Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection
HLA plays a central role in determining disease outcome in adult HIV infection. A principal mechanism by which this HLA effect is mediated is via viral replicative capacity (VRC), protective HLA alleles such as HLA-B*57 driving the selection of viral escape mutants that reduce VRC. The factors contributing to the diverse disease progression rates observed in infected children, however, remain uncertain. We here address the role of HLA and VRC in pediatric disease progression in a large cohort in Kimberley, South Africa. The findings highlight the consistent and important role of VRC in both adult and pediatric progression. However, the impact of key HLA molecules in shaping disease outcome in adult infection is notably absent in pediatric infection. Further studies of pediatric infection therefore provide the potential to gain critical new insights into HLA-independent mechanisms of HIV disease non-progression that predominate in HIV-infected but healthy, ART-naive children. Understanding these mechanisms remains of direct relevance to the development of future interventions to minimize HIV disease.
Vyšlo v časopise:
Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004954
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004954
Souhrn
HLA plays a central role in determining disease outcome in adult HIV infection. A principal mechanism by which this HLA effect is mediated is via viral replicative capacity (VRC), protective HLA alleles such as HLA-B*57 driving the selection of viral escape mutants that reduce VRC. The factors contributing to the diverse disease progression rates observed in infected children, however, remain uncertain. We here address the role of HLA and VRC in pediatric disease progression in a large cohort in Kimberley, South Africa. The findings highlight the consistent and important role of VRC in both adult and pediatric progression. However, the impact of key HLA molecules in shaping disease outcome in adult infection is notably absent in pediatric infection. Further studies of pediatric infection therefore provide the potential to gain critical new insights into HLA-independent mechanisms of HIV disease non-progression that predominate in HIV-infected but healthy, ART-naive children. Understanding these mechanisms remains of direct relevance to the development of future interventions to minimize HIV disease.
Zdroje
1. Prendergast AJ, Klenerman P, Goulder PJ. The impact of differential antiviral immunity in children and adults. Nat Rev Immunol. 2012;12: 636–648. doi: 10.1038/nri3277 22918466
2. Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010;330: 1551–1557. doi: 10.1126/science.1195271 21051598
3. Fellay J, Ge D, Shianna KV, Colombo S, Ledergerber B, Cirulli ET, et al. Common genetic variation and the control of HIV-1 in humans. PLoS Genet. 2009;5: e1000791. doi: 10.1371/journal.pgen.1000791 20041166
4. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007;317: 944–947. 17641165
5. Goulder PJ, Walker BD. HIV and HLA class I: an evolving relationship. Immunity 2012;37: 426–440. doi: 10.1016/j.immuni.2012.09.005 22999948
6. Costello C, Tang J, Rivers C, Karita E, Meizen-Derr J, Allen S, et al. HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women. AIDS 1999;13: 1990–1991. 10513667
7. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, et al. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 2004;432: 769–775. 15592417
8. Leslie A, Matthews PC, Listgarten J, Carlson JM, Kadie C, Ndung'u T, et al. Additive contribution of HLA class I alleles in the immune control of HIV-1 infection. J Virol. 2010;84: 9879–9888. doi: 10.1128/JVI.00320-10 20660184
9. Tang J, Cormier E, Gilmour J, Price MA, Prentice HA, Song W, et al. Human leukocyte antigen variants B*44 and B*57 are consistently favorable during two distinct phases of primary HIV-1 infection in sub-Saharan Africans with several viral subtypes. J Virol. 2011;85: 8894–8902. doi: 10.1128/JVI.00439-11 21715491
