-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response
Primary herpes simplex virus (HSV) infections are characterized by acute disease that resolves rapidly, but the virus persists in a latent form in sensory neurons that can be a source of renewed disease. Analyzing gene expression in single mouse neurons harboring latent HSV, we show directly that HSV latency is dynamic and heterogeneous. HSV lytic gene transcripts were frequently detected in latently infected neurons and often in combinations. Expression of selected cellular anti-viral and survival genes showed that transcriptional profiles differed between latently infected and uninfected neurons from the same ganglia. The pattern of host gene expression also differed between latently infected neurons that were and were not experiencing HSV lytic gene expression. Our study suggests that HSV latency is characterized by very frequent switching on of lytic genes and a rapid response by the host, presumably to halt progression to reactivation.
Vyšlo v časopise: Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004237
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004237Souhrn
Primary herpes simplex virus (HSV) infections are characterized by acute disease that resolves rapidly, but the virus persists in a latent form in sensory neurons that can be a source of renewed disease. Analyzing gene expression in single mouse neurons harboring latent HSV, we show directly that HSV latency is dynamic and heterogeneous. HSV lytic gene transcripts were frequently detected in latently infected neurons and often in combinations. Expression of selected cellular anti-viral and survival genes showed that transcriptional profiles differed between latently infected and uninfected neurons from the same ganglia. The pattern of host gene expression also differed between latently infected neurons that were and were not experiencing HSV lytic gene expression. Our study suggests that HSV latency is characterized by very frequent switching on of lytic genes and a rapid response by the host, presumably to halt progression to reactivation.
Zdroje
1. JurakI, SilversteinLB, SharmaM, CoenDM (2012) Herpes Simplex Virus Is Equipped with RNA - and Protein-Based Mechanisms To Repress Expression of ATRX, an Effector of Intrinsic Immunity. J Virol 86 : 10093–10102.
2. WaldA, CoreyL, ConeR, HobsonA, DavisG, et al. (1997) Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment. J Clin Invest 99 : 1092–1097.
3. GebhardtBM, HalfordWP (2005) Evidence that spontaneous reactivation of herpes virus does not occur in mice. Virol J 2 : 67.
4. MesterJC, RouseBT (1991) The mouse model and understanding immunity to herpes simplex virus. Rev Infect Dis 13 Suppl 11: S935–945.
5. DeatlyAM, SpivackJG, LaviE, FraserNW (1987) RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice. Proc Natl Acad Sci U S A 84 : 3204–3208.
6. StevensJG, WagnerEK, Devi-RaoGB, CookML, FeldmanLT (1987) RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 235 : 1056–1059.
7. UmbachJL, KramerMF, JurakI, KarnowskiHW, CoenDM, et al. (2008) MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 454 : 780–783.
8. PengW, HendersonG, InmanM, BenMohamedL, PerngGC, et al. (2005) The locus encompassing the latency-associated transcript of herpes simplex virus type 1 interferes with and delays interferon expression in productively infected neuroblastoma cells and trigeminal Ganglia of acutely infected mice. J Virol 79 : 6162–6171.
9. PerngGC, JonesC, Ciacci-ZanellaJ, StoneM, HendersonG, et al. (2000) Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287 : 1500–1503.
10. ThompsonRL, SawtellNM (2001) Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival. J Virol 75 : 6660–6675.
11. MadorN, GoldenbergD, CohenO, PanetA, SteinerI (1998) Herpes simplex virus type 1 latency-associated transcripts suppress viral replication and reduce immediate-early gene mRNA levels in a neuronal cell line. J Virol 72 : 5067–5075.
12. ChenSH, KramerMF, SchafferPA, CoenDM (1997) A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus. J Virol 71 : 5878–5884.
13. GarberDA, SchafferPA, KnipeDM (1997) A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1. J Virol 71 : 5885–5893.
14. KramerMF, CoenDM (1995) Quantification of transcripts from the ICP4 and thymidine kinase genes in mouse ganglia latently infected with herpes simplex virus. J Virol 69 : 1389–1399.
15. FeldmanLT, EllisonAR, VoytekCC, YangL, KrauseP, et al. (2002) Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. Proc Natl Acad Sci U S A 99 : 978–983.
