-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Vaginal Challenge with an SIV-Based Dual Reporter System Reveals That Infection Can Occur throughout the Upper and Lower Female Reproductive Tract
There is currently a great effort world-wide to develop interventions such as vaccines and microbicides to decrease, or hopefully block, HIV transmission. To model the infection of women, the field utilizes the rhesus macaque vaginal transmission model. Understanding the initial events leading to infection after viral challenge of the female reproductive tract (FRT) is crucial for the development of functional prevention strategies. To this end, we developed a novel method for detecting infection in the rhesus macaque FRT after vaginal inoculation. This method utilizes single round replication defective vector that expresses dual reporter proteins, Luciferase and mCherry. Monitoring Luciferase expression allows us to identify the sites of infection within the intact FRT, while fluorescent protein mCherry allows us to visualize the single infected cells. Our studies revealed that virus can access the entire upper and lower reproductive tract. Infection occurs primarily in vaginal and ectocervical tissue, but can spread as far as the ovary and local draining lymph nodes. All classically defined susceptible cell types can be infected with the broadly tropic HIV envelope utilized in this study. Prevention strategies aimed at protecting from HIV infection should consider the entire FRT architecture as potentially susceptible and design interventions accordingly.
Vyšlo v časopise: Vaginal Challenge with an SIV-Based Dual Reporter System Reveals That Infection Can Occur throughout the Upper and Lower Female Reproductive Tract. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004440
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004440Souhrn
There is currently a great effort world-wide to develop interventions such as vaccines and microbicides to decrease, or hopefully block, HIV transmission. To model the infection of women, the field utilizes the rhesus macaque vaginal transmission model. Understanding the initial events leading to infection after viral challenge of the female reproductive tract (FRT) is crucial for the development of functional prevention strategies. To this end, we developed a novel method for detecting infection in the rhesus macaque FRT after vaginal inoculation. This method utilizes single round replication defective vector that expresses dual reporter proteins, Luciferase and mCherry. Monitoring Luciferase expression allows us to identify the sites of infection within the intact FRT, while fluorescent protein mCherry allows us to visualize the single infected cells. Our studies revealed that virus can access the entire upper and lower reproductive tract. Infection occurs primarily in vaginal and ectocervical tissue, but can spread as far as the ovary and local draining lymph nodes. All classically defined susceptible cell types can be infected with the broadly tropic HIV envelope utilized in this study. Prevention strategies aimed at protecting from HIV infection should consider the entire FRT architecture as potentially susceptible and design interventions accordingly.
Zdroje
1. Joint United Nations Programme on HIV/AIDS. (2010) Global report: UNAIDS report on the global AIDS epidemic. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS. pp. v.
2. HaynesBF, McElrathMJ (2013) Progress in HIV-1 vaccine development. Curr Opin HIV AIDS 8 : 326–332.
3. ShattockRJ, MooreJP (2003) Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol 1 : 25–34.
4. HaaseAT (2011) Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med 62 : 127–139.
5. KeeleBF, EstesJD (2011) Barriers to mucosal transmission of immunodeficiency viruses. Blood 118 : 839–846.
6. StoneM, KeeleBF, MaZM, BailesE, DutraJ, et al. (2010) A limited number of simian immunodeficiency virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. J Virol 84 : 7083–7095.
7. MillerCJ, LiQ, AbelK, KimEY, MaZM, et al. (2005) Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 79 : 9217–9227.
8. LiQ, EstesJD, SchlievertPM, DuanL, BrosnahanAJ, et al. (2009) Glycerol monolaurate prevents mucosal SIV transmission. Nature 458 : 1034–1038.
9. GrantRM, LamaJR, AndersonPL, McMahanV, LiuAY, et al. (2010) Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. New England Journal of Medicine 363 : 2587–2599.
10. Abdool KarimQ, Abdool KarimSS, FrohlichJA, GroblerAC, BaxterC, et al. (2010) Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329 : 1168–1174.
11. J Marrazzo GR, Nair G, et al.. (2013) Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine or vaginal tenofovir gel in the VOICE study (MTN 003). Conference on Retroviruses and Opportunistic Infections Goergia World Congress Centre, Atlanta.
12. FriendDR, KiserPF (2013) Assessment of topical microbicides to prevent HIV-1 transmission: Concepts, testing, lessons learned. Antiviral Research 99 : 391–400.