10. Lazaryan A, Song W, Lobashevsky E, Tang J, Shrestha S, Zhang K, et al. The influence of human leukocyte antigen class I alleles and their population frequencies on human immunodeficiency virus type 1 control among African Americans. Hum Immunol. 2011;72: 312–318. doi: 10.1016/j.humimm.2011.01.003 21262311
11. Carlson JM, Listgarten J, Pfeifer N, Tan V, Kadie C, Walker BD, et al. Widespread impact of HLA restriction on immune control and escape pathways of HIV-1. J Virol. 2012;86: 5230–5243. doi: 10.1128/JVI.06728-11 22379086
12. Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, et al. HIV evolution: CTL escape mutation and reversion after transmission. Nat Med. 2004;10: 282–289. 14770175
13. Martinez-Picado J, Prado JG, Fry EE, Pfafferott K, Leslie A, Chetty S, et al. Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J Virol. 2006;80: 3617–3623. 16537629
14. Schneidewind A, Brockman MA, Yang R, Adam RI, Li B, Le Gall S, et al. Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication. J Virol. 2007;81: 12382–12393. 17804494
15. Matthews PC, Prendergast A, Leslie A, Crawford H, Payne R, Rousseau C, et al. Central role of reverting mutations in HLA associations with human immunodeficiency virus set point. J Virol. 2008;82: 8548–8559. doi: 10.1128/JVI.00580-08 18596105
16. Crawford H, Lumm W, Leslie A, Schaefer M, Boeras D, Prado JG, et al. Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients. J Exp Med. 2009;206: 909–921. doi: 10.1084/jem.20081984 19307327
17. Miura T, Brockman MA, Schneidewind A, Lobritz M, Pereyra F, Rathod A, et al. HLA-B57/B*5801 human immunodeficiency virus type 1 elite controllers select for rare gag variants associated with reduced viral replication capacity and strong cytotoxic T-lymphocyte recognition. J Virol. 2009;83: 2743–2755. doi: 10.1128/JVI.02265-08 19116253
18. Wright JK, Brumme ZL, Carlson JM, Heckerman D, Kadie CM, Brumme CJ, et al. Gag-protease-mediated replication capacity in HIV-1 subtype C chronic infection: associations with HLA type and clinical parameters. J Virol. 2010;84: 10820–10831. doi: 10.1128/JVI.01084-10 20702636
19. Wright JK, Naidoo VL, Brumme ZL, Prince JL, Claiborne DT, Goulder PJ, et al. Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. J Virol. 2012;86: 3193–3199. doi: 10.1128/JVI.06682-11 22238317
20. Boutwell CL, Carlson JM, Lin TH, Seese A, Power KA, Peng J, et al Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins. J Virol. 2013;87: 3952–3965. doi: 10.1128/JVI.03233-12 23365420
21. Schneidewind A, Brumme ZL, Brumme CJ, Power KA, Reyor LL, O'Sullivan K, et al. Transmission and long-term stability of compensated CD8 escape mutations. J Virol. 2009;83: 3993–3997. doi: 10.1128/JVI.01108-08 19091871
22. Crawford H, Prado JG, Leslie A, Hue S, Honeyborne I, Reddy S, et al. Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection. J Virol. 2007;81: 8346–8351. 17507468
23. Schneidewind A, Brockman MA, Sidney J, Wang YE, Chen H, Suscovich TJ, et al. Structural and functional constraints limit options for cytotoxic T-lymphocyte escape in the immunodominant HLA-B27-restricted epitope in human immunodeficiency virus type 1 capsid. J Virol. 2008;82: 5594–5605. doi: 10.1128/JVI.02356-07 18385228
24. Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007;13: 46–53. 17173051
25. Ngumbela KC, Day CL, Mncube Z, Nair K, Ramduth D, Thobakgale C, et al. Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure. AIDS Res Hum Retroviruses 2008;24: 72–82. doi: 10.1089/aid.2007.0124 18275350
26. Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, et al. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog. 2009;5: e1000365. doi: 10.1371/journal.ppat.1000365 19343217
27. Luzuriaga K, Holmes D, Hereema A, Wong J, Panicali DL, Sullivan JL. HIV-1-specific cytotoxic T lymphocyte responses in the first year of life. J Immunol. 1995;154: 433–443. 7995957
28. Thobakgale CF, Ramduth D, Reddy S, Mkhwanazi N, de Pierres C, Moodley E, et al. Human immunodeficiency virus-specific CD8+ T-cell activity is detectable from birth in the majority of in utero-infected infants. J Virol. 2007;81: 12775–12784. 17881456