16. MailletS, NaasT, CrepinS, Roque-AfonsoAM, LafayF, et al. (2006) Herpes simplex virus type 1 latently infected neurons differentially express latency-associated and ICP0 transcripts. J Virol 80 : 9310–9321.
17. GreenMT, CourtneyRJ, DunkelEC (1981) Detection of an immediate early herpes simplex virus type 1 polypeptide in trigeminal ganglia from latently infected animals. Infect Immun 34 : 987–992.
18. ChenSH, LeeLY, GarberDA, SchafferPA, KnipeDM, et al. (2002) Neither LAT nor open reading frame P mutations increase expression of spliced or intron-containing ICP0 transcripts in mouse ganglia latently infected with herpes simplex virus. J Virol 76 : 4764–4772.
19. GiordaniNV, NeumannDM, KwiatkowskiDL, BhattacharjeePS, McAnanyPK, et al. (2008) During herpes simplex virus type 1 infection of rabbits, the ability to express the latency-associated transcript increases latent-phase transcription of lytic genes. J Virol 82 : 6056–6060.
20. KramerMF, ChenSH, KnipeDM, CoenDM (1998) Accumulation of viral transcripts and DNA during establishment of latency by herpes simplex virus. J Virol 72 : 1177–1185.
21. PesolaJM, ZhuJ, KnipeDM, CoenDM (2005) Herpes simplex virus 1 immediate-early and early gene expression during reactivation from latency under conditions that prevent infectious virus production. J Virol 79 : 14516–14525.
22. Tal-SingerR, LasnerTM, PodrzuckiW, SkokotasA, LearyJJ, et al. (1997) Gene expression during reactivation of herpes simplex virus type 1 from latency in the peripheral nervous system is different from that during lytic infection of tissue cultures. J Virol 71 : 5268–5276.
23. DuT, ZhouG, RoizmanB (2011) HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency-associated transcript and miRNAs. Proceedings of the National Academy of Sciences 108 : 18820–18824.
24. PrestonCM (2000) Repression of viral transcription during herpes simplex virus latency. J Gen Virol 81 : 1–19.
25. FritzschFS, DusnyC, FrickO, SchmidA (2012) Single-cell analysis in biotechnology, systems biology, and biocatalysis. Annu Rev Chem Biomol Eng 3 : 129–155.
26. WangD, BodovitzS (2010) Single cell analysis: the new frontier in ‘omics’. Trends Biotechnol 28 : 281–290.
27. GuoG, HussM, TongGQ, WangC, Li SunL, et al. (2010) Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev Cell 18 : 675–685.
28. NarsinhKH, SunN, Sanchez-FreireV, LeeAS, AlmeidaP, et al. (2011) Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells. J Clin Invest 121 : 1217–1221.
29. DalerbaP, KaliskyT, SahooD, RajendranPS, RothenbergME, et al. (2011) Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat Biotechnol 29 : 1120–1127.
30. SawtellNM (1997) Comprehensive quantification of herpes simplex virus latency at the single-cell level. J Virol 71 : 5423–5431.
31. Emmert-BuckMR, BonnerRF, SmithPD, ChuaquiRF, ZhuangZ, et al. (1996) Laser capture microdissection. Science 274 : 998–1001.
32. SimmonsA, NashAA (1984) Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease. J Virol 52 : 816–821.
33. SpivackJG, FraserNW (1987) Detection of herpes simplex virus type 1 transcripts during latent infection in mice. J Virol 61 : 3841–3847.
34. SteinerI, MadorN, ReibsteinI, SpivackJG, FraserNW (1994) Herpes simplex virus type 1 gene expression and reactivation of latent infection in the central nervous system. Neuropathol Appl Neurobiol 20 : 253–260.
35. KrausePR, CroenKD, StrausSE, OstroveJM (1988) Detection and preliminary characterization of herpes simplex virus type 1 transcripts in latently infected human trigeminal ganglia. J Virol 62 : 4819–4823.
36. WagnerEK, BloomDC (1997) Experimental investigation of herpes simplex virus latency. Clin Microbiol Rev 10 : 419–443.
37. KnipeDM, CliffeA (2008) Chromatin control of herpes simplex virus lytic and latent infection. Nat Rev Microbiol 6 : 211–221.
38. RoizmanB, ZhouG, DuT (2011) Checkpoints in productive and latent infections with herpes simplex virus 1: conceptualization of the issues. J Neurovirol 17 : 512–517.