13. Van DammeL, CorneliA, AhmedK, AgotK, LombaardJ, et al. (2012) Preexposure Prophylaxis for HIV Infection among African Women. N Engl J Med
14. NegreD, MangeotPE, DuisitG, BlanchardS, VidalainPO, et al. (2000) Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells. Gene Ther 7 : 1613–1623.
15. ShanerNC, CampbellRE, SteinbachPA, GiepmansBN, PalmerAE, et al. (2004) Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22 : 1567–1572.
16. RabinovichBA, YeY, EttoT, ChenJQ, LevitskyHI, et al. (2008) Visualizing fewer than 10 mouse T cells with an enhanced firefly luciferase in immunocompetent mouse models of cancer. Proc Natl Acad Sci U S A 105 : 14342–14346.
17. KoyanagiY, MilesS, MitsuyasuRT, MerrillJE, VintersHV, et al. (1987) Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 236 : 819–822.
18. CroninJ, ZhangXY, ReiserJ (2005) Altering the tropism of lentiviral vectors through pseudotyping. Curr Gene Ther 5 : 387–398.
19. ZuffereyR, DonelloJE, TronoD, HopeTJ (1999) Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Virol 73 : 2886–2892.
20. DonelloJE, LoebJE, HopeTJ (1998) Woodchuck hepatitis virus contains a tripartite posttranscriptional regulatory element. J Virol 72 : 5085–5092.
21. DurandS, CimarelliA (2011) The inside out of lentiviral vectors. Viruses 3 : 132–159.
22. MarxPA, SpiraAI, GettieA, DaileyPJ, VeazeyRS, et al. (1996) Progesterone implants enhance SIV vaginal transmission and early virus load. Nat Med 2 : 1084–1089.
23. LeeB, SharronM, MontanerLJ, WeissmanD, DomsRW (1999) Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci U S A 96 : 5215–5220.
24. PooniaB, WalterL, DufourJ, HarrisonR, MarxPA, et al. (2006) Cyclic changes in the vaginal epithelium of normal rhesus macaques. J Endocrinol 190 : 829–835.
25. MilushJM, KosubD, MarthasM, SchmidtK, ScottF, et al. (2004) Rapid dissemination of SIV following oral inoculation. AIDS 18 : 2371–2380.
26. ZhangZ, SchulerT, ZupancicM, WietgrefeS, StaskusKA, et al. (1999) Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286 : 1353–1357.
27. MillerCJ, ShattockRJ (2003) Target cells in vaginal HIV transmission. Microbes Infect 5 : 59–67.
28. SpiraAI, MarxPA, PattersonBK, MahoneyJ, KoupRA, et al. (1996) Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med 183 : 215–225.
29. HladikF, SakchalathornP, BallweberL, LentzG, FialkowM, et al. (2007) Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 26 : 257–270.
30. PandreaI, ParrishNF, RaehtzK, GaufinT, BarbianHJ, et al. (2012) Mucosal simian immunodeficiency virus transmission in African green monkeys: susceptibility to infection is proportional to target cell availability at mucosal sites. J Virol 86 : 4158–4168.
31. WiraCR, FaheyJV (2008) A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 22 : 1909–1917.
32. CramerDW, WelchWR, BerkowitzRS, GodleskiJJ (2007) Presence of talc in pelvic lymph nodes of a woman with ovarian cancer and long-term genital exposure to cosmetic talc. Obstetrics and gynecology 110 : 498–501.
33. RosenblattKA, WeissNS, Cushing-HaugenKL, WicklundKG, RossingMA (2011) Genital powder exposure and the risk of epithelial ovarian cancer. Cancer Causes Control 22 : 737–742.
34. CookLS, KambML, WeissNS (1997) Perineal powder exposure and the risk of ovarian cancer. Am J Epidemiol 145 : 459–465.
35. BlumenkrantzMJ, GallagherN, BashoreRA, TenckhoffH (1981) Retrograde menstruation in women undergoing chronic peritoneal dialysis. Obstetrics and gynecology 57 : 667–670.
36. HalmeJ, HammondMG, HulkaJF, RajSG, TalbertLM (1984) Retrograde menstruation in healthy women and in patients with endometriosis. Obstetrics and gynecology 64 : 151–154.