29. Prendergast A, Tudor-Williams G, Jeena P, Burchett S, Goulder P. International perspectives, progress, and future challenges of paediatric HIV infection. Lancet 2007;370: 68–80. 17617274
30. Goulder PJ, Brander C, Tang Y, Tremblay C, Colbert RA, Addo MM, et al. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 2001;412: 334–338. 11460164
31. Feeney ME, Tang Y, Roosevelt KA, Leslie AJ, McIntosh K, Karthas N, et al. Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-term-nonprogressing child. J Virol. 2004;78: 8927–8930. 15280502
32. Feeney ME, Tang Y, Rathod A, Kneut C, McIntosh K. Absence of detectable viremia in a perinatally HIV-1-infected teenager after discontinuation of antiretroviral therapy. J Allergy Clin Immunol. 2006;118: 324–330. 16890753
33. Thobakgale CF, Prendergast A, Crawford H, Mkhwanazi N, Ramduth D, Reddy S, et al. Impact of HLA in mother and child on disease progression of pediatric human immunodeficiency virus type 1 infection. J Virol. 2009;83: 10234–10244. doi: 10.1128/JVI.00921-09 19605475
34. Schneidewind A, Tang Y, Brockman MA, Ryland EG, Dunkley-Thompson J, Steel-Duncan JC, et al. Maternal transmission of human immunodeficiency virus escape mutations subverts HLA-B57 immunodominance but facilitates viral control in the haploidentical infant. J Virol. 2009;83: 8616–8627. doi: 10.1128/JVI.00730-09 19515764
35. Prado JG, Prendergast A, Thobakgale C, Molina C, Tudor-Williams G, Ndung'U T, et al. Replicative capacity of human immunodeficiency virus type 1 transmitted from mother to child is associated with pediatric disease progression rate. J Virol. 2010;84: 492–502. doi: 10.1128/JVI.01743-09 19828603
36. Prendergast A, Goodliffe H, Clapson M, Cross R, Tudor-Williams G, Riddell A, et al. Gag-specific CD4+ T-cell responses are associated with virological control of paediatric HIV-1 infection. AIDS. 2011;25: 1329–1331. doi: 10.1097/QAD.0b013e3283478575 21505296
37. Goepfert PA, Lumm W, Farmer P, Matthews P, Prendergast A, Carlson JM, et al. Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients. J Exp Med. 2008;205: 1009–1017. doi: 10.1084/jem.20072457 18426987
38. Hollingsworth TD, Laeyendecker O, Shirreff G, Donnelly CA, Serwadda D, Wawer MJ et al. HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda. PLoS Pathog. 2010;6: e1000876. doi: 10.1371/journal.ppat.1000876 20463808
39. Hecht FM, Hartogensis W, Bragg L, Bacchetti P, Atchinson R, Grant R, et al. HIV RNA level in early infection is predicted by viral load in the transmission source. AIDS. 2010;24: 941–945. doi: 10.1097/QAD.0b013e328337b12e 20168202
40. Prince JL, Claiborne DT, Carlson JM, Schaefer M, Yu T, Lahki S, et al. Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis. PLoS Pathog. 2012;8: e1003041. doi: 10.1371/journal.ppat.1003041 23209412
41. Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112: 973–980. 14610491
42. Mphatswe W, Blanckenberg N, Tudor-Williams G, Prendergast A, Thobakgale C, Mkhwanazi N, et al. High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis. AIDS 2007;21: 1253–61. 17545701
43. Cano P, Klitz W, Mack SJ, Maiers M, Marsh SG, Noreen H, et al. Common and well-documented HLA alleles: Report of the Ad-Hoc committee of the American Society for Histocompatiblity and Immunogenetics. Hum Immunol. 2007;68: 392–417. 17462507
44. Brockman MA, Tanzi GO, Walker BD, Allen TM. Use of a novel GFP reporter cell line to examine replication capacity of CXCR4- and CCR5-tropic HIV-1 by flow cytometry. J Virol Methods. 2006;131: 134–42. 16182382
45. Payne R, Muenchhoff M, Mann J, Roberts HE, Matthews P, Adland E, et al. Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence. Proc Natl Acad Sci U S A. 2014;111: E5393–5400. doi: 10.1073/pnas.1413339111 25453107
46. Kloverpris HN, Stryhn A, Harndahl M, van der Stok M, Payne R, Matthews PC, et al. HLA-B*57 Micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control. J Virol. 2012;86: 919–929. doi: 10.1128/JVI.06150-11 22090105
