-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
High Heritability Is Compatible with the Broad Distribution of Set Point Viral Load in HIV Carriers
Following an initial peak in viremia, the viral load in HIV infected patients settles down to a set point which remains more or less stable during chronic HIV infection. This set point viral load is one of the key factors determining the rate of disease progression. The extent to which it is determined by the virus versus host genetics is thus central to developing a better understanding of disease progression. Here we develop an analytical model that describes the changes of the distribution of set point viral load in the HIV carrier population over a full cycle of transmission. Applying this model to patient data we find that the most parsimonious explanation for the observed large variation of set point viral load across HIV patients is that set point viral load is highly heritable from donors to recipients. This implies that set point viral load is to a considerable extent under the genetic control of the virus.
Vyšlo v časopise: High Heritability Is Compatible with the Broad Distribution of Set Point Viral Load in HIV Carriers. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004634
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004634Souhrn
Following an initial peak in viremia, the viral load in HIV infected patients settles down to a set point which remains more or less stable during chronic HIV infection. This set point viral load is one of the key factors determining the rate of disease progression. The extent to which it is determined by the virus versus host genetics is thus central to developing a better understanding of disease progression. Here we develop an analytical model that describes the changes of the distribution of set point viral load in the HIV carrier population over a full cycle of transmission. Applying this model to patient data we find that the most parsimonious explanation for the observed large variation of set point viral load across HIV patients is that set point viral load is highly heritable from donors to recipients. This implies that set point viral load is to a considerable extent under the genetic control of the virus.
Zdroje
1. O’Brien TR, Rosenberg PS, Yellin F, Goedert JJ (1998) Longitudinal HIV-1 RNA levels in a cohort of homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol 18 : 155–61. doi: 10.1097/00042560-199806010-00007 9637580
2. Sabin CA, Devereux H, Phillips AN, Hill A, Janossy G, et al. (2000) Course of viral load throughout HIV-1 infection. J Acquir Immune Defic Syndr 23 : 172–7. doi: 10.1097/00042560-200002010-00009 10737432
3. Mellors JW, Rinaldo CR Jr, Gupta P, White RM, Todd JA, et al. (1996) Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272 : 1167–70. doi: 10.1126/science.272.5265.1167 8638160
4. Bonhoeffer S, Funk GA, Günthard HF, Fischer M, Müller V (2003) Glancing behind virus load variation in HIV-1 infection. Trends Microbiol 11 : 499–504. doi: 10.1016/j.tim.2003.09.002 14607066
5. Geskus RB, Prins M, Hubert JB, Miedema F, Berkhout B, et al. (2007) The HIV RNA setpoint theory revisited. Retrovirology 4 : 65. doi: 10.1186/1742-4690-4-65 17888148
6. Fraser C, Hollingsworth TD, Chapman R, de Wolf F, Hanage WP (2007) Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci U S A 104 : 17441–6. doi: 10.1073/pnas.0708559104 17954909
7. Meyer L, Magierowska M, Hubert JB, Rouzioux C, Deveau C, et al. (1997) Early protective effect of CCR-5 delta 32 heterozygosity on HIV-1 disease progression: relationship with viral load. The SEROCO Study Group. AIDS 11: F73–8. doi: 10.1097/00002030-199711000-00001 9302436
8. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, et al. (2007) A whole-genome association study of major determinants for host control of HIV-1. Science 317 : 944–7. doi: 10.1126/science.1143767 17641165
9. Fellay J, Ge D, Shianna KV, Colombo S, Ledergerber B, et al. (2009) Common genetic variation and the control of HIV-1 in humans. PLoS Genet 5: e1000791. doi: 10.1371/journal.pgen.1000791 20041166
