimics the human disease cholera.

    abstract::Cholera, the pandemic diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, continues to be a major public health challenge in the developing world. Cholera toxin, which is responsible for the voluminous stools of cholera, causes constitutive activation of adenylyl cyclase, resulting in the export o...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0010008

    authors: Blow NS,Salomon RN,Garrity K,Reveillaud I,Kopin A,Jackson FR,Watnick PI

    更新日期:2005-09-01 00:00:00

  • Yes, research matters.

    abstract::My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006420

    authors: Shinohara ML

    更新日期:2017-08-10 00:00:00

  • H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

    abstract::A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006276

    authors: Russier M,Yang G,Marinova-Petkova A,Vogel P,Kaplan BS,Webby RJ,Russell CJ

    更新日期:2017-03-10 00:00:00