47. Miura T, Brockman MA, Brumme ZL, Brumme CJ, Pereyra F, Trocha A, et al. HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1. J Virol. 2009;83: 140–149. doi: 10.1128/JVI.01471-08 18971283
48. Brockman MA, Brumme ZL, Brumme CJ, Miura T, Sela J, Rosato PC, et al. Early selection in Gag by protective HLA alleles contributes to reduced HIV-1 replication capacity that may be largely compensated for in chronic infection. J Virol. 2010;84: 11937–11949. doi: 10.1128/JVI.01086-10 20810731
49. Huang KH, Goedhals D, Carlson JM, Brockman MA, Mishra S, Brumme ZL, et al. Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations. PLoS ONE 2011;6: e19018. doi: 10.1371/journal.pone.0019018 21544209
50. Nomura S, Hosoya N, Brumme ZL, Brockman MA, Kikuchi T, Koga M, et al. Significant reductions in Gag-protease mediated viralmreplication capacity during the course of the epidemic in Japan. J Virol. 2013;87: 1465–1476. doi: 10.1128/JVI.02122-12 23152532
51. Juarez-Molina C, Payne R, Soto-Nava M, Avila-Rios S, Valenzuela-Ponce H, Adland E, et al. Impact of HLA selection pressure on HIV fitness at the population level in Mexico and Barbados. J Virol. 2014;88: 10392–10398. doi: 10.1128/JVI.01162-14 25008926
52. Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, et al. Early antiretroviral tharapy and mortality among HIV-infected infants. New Eng J Med. 2008;359: 2233–2244. doi: 10.1056/NEJMoa0800971 19020325
53. World Health Organisation Technical Reference Group. WHO Antiretroviral Therapy for Infants and Children, 2008. Geneva: World Health Organization.
54. World Health Organization. Scaling up Antiretroviral Therapy in Resource-limited Settings, 2003 Revision. Geneva: World Health Organization. doi: 10.1097/COH.0b013e32835b8123 23188179
55. Goulder PJ, Blanckenberg N, Dong K. Nevirapine plus zidovudine tomprevent mother-to-child transmission of HIV. New Eng J Med. 2004;351: 2013–2015. 15529448
56. Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999;354: 795–802. 10485720
57. Honeyborne I, Rathod A, Buchli R, Ramduth D, Moodley E, Rathnavalu P, et al. Motif inference reveals optimal CTL epitopes presented by HLA class I alleles highly prevalent in Southern Africa. J Immunol. 2006;176: 4699–4705. 16585563
58. Naidoo, V. et al. Mother to Child HIV Transmission is associated with a Gag-Protease-driven Viral Fitness Bottleneck. 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, USA. 2013. Abstract 245.
59. Muenchhoff M, Prendergast AJ, Goulder PJ. Immunity to HIV in Early Life. Front Immunol. 2014;5: 391. doi: 10.3389/fimmu.2014.00391 25161656
60. Carlson JM, Schaefer M, Monaco DC, Batorsky R, Claiborne DT, Prince J, et al. HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science 2014;345: 1254031–1–1254031–13.
61. Huang J, Goedert JJ, Sundberg EJ, Cung TD, Burke PS, Martin MP, et al. HLA-B*35-Px-mediated acceleration of HIV-1 infectionby increased inhibitory immunoregulatory impulses. J Exp Med. 2009;206: 2959–2966. doi: 10.1084/jem.20091386 20008523
62. Bashirova AA, Martin-Gayo E, Jones DC, Qi Y, Apps R, Gao X, et al. LILRB2 interaction with HLA class I correlates with control of HIV-1 infection. PLoS Genetics 2014;10: e1004196. doi: 10.1371/journal.pgen.1004196 24603468
63. Adland, E. et al. Mechanisms of non-pathogenicity in HIV: Lessons from paediatric infection. 20th International AIDS Conference. International AIDS Society, Melbourne, Australia. 2014. Abstract
64. Silvestri G, Sodora DL, Koup RA, Paiardini M, O'Neil SP, McClure HM, et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 2003;18: 441–452. 12648460
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 6
- 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?
Najčítanejšie v tomto čísle
- HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells
- A 21st Century Perspective of Poliovirus Replication
- Battling Phages: How Bacteria Defend against Viral Attack
- Adenovirus Tales: From the Cell Surface to the Nuclear Pore Complex