10. Dalmasso C, Carpentier W, Meyer L, Rouzioux C, Goujard C, et al. (2008) Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study. PLoS One 3: e3907. doi: 10.1371/journal.pone.0003907 19107206
11. Limou S, Le Clerc S, Coulonges C, Carpentier W, Dina C, et al. (2009) Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). J Infect Dis 199 : 419–26. doi: 10.1086/596067 19115949
12. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461 : 747–53. doi: 10.1038/nature08494 19812666
13. Learmont JC, Geczy AF, Mills J, Ashton LJ, Raynes-Greenow CH, et al. (1999) Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort. N Engl J Med 340 : 1715–22. doi: 10.1056/NEJM199906033402203 10352163
14. Kouyos RD, von Wyl V, Hinkley T, Petropoulos CJ, Haddad M, et al. (2011) Assessing predicted HIV-1 replicative capacity in a clinical setting. PLoS Pathog 7: e1002321. doi: 10.1371/journal.ppat.1002321 22072960
15. Quiñones-Mateu ME, Ball SC, Marozsan AJ, Torre VS, Albright JL, et al. (2000) A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression. J Virol 74 : 9222–33. doi: 10.1128/JVI.74.19.9222-9233.2000 10982369
16. Barbour JD, Hecht FM, Wrin T, Segal MR, Ramstead CA, et al. (2004) Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection. J Infect Dis 190 : 251–6. doi: 10.1086/422036 15216458
17. Tang J, Tang S, Lobashevsky E, Zulu I, Aldrovandi G, et al. (2004) HLA allele sharing and HIV type 1 viremia in seroconverting Zambians with known transmitting partners. AIDS Res Hum Retroviruses 20 : 19–25. doi: 10.1089/088922204322749468 15000695
18. Hecht FM, Hartogensis W, Bragg L, Bacchetti P, Atchison R, et al. (2010) HIV RNA level in early infection is predicted by viral load in the transmission source. AIDS 24 : 941–5. doi: 10.1097/QAD.0b013e328337b12e 20168202
19. Hollingsworth TD, Laeyendecker O, Shirreff G, Donnelly CA, Serwadda D, et al. (2010) HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda. PLoS Pathog 6: e1000876. doi: 10.1371/journal.ppat.1000876 20463808
20. van der Kuyl AC, Jurriaans S, Pollakis G, Bakker M, Cornelissen M (2010) HIV RNA levels in transmission sources only weakly predict plasma viral load in recipients. AIDS 24 : 1607–8. doi: 10.1097/QAD.0b013e32833b318f 20539098
21. Alizon S, von Wyl V, Stadler T, Kouyos RD, Yerly S, et al. (2010) Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load. PLoS Pathog 6: e1001123. doi: 10.1371/journal.ppat.1001123 20941398
22. Hodcroft E, Hadfield JD, Fearnhill E, Phillips A, Dunn D, et al. (2014) The contribution of viral genotype to plasma viral set-point in HIV infection. PLoS Pathog 10: e1004112. doi: 10.1371/journal.ppat.1004112 24789308
23. Müller V, Fraser C, Herbeck JT (2011) A strong case for viral genetic factors in HIV virulence. Viruses 3 : 204–16. doi: 10.3390/v3030204 21994727
24. Fraser C, Lythgoe K, Leventhal GE, Shirreff G, Hollingsworth TD, et al. (2014) Virulence and pathogenesis of HIV-1 infection: an evolutionary perspective. Science 343 : 1243727. doi: 10.1126/science.1243727 24653038
25. Shirreff G, Pellis L, Laeyendecker O, Fraser C (2011) Transmission selects for HIV-1 strains of intermediate virulence: a modelling approach. PLoS Comput Biol 7: e1002185. doi: 10.1371/journal.pcbi.1002185 22022243
26. Easterling MR, Ellner SP, Dixon PM (2000) Size-specific sensitivity: Applying a new structured population model. Ecology 81 : 694–708. doi: 10.1890/0012-9658(2000)081%5B0694:SSSAAN%5D2.0.CO;2
27. Ellner SP, Rees M (2006) Integral Projection Models for Species with Complex Demography. Am Nat 167 : 410–428. doi: 10.1086/499438 16673349
28. Coulson T (2012) Integral projections models, their construction and use in posing hypotheses in ecology. Oikos 121 : 1337–1350. doi: 10.1111/j.1600-0706.2012.00035.x
29. Carlson JM, Schaefer M, Monaco DC, Batorsky R, Claiborne DT, et al. (2014) HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science 345 : 1254031. doi: 10.1126/science.1254031 25013080
30. Lythgoe KA, Pellis L, Fraser C (2013) Is HIV short-sighted? Insights from a multistrain nested model. Evolution 67 : 2769–82. doi: 10.1111/evo.12166 24094332
31. Herbeck JT, Müller V, Maust BS, Ledergerber B, Torti C, et al. (2012) Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission. AIDS 26 : 193–205. doi: 10.1097/QAD.0b013e32834db418 22089381
32. Williams BG (2011) Determinants of sexual transmission of HV: implications for control. arXiv:11084715.
33. Shankarappa R, Margolick JB, Gange SJ, Rodrigo AG, Upchurch D, et al. (1999) Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol 73 : 10489–502. 10559367
34. Bartha I, Simon P, Müller V (2008) Has HIV evolved to induce immune pathogenesis? Trends Immunol 29 : 322–8. doi: 10.1016/j.it.2008.04.005 18524680
35. Hool A, Leventhal GE, Bonhoeffer S (2013) Virus-induced target cell activation reconciles set-point viral load heritability and within-host evolution. Epidemics 5 : 174–80. doi: 10.1016/j.epidem.2013.09.002 24267873
36. Childs DZ, Rees M, Rose KE, Grubb PJ, Ellner SP (2004) Evolution of size-dependent flowering in a variable environment: construction and analysis of a stochastic integral projection model. Proc Biol Sci 271 : 425–34. doi: 10.1098/rspb.2003.2597 15101702
37. Coulson T, MacNulty DR, Stahler DR, vonHoldt B, Wayne RK, et al. (2011) Modeling effects of environmental change on wolf population dynamics, trait evolution, and life history. Science 334 : 1275–8. doi: 10.1126/science.1209441 22144626
38. Bartha I, Carlson JM, Brumme CJ, McLaren PJ, Brumme ZL, et al. (2013) A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. Elife 2: e01123. doi: 10.7554/eLife.01123 24171102
39. Falconer DS (1981) Introduction to quantitative genetics. Longman (New York), 2nd edition.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2015 Číslo 2- 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
- 2014 Reviewer Thank You
- A Case for Two-Component Signaling Systems As Antifungal Drug Targets
- Prions—Not Your Immunologist’s Pathogen
- Telomeric ORFS in : Does Mediator Tail Wag the Yeast?
- Livestock-Associated : The United States Experience
- The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Infection
- The Intracellular Bacterium Uses Parasitoid Wasps as Phoretic Vectors for Efficient Horizontal Transmission
- CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue
- Phage-mediated Dispersal of Biofilm and Distribution of Bacterial Virulence Genes Is Induced by Quorum Sensing
- CXCL9 Contributes to Antimicrobial Protection of the Gut during Infection Independent of Chemokine-Receptor Signaling
- Mitigation of Prion Infectivity and Conversion Capacity by a Simulated Natural Process—Repeated Cycles of Drying and Wetting
- Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria
- Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Invasion of Erythrocytes
- Crystal Structures of the Carboxyl cGMP Binding Domain of the cGMP-dependent Protein Kinase Reveal a Novel Capping Triad Crucial for Merozoite Egress
- Non-redundant and Redundant Roles of Cytomegalovirus gH/gL Complexes in Host Organ Entry and Intra-tissue Spread
- Characterization of Metabolically Quiescent Parasites in Murine Lesions Using Heavy Water Labeling
- A Working Model of How Noroviruses Infect the Intestine
- CD44 Plays a Functional Role in -induced Epithelial Cell Proliferation
- Novel Inhibitors of Cholesterol Degradation in Reveal How the Bacterium’s Metabolism Is Constrained by the Intracellular Environment
- G-Quadruplexes in Pathogens: A Common Route to Virulence Control?
- A Rho GDP Dissociation Inhibitor Produced by Apoptotic T-Cells Inhibits Growth of
- Manipulating Adenovirus Hexon Hypervariable Loops Dictates Immune Neutralisation and Coagulation Factor X-dependent Cell Interaction and
- The RhoGAP SPIN6 Associates with SPL11 and OsRac1 and Negatively Regulates Programmed Cell Death and Innate Immunity in Rice
- Lymph-Node Resident CD8α Dendritic Cells Capture Antigens from Migratory Malaria Sporozoites and Induce CD8 T Cell Responses
- Coordinated Function of Cellular DEAD-Box Helicases in Suppression of Viral RNA Recombination and Maintenance of Viral Genome Integrity
- IL-33-Mediated Protection against Experimental Cerebral Malaria Is Linked to Induction of Type 2 Innate Lymphoid Cells, M2 Macrophages and Regulatory T Cells
- Evasion of Autophagy and Intracellular Killing by Human Myeloid Dendritic Cells Involves DC-SIGN-TLR2 Crosstalk
- CD8 T Cell Response Maturation Defined by Anentropic Specificity and Repertoire Depth Correlates with SIVΔnef-induced Protection
- Diverse Heterologous Primary Infections Radically Alter Immunodominance Hierarchies and Clinical Outcomes Following H7N9 Influenza Challenge in Mice
- Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells
- Super-Resolution Imaging of ESCRT-Proteins at HIV-1 Assembly Sites
- Disruption of an Membrane Protein Causes a Magnesium-dependent Cell Division Defect and Failure to Persist in Mice
- Recognition of Hyphae by Human Plasmacytoid Dendritic Cells Is Mediated by Dectin-2 and Results in Formation of Extracellular Traps
- Essential Domains of Invasins Utilized to Infect Mammalian Host Cells
- High Heritability Is Compatible with the Broad Distribution of Set Point Viral Load in HIV Carriers
- Yeast Prions: Proteins Templating Conformation and an Anti-prion System
- A Novel Mechanism of Bacterial Toxin Transfer within Host Blood Cell-Derived Microvesicles
- A Wild Strain Has Enhanced Epithelial Immunity to a Natural Microsporidian Parasite
- Control of Murine Cytomegalovirus Infection by γδ T Cells
- Dimorphism in Fungal Pathogens of Mammals, Plants, and Insects
- Recognition and Activation Domains Contribute to Allele-Specific Responses of an Arabidopsis NLR Receptor to an Oomycete Effector Protein
- Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection
- Characterization of the Mycobacterial Acyl-CoA Carboxylase Holo Complexes Reveals Their Functional Expansion into Amino Acid Catabolism
- Prion Infections and Anti-PrP Antibodies Trigger Converging Neurotoxic Pathways
- Evolution of Genome Size and Complexity in the
- Antibiotic Modulation of Capsular Exopolysaccharide and Virulence in
- IFNγ Signaling Endows DCs with the Capacity to Control Type I Inflammation during Parasitic Infection through Promoting T-bet+ Regulatory T Cells
- Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses
- Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation
- ATPaseTb2, a Unique Membrane-bound FoF1-ATPase Component, Is Essential in Bloodstream and Dyskinetoplastic Trypanosomes
- Cytoplasmic Actin Is an Extracellular Insect Immune Factor which Is Secreted upon Immune Challenge and Mediates Phagocytosis and Direct Killing of Bacteria, and Is a Antagonist
- A Specific A/T Polymorphism in Western Tyrosine Phosphorylation B-Motifs Regulates CagA Epithelial Cell Interactions
- Within-host Competition Does Not Select for Virulence in Malaria Parasites; Studies with
- A Membrane-bound eIF2 Alpha Kinase Located in Endosomes Is Regulated by Heme and Controls Differentiation and ROS Levels in
- Cytosolic Access of : Critical Impact of Phagosomal Acidification Control and Demonstration of Occurrence
- Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation
- Rational Development of an Attenuated Recombinant Cyprinid Herpesvirus 3 Vaccine Using Prokaryotic Mutagenesis and In Vivo Bioluminescent Imaging
- HITS-CLIP Analysis Uncovers a Link between the Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein and Host Pre-mRNA Metabolism
- Molecular and Functional Analyses of a Maize Autoactive NB-LRR Protein Identify Precise Structural Requirements for Activity
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Control of Murine Cytomegalovirus Infection by γδ T Cells
- ATPaseTb2, a Unique Membrane-bound FoF1-ATPase Component, Is Essential in Bloodstream and Dyskinetoplastic Trypanosomes
- Rational Development of an Attenuated Recombinant Cyprinid Herpesvirus 3 Vaccine Using Prokaryotic Mutagenesis and In Vivo Bioluminescent Imaging
- Telomeric ORFS in : Does Mediator Tail Wag the Yeast?
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