39. ProencaJT, ColemanHM, ConnorV, WintonDJ, EfstathiouS (2008) A historical analysis of herpes simplex virus promoter activation in vivo reveals distinct populations of latently infected neurones. J Gen Virol 89 : 2965–2974.
40. WakimLM, JonesCM, GebhardtT, PrestonCM, CarboneFR (2008) CD8(+) T-cell attenuation of cutaneous herpes simplex virus infection reduces the average viral copy number of the ensuing latent infection. Immunol Cell Biol 86 : 666–675.
41. ChenXP, MataM, KelleyM, GloriosoJC, FinkDJ (2002) The relationship of herpes simplex virus latency associated transcript expression to genome copy number: a quantitative study using laser capture microdissection. J Neurovirol 8 : 204–210.
42. MarmigereF, ErnforsP (2007) Specification and connectivity of neuronal subtypes in the sensory lineage. Nat Rev Neurosci 8 : 114–127.
43. MargolisTP, ImaiY, YangL, VallasV, KrausePR (2007) Herpes simplex virus type 2 (HSV-2) establishes latent infection in a different population of ganglionic neurons than HSV-1: role of latency-associated transcripts. J Virol 81 : 1872–1878.
44. YangL, VoytekCC, MargolisTP (2000) Immunohistochemical analysis of primary sensory neurons latently infected with herpes simplex virus type 1. J Virol 74 : 209–217.
45. MehtaA, MaggioncaldaJ, BagasraO, ThikkavarapuS, SaikumariP, et al. (1995) In situ DNA PCR and RNA hybridization detection of herpes simplex virus sequences in trigeminal ganglia of latently infected mice. Virology 206 : 633–640.
46. MaggioncaldaJ, MehtaA, SuYH, FraserNW, BlockTM (1996) Correlation between herpes simplex virus type 1 rate of reactivation from latent infection and the number of infected neurons in trigeminal ganglia. Virology 225 : 72–81.
47. RamakrishnanR, LevineM, FinkDJ (1994) PCR-based analysis of herpes simplex virus type 1 latency in the rat trigeminal ganglion established with a ribonucleotide reductase-deficient mutant. J Virol 68 : 7083–7091.
48. JurakI, HackenbergM, KimJY, PesolaJM, EverettRD, et al. (2014) Expression of Herpes Simplex Virus 1 MicroRNAs in Cell Culture Models of Quiescent and Latent Infection. J Virol 88 : 2337–2339.
49. JurakI, KramerMF, MellorJC, van LintAL, RothFP, et al. (2010) Numerous Conserved and Divergent MicroRNAs Expressed by Herpes Simplex Viruses 1 and 2. J Virol 84 : 4659–4672.
50. WangQY, ZhouC, JohnsonKE, ColgroveRC, CoenDM, et al. (2005) Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection. Proc Natl Acad Sci U S A 102 : 16055–16059.
51. KhannaKM, BonneauRH, KinchingtonPR, HendricksRL (2003) Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity 18 : 593–603.
52. van LintAL, KleinertL, ClarkeSR, StockA, HeathWR, et al. (2005) Latent infection with herpes simplex virus is associated with ongoing CD8+ T-cell stimulation by parenchymal cells within sensory ganglia. J Virol 79 : 14843–14851.
53. van VelzenM, JingL, OsterhausAD, SetteA, KoelleDM, et al. (2013) Local CD4 and CD8 T-Cell Reactivity to HSV-1 Antigens Documents Broad Viral Protein Expression and Immune Competence in Latently Infected Human Trigeminal Ganglia. PLoS Pathog 9: e1003547.
54. HalfordWP, GebhardtBM, CarrDJ (1996) Persistent cytokine expression in trigeminal ganglion latently infected with herpes simplex virus type 1. J Immunol 157 : 3542–3549.
55. KnickelbeinJE, KhannaKM, YeeMB, BatyCJ, KinchingtonPR, et al. (2008) Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 322 : 268–271.
56. DavisMM, KrogsgaardM, HuseM, HuppaJ, LillemeierBF, et al. (2007) T cells as a self-referential, sensory organ. Annu Rev Immunol 25 : 681–695.
57. MedemaJP, SchuurhuisDH, ReaD, van TongerenJ, de JongJ, et al. (2001) Expression of the serpin serine protease inhibitor 6 protects dendritic cells from cytotoxic T lymphocyte-induced apoptosis: differential modulation by T helper type 1 and type 2 cells. J Exp Med 194 : 657–667.
58. ZhangM, ParkSM, WangY, ShahR, LiuN, et al. (2006) Serine protease inhibitor 6 protects cytotoxic T cells from self-inflicted injury by ensuring the integrity of cytotoxic granules. Immunity 24 : 451–461.
59. KramerMF, JurakI, PesolaJM, BoisselS, KnipeDM, et al. (2011) Herpes simplex virus 1 microRNAs expressed abundantly during latent infection are not essential for latency in mouse trigeminal ganglia. Virology 417 : 239–247.
60. KimJY, MandarinoA, ChaoMV, MohrI, WilsonAC (2012) Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. PLoS Pathog 8: e1002540.
61. TakaokaA, WangZ, ChoiMK, YanaiH, NegishiH, et al. (2007) DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 448 : 501–505.
62. BannardO, KramanM, FearonDT (2009) Secondary replicative function of CD8+ T cells that had developed an effector phenotype. Science 323 : 505–509.
63. van LintA, AyersM, BrooksAG, ColesRM, HeathWR, et al. (2004) Herpes simplex virus-specific CD8+ T cells can clear established lytic infections from skin and nerves and can partially limit the early spread of virus after cutaneous inoculation. J Immunol 172 : 392–397.
64. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 : 402–408.
65. GebhardtT, WhitneyPG, ZaidA, MackayLK, BrooksAG, et al. (2011) Different patterns of peripheral migration by memory CD4+ and CD8+ T cells. Nature 477 : 216–219.
66. McDavidA, FinakG, ChattopadyayPK, DominguezM, LamoreauxL, et al. (2013) Data exploration, quality control and testing in single-cell qPCR-based gene expression experiments. Bioinformatics 29 : 461–467.
67. WarrenL, BryderD, WeissmanIL, QuakeSR (2006) Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR. Proc Natl Acad Sci U S A 103 : 17807–17812.
68. BengtssonM, StahlbergA, RorsmanP, KubistaM (2005) Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels. Genome Res 15 : 1388–1392.
69. RajA, PeskinCS, TranchinaD, VargasDY, TyagiS (2006) Stochastic mRNA synthesis in mammalian cells. PLoS Biol 4: e309.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Molecular and Cellular Mechanisms of KSHV Oncogenesis of Kaposi's Sarcoma Associated with HIV/AIDSČlánek The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV InfectionČlánek Peptidoglycan Recognition Proteins Kill Bacteria by Inducing Oxidative, Thiol, and Metal Stress
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2014 Číslo 7- 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
- Bacteriophages as Vehicles for Antibiotic Resistance Genes in the Environment
- Helminth Infections, Type-2 Immune Response, and Metabolic Syndrome
- Defensins and Viral Infection: Dispelling Common Misconceptions
- Holobiont–Holobiont Interactions: Redefining Host–Parasite Interactions
- The Wide World of Ribosomally Encoded Bacterial Peptides
- Microbial Egress: A Hitchhiker's Guide to Freedom
- Molecular and Cellular Mechanisms of KSHV Oncogenesis of Kaposi's Sarcoma Associated with HIV/AIDS
- HIV-1 Capture and Transmission by Dendritic Cells: The Role of Viral Glycolipids and the Cellular Receptor Siglec-1
- Tetherin Can Restrict Cell-Free and Cell-Cell Transmission of HIV from Primary Macrophages to T Cells
- The Frustrated Host Response to Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines
- Larger Mammalian Body Size Leads to Lower Retroviral Activity
- The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection
- Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response
- Phase Variation of Poly-N-Acetylglucosamine Expression in
- A Screen of Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis
- Structure of the Trehalose-6-phosphate Phosphatase from Reveals Key Design Principles for Anthelmintic Drugs
- The Impact of Juvenile Coxsackievirus Infection on Cardiac Progenitor Cells and Postnatal Heart Development
- Vertical Transmission Selects for Reduced Virulence in a Plant Virus and for Increased Resistance in the Host
- Characterization of the Largest Effector Gene Cluster of
- Novel Drosophila Viruses Encode Host-Specific Suppressors of RNAi
- Pto Kinase Binds Two Domains of AvrPtoB and Its Proximity to the Effector E3 Ligase Determines if It Evades Degradation and Activates Plant Immunity
- Genetic Analysis of Tropism Using a Naturally Attenuated Cutaneous Strain
- Plasmacytoid Dendritic Cells Suppress HIV-1 Replication but Contribute to HIV-1 Induced Immunopathogenesis in Humanized Mice
- A Novel Mouse Model of Gastroenteritis Reveals Key Pro-inflammatory and Tissue Protective Roles for Toll-like Receptor Signaling during Infection
- Pathogenicity of Is Expressed by Regulating Metabolic Thresholds of the Host Macrophage
- BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of and
- Independent Bottlenecks Characterize Colonization of Systemic Compartments and Gut Lymphoid Tissue by
- Peptidoglycan Recognition Proteins Kill Bacteria by Inducing Oxidative, Thiol, and Metal Stress
- G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA
- Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry
- The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Effector Proteins
- Arabidopsis LIP5, a Positive Regulator of Multivesicular Body Biogenesis, Is a Critical Target of Pathogen-Responsive MAPK Cascade in Plant Basal Defense
- Plant Surface Cues Prime for Biotrophic Development
- Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis
- The CD27L and CTP1L Endolysins Targeting Contain a Built-in Trigger and Release Factor
- cGMP and NHR Signaling Co-regulate Expression of Insulin-Like Peptides and Developmental Activation of Infective Larvae in
- Systemic Hematogenous Maintenance of Memory Inflation by MCMV Infection
- Strain-Specific Variation of the Decorin-Binding Adhesin DbpA Influences the Tissue Tropism of the Lyme Disease Spirochete
- Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation
- Serovar Typhi Conceals the Invasion-Associated Type Three Secretion System from the Innate Immune System by Gene Regulation
- LANA Binds to Multiple Active Viral and Cellular Promoters and Associates with the H3K4Methyltransferase hSET1 Complex
- A Molecularly Cloned, Live-Attenuated Japanese Encephalitis Vaccine SA-14-2 Virus: A Conserved Single Amino Acid in the Hairpin of the Viral E Glycoprotein Determines Neurovirulence in Mice
- Illuminating Fungal Infections with Bioluminescence
- Comparative Genomics of Plant Fungal Pathogens: The - Paradigm
- Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by
- Widespread Sequence Variations in VAMP1 across Vertebrates Suggest a Potential Selective Pressure from Botulinum Neurotoxins
- An Immunity-Triggering Effector from the Barley Smut Fungus Resides in an Ustilaginaceae-Specific Cluster Bearing Signs of Transposable Element-Assisted Evolution
- Establishment of Murine Gammaherpesvirus Latency in B Cells Is Not a Stochastic Event
- Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis
- Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection
- Innate Immune Responses and Rapid Control of Inflammation in African Green Monkeys Treated or Not with Interferon-Alpha during Primary SIVagm Infection
- Chitin-Degrading Protein CBP49 Is a Key Virulence Factor in American Foulbrood of Honey Bees
- Influenza A Virus Host Shutoff Disables Antiviral Stress-Induced Translation Arrest
- Nsp9 and Nsp10 Contribute to the Fatal Virulence of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Emerging in China
- Pulmonary Infection with Hypervirulent Mycobacteria Reveals a Crucial Role for the P2X7 Receptor in Aggressive Forms of Tuberculosis
- Syk Signaling in Dendritic Cells Orchestrates Innate Resistance to Systemic Fungal Infection
- A Repetitive DNA Element Regulates Expression of the Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
- T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+ T Cells in HIV Infection
- Israeli Acute Paralysis Virus: Epidemiology, Pathogenesis and Implications for Honey Bee Health
- Influence of ND10 Components on Epigenetic Determinants of Early KSHV Latency Establishment
- Antibody to gp41 MPER Alters Functional Properties of HIV-1 Env without Complete Neutralization
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Molecular and Cellular Mechanisms of KSHV Oncogenesis of Kaposi's Sarcoma Associated with HIV/AIDS
- Holobiont–Holobiont Interactions: Redefining Host–Parasite Interactions
- BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of and
- Helminth Infections, Type-2 Immune Response, and Metabolic Syndrome
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