37. MasurierC, SalomonB, GuettariN, PiocheC, LachapelleF, et al. (1998) Dendritic cells route human immunodeficiency virus to lymph nodes after vaginal or intravenous administration to mice. J Virol 72 : 7822–7829.
38. GhanemKG, ShahN, KleinRS, MayerKH, SobelJD, et al. (2005) Influence of sex hormones, HIV status, and concomitant sexually transmitted infection on cervicovaginal inflammation. J Infect Dis 191 : 358–366.
39. RotchfordK, StrumAW, WilkinsonD (2000) Effect of coinfection with STDs and of STD treatment on HIV shedding in genital-tract secretions: systematic review and data synthesis. Sex Transm Dis 27 : 243–248.
40. VishwanathanSA, GuenthnerPC, LinCY, DobardC, SharmaS, et al. (2011) High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques. J Acquir Immune Defic Syndr 57 : 261–264.
41. KershEN, HenningT, VishwanathanSA, MorrisM, ButlerK, et al. (2014) SHIV susceptibility changes during the menstrual cycle of pigtail macaques. J Med Primatol [epub ahead of print]..
42. AkiyamaM, OkabeH, TakakuraK, FujiyamaY, NodaY (1999) Expression of macrophage inflammatory protein-1alpha (MIP-1alpha) in human endometrium throughout the menstrual cycle. Br J Obstet Gynaecol 106 : 725–730.
43. KallikourdisM, AndersenKG, WelchKA, BetzAG (2007) Alloantigen-enhanced accumulation of CCR5+ ‘effector’ regulatory T cells in the gravid uterus. Proc Natl Acad Sci U S A 104 : 594–599.
44. PadianNS, van der StratenA, RamjeeG, ChipatoT, de BruynG, et al. (2007) Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial. Lancet 370 : 251–261.
45. WeiX, DeckerJM, LiuH, ZhangZ, AraniRB, et al. (2002) Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 46 : 1896–1905.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Identification of the Microsporidian as a New Target of the IFNγ-Inducible IRG Resistance SystemČlánek Human Cytomegalovirus Drives Epigenetic Imprinting of the Locus in NKG2C Natural Killer CellsČlánek APOBEC3D and APOBEC3F Potently Promote HIV-1 Diversification and Evolution in Humanized Mouse ModelČlánek Role of Non-conventional T Lymphocytes in Respiratory Infections: The Case of the Pneumococcus
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2014 Číslo 10- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
-
Všetky články tohto čísla
- Theory and Empiricism in Virulence Evolution
- -Related Fungi and Reptiles: A Fatal Attraction
- Adaptive Prediction As a Strategy in Microbial Infections
- Antimicrobials, Stress and Mutagenesis
- A Novel Function of Human Pumilio Proteins in Cytoplasmic Sensing of Viral Infection
- Social Motility of African Trypanosomes Is a Property of a Distinct Life-Cycle Stage That Occurs Early in Tsetse Fly Transmission
- Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer
- Identification of the Microsporidian as a New Target of the IFNγ-Inducible IRG Resistance System
- mRNA Structural Constraints on EBNA1 Synthesis Impact on Antigen Presentation and Early Priming of CD8 T Cells
- Infection Causes Distinct Epigenetic DNA Methylation Changes in Host Macrophages
- Neutrophil Crawling in Capillaries; A Novel Immune Response to
- Live Attenuated Vaccine Protects against Pulmonary Challenge in Rats and Non-human Primates
- The ESAT-6 Protein of Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage
- Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus
- HIV Acquisition Is Associated with Increased Antimicrobial Peptides and Reduced HIV Neutralizing IgA in the Foreskin Prepuce of Uncircumcised Men
- Uses a Unique Ligand-Binding Mode for Trapping Opines and Acquiring A Competitive Advantage in the Niche Construction on Plant Host
- Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence
- Ethanol Stimulates WspR-Controlled Biofilm Formation as Part of a Cyclic Relationship Involving Phenazines
- Densovirus Is a Mutualistic Symbiont of a Global Crop Pest () and Protects against a Baculovirus and Bt Biopesticide
- Insights into Intestinal Colonization from Monitoring Fluorescently Labeled Bacteria
- Mycobacterial Antigen Driven Activation of CD14CD16 Monocytes Is a Predictor of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
- Lipoprotein LprG Binds Lipoarabinomannan and Determines Its Cell Envelope Localization to Control Phagolysosomal Fusion
