Sexually transmitted founder HIV-1 viruses are relatively resistant to Langerhans cell-mediated restriction


Autoři: Nina Hertoghs aff001;  Bernadien M. Nijmeijer aff001;  Nienke H. van Teijlingen aff001;  Angharad E. Fenton-May aff002;  Tanja M. Kaptein aff001;  John L. van Hamme aff001;  John C. Kappes aff003;  Neeltje A. Kootstra aff001;  Beatrice H. Hahn aff004;  Persephone Borrow aff002;  Carla M. S. Ribeiro aff001;  Teunis B. H. Geijtenbeek aff001
Působiště autorů: Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands aff001;  Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom aff002;  Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America aff003;  Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226651

Souhrn

A single HIV-1 variant establishes infection of the host after sexual contact. Identifying the phenotypic characteristics of these Transmitted Founder (T/F) viruses is important to understand the restriction mechanisms during transmission. Langerhans cells (LCs) are the mucosal dendritic cell subset that has been shown to have a protective role in HIV-1 transmission. Immature LCs efficiently capture and degrade HIV-1 via langerin-mediated restriction. Here we have investigated the capacity of T/F HIV-1 strains to infect mucosal Langerhans cells (LCs). Notably, most T/F variants efficiently infected immature LCs derived from skin and vaginal tissue in contrast to chronic HIV-1 laboratory strains. Next we screened a panel of T/F viruses and their matched 6-month consensus sequence viruses. Interestingly most T/F variants infected immature LCs whereas donor-matched 6-month consensus sequence viruses had lost the ability to infect LCs. However, we also identified 6-month consensus sequence viruses that had retained an ability to infect LCs similar to that of the donor-matched T/F virus. Moreover, some T/F viruses and 6-month consensus sequence viruses were unable to infect immature LCs. Further analyses indicated that T/F viruses are less sensitive to langerin-mediated restriction. These data suggest that T/F HIV-1 variants have the ability to infect immature LCs, which will facilitate transmission.

Klíčová slova:

Dendritic cells – Flow cytometry – HIV-1 – Langerhans cells – Sexually transmitted diseases – Skin infections – Skin tissue – Viral transmission and infection


Zdroje

1. de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong M a WP, de Gruijl T, et al. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med. 2007;13:367–71. doi: 10.1038/nm1541 17334373

2. Ribeiro CMS, Sarrami-Forooshani R, Setiawan LC, Zijlstra-Willems EM, van Hamme JL, Tigchelaar W, et al. Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets. Nature. 2016;540:448–52. doi: 10.1038/nature20567 27919079

3. Sarrami-forooshani R, Mesman AW, Teijlingen NH Van, Sprokholt JK, Vlist M Van Der, Ribeiro CMS, et al. Human immature Langerhans cells restrict CXCR4-using HIV-1 transmission. Retrovirology. 2014;1–12.

4. De Jong MAWP, De Witte L, Oudhoff MJ, Gringhuis SI, Gallay P, Geijtenbeek TBH. TNF-a and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo. J Clin Invest. 2008;118:3440–52. doi: 10.1172/JCI34721 18776939

5. Gringhuis SI, van der Vlist M, van den Berg LM, den Dunnen J, Litjens M, Geijtenbeek TB. HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat Immunol. 2010;11:419–26. doi: 10.1038/ni.1858 20364151

6. Hertoghs N, Van Der Aar AMG., Setiawan LC., Kootstra NA, Gringhuis SI, Geijtenbeek TBH. SAMHD1 Degradation Enhances Active Suppression of Dendritic Cell Maturation by HIV-1. J Immunol. 2015;194:1–7.

7. Björndal A, Deng H, Jansson M, Fiore JR, Colognesi C, Karlsson A, et al. Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol. 1997;71:7478–87. 9311827

8. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci. 2008;105:7552–7. doi: 10.1073/pnas.0802203105 18490657

9. Salazar-Gonzalez JF, Bailes E, Pham KT, Salazar MG, Guffey MB, Keele BF, et al. Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. J Virol. 2008;82:3952–70. doi: 10.1128/JVI.02660-07 18256145

10. Salazar-Gonzalez JF, Salazar MG, Keele BF, Learn GH, Giorgi EE, Li H, et al. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med. 2009;206:1273–89. doi: 10.1084/jem.20090378 19487424

11. Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM, et al. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother. 2002;46:1896–905. doi: 10.1128/AAC.46.6.1896-1905.2002 12019106

12. Fenton-May AE, Dibben O, Emmerich T, Ding H, Pfafferott K, Aasa-Chapman MM, et al. Relative resistance of HIV-1 founder viruses to control by interferon-alpha. Retrovirology. 2013;10:1–18. doi: 10.1186/1742-4690-10-1

13. Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ, Parrish EH, et al. Phenotypic properties of transmitted founder HIV-1. Proc Natl Acad Sci. 2013;110:6626–33. doi: 10.1073/pnas.1304288110 23542380

14. Gringhuis SI, Hertoghs N, Kaptein TM, Zijlstra-Willems EM, Sarrami-Fooroshani R, Sprokholt JK, et al. HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3. Nat Immunol. 2017;18:225–35. doi: 10.1038/ni.3647 28024153

15. Iyer SS, Bibollet-Ruche F, Sherrill-Mix S, Learn GH, Plenderleith L, Smith AG, et al. Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness. Proc Natl Acad Sci. 2017;114:590–9.

16. Kawamura T, Gulden FO, Sugaya M, McNamara DT, Borris DL, Lederman MM, et al. R5 HIV productively infects langerhans cells, and infection levels are regulated by compound CCR5 polymorphisms. Proc Natl Acad Sci U S A. 2003;100:8401–6. doi: 10.1073/pnas.1432450100 12815099

17. Zambruno G, Girolomoni G, Re MC, Ramazzotti E, Marconi A, Furlini G, et al. In vitro infection of human epidermal Langerhans cells with human immunodeficiency virus type 1. Adv Exp Med Biol. 1995;378:453–5. doi: 10.1007/978-1-4615-1971-3_101 8526116

18. Fahrbach KM, Barry SM, Ayehunie S, Lamore S, Klausner M, Hope TJ. Activated CD34-Derived Langerhans Cells Mediate Transinfection with Human Immunodeficiency Virus. J Virol. 2007;81:6858–68. doi: 10.1128/JVI.02472-06 17442711

19. Goonetilleke N, Liu MKP, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov V V., et al. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med. 2009;206:1253–72. doi: 10.1084/jem.20090365 19487423

20. Bar KJ, Tsao C yen, Iyer SS, Decker JM, Yang Y, Bonsignori M, et al. Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape. PLoS Pathog. 2012;8.


Článek vyšel v časopise

PLOS One


2019 Číslo 12