- Dampens the DNA Damage Response
- MicroRNAs Suppress NB Domain Genes in Tomato That Confer Resistance to
- Novel Cyclic di-GMP Effectors of the YajQ Protein Family Control Bacterial Virulence
- Vaginal Challenge with an SIV-Based Dual Reporter System Reveals That Infection Can Occur throughout the Upper and Lower Female Reproductive Tract
- Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks
- One Small Step for a Yeast - Microevolution within Macrophages Renders Hypervirulent Due to a Single Point Mutation
- Expression Profiling during Arabidopsis/Downy Mildew Interaction Reveals a Highly-Expressed Effector That Attenuates Responses to Salicylic Acid
- Human Cytomegalovirus Drives Epigenetic Imprinting of the Locus in NKG2C Natural Killer Cells
- Interaction with Tsg101 Is Necessary for the Efficient Transport and Release of Nucleocapsids in Marburg Virus-Infected Cells
- The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability
- Sterol Biosynthesis Is Required for Heat Resistance but Not Extracellular Survival in
- Allele-Specific Induction of IL-1β Expression by C/EBPβ and PU.1 Contributes to Increased Tuberculosis Susceptibility
- Host Cofactors and Pharmacologic Ligands Share an Essential Interface in HIV-1 Capsid That Is Lost upon Disassembly
- APOBEC3D and APOBEC3F Potently Promote HIV-1 Diversification and Evolution in Humanized Mouse Model
- Structural Basis for the Recognition of Human Cytomegalovirus Glycoprotein B by a Neutralizing Human Antibody
- Systematic Analysis of ZnCys Transcription Factors Required for Development and Pathogenicity by High-Throughput Gene Knockout in the Rice Blast Fungus
- Epstein-Barr Virus Nuclear Antigen 3A Promotes Cellular Proliferation by Repression of the Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1
- The Host Protein Calprotectin Modulates the Type IV Secretion System via Zinc Sequestration
- Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator
- A Novel Alpha Kinase EhAK1 Phosphorylates Actin and Regulates Phagocytosis in
- The pH-Responsive PacC Transcription Factor of Governs Epithelial Entry and Tissue Invasion during Pulmonary Aspergillosis
- Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells
- Co-opted Oxysterol-Binding ORP and VAP Proteins Channel Sterols to RNA Virus Replication Sites via Membrane Contact Sites
- Characteristics of Memory B Cells Elicited by a Highly Efficacious HPV Vaccine in Subjects with No Pre-existing Immunity
- HPV16-E7 Expression in Squamous Epithelium Creates a Local Immune Suppressive Environment via CCL2- and CCL5- Mediated Recruitment of Mast Cells
- Dengue Viruses Are Enhanced by Distinct Populations of Serotype Cross-Reactive Antibodies in Human Immune Sera
- CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells
- A Sialic Acid Binding Site in a Human Picornavirus
- Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus
- Myosins VIII and XI Play Distinct Roles in Reproduction and Transport of
- HTLV-1 Tax Stabilizes MCL-1 via TRAF6-Dependent K63-Linked Polyubiquitination to Promote Cell Survival and Transformation
- Species Complex: Ecology, Phylogeny, Sexual Reproduction, and Virulence
- A Critical Role for IL-17RB Signaling in HTLV-1 Tax-Induced NF-κB Activation and T-Cell Transformation
- Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90
- Role of Non-conventional T Lymphocytes in Respiratory Infections: The Case of the Pneumococcus
- Kaposi's Sarcoma-Associated Herpesvirus Induces Nrf2 during Infection of Endothelial Cells to Create a Microenvironment Conducive to Infection
- A Relay Network of Extracellular Heme-Binding Proteins Drives Iron Acquisition from Hemoglobin
- Glutamate Secretion and Metabotropic Glutamate Receptor 1 Expression during Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Cell Proliferation
- Reduces Malaria and Dengue Infection in Vector Mosquitoes and Has Entomopathogenic and Anti-pathogen Activities
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Novel Cyclic di-GMP Effectors of the YajQ Protein Family Control Bacterial Virulence
- MicroRNAs Suppress NB Domain Genes in Tomato That Confer Resistance to
- The ESAT-6 Protein of Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage
- Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy