Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells

PLoS Pathogens

Volumn 13, Issue 2, 2017, Pages

  Neidleman, Jason A ^a   Chen, Joseph C ^b   Kohgadai, Nargis ^a   Müller, Janis A ^c   Laustsen, Anders ^d   Thavachelvam, Karthiga ^d   Jang, Karen S ^a   Stürzel, Christina M ^c   Jones, Jennifer J ^e   Ochsenbauer, Christina ^e,f   Chitre, Avantika ^b   Somsouk, Ma ^b   Garcia, Maurice M ^a   Smith, James F ^a   Greenblatt, Ruth M ^b   Münch, Jan ^c   Jakobsen, Martin R ^d   Giudice, Linda C ^b   Greene, Warner C ^a   Roan, Nadia R ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY HOSPITAL ULM   (Germany)

^d AARHUS UNIVERSITY   (Denmark)

^e University of Alabama at Birmingham   (United States)

^f UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; AGED; ARTICLE; BINDING ASSAY; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; ENDOMETRIUM BIOPSY; EPITHELIUM CELL; FEMALE; FIBROBLAST CULTURE; FLOW CYTOMETRY; GENE EXPRESSION; GENETIC ENHANCEMENT; GENETIC TRANSFECTION; HORMONAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HUMAN TISSUE; MAJOR CLINICAL STUDY; MICROARRAY ANALYSIS; PREPUCE; VIRUS TRANSMISSION; COCULTURE; CYTOLOGY; DNA MICROARRAY; ENDOMETRIUM; FIBROBLAST; HUMAN IMMUNODEFICIENCY VIRUS 1; INTESTINE MUCOSA; MALE; MUCOSA; PATHOGENICITY; TRANSMISSION; URETHRA; VIROLOGY;

CD4-POSITIVE T-LYMPHOCYTES; COCULTURE TECHNIQUES; ENDOMETRIUM; FEMALE; FIBROBLASTS; FLOW CYTOMETRY; FORESKIN; HIV INFECTIONS; HIV-1; HUMANS; INTESTINAL MUCOSA; MALE; MUCOUS MEMBRANE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; URETHRA;

EID: 85014117367     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1006163     Document Type: Article

References (72)

1. Galvin SR, Cohen MS, The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol. 2004;2(1):33–42. doi: 10.1038/nrmicro79415035007
2. Greenblatt RM, Lukehart SA, Plummer FA, Quinn TC, Critchlow CW, Ashley RL, et al. Genital ulceration as a risk factor for human immunodeficiency virus infection. AIDS. 1988;2(1):47–50. 3128996
3. Zhang Z, Schuler T, Zupancic M, Wietgrefe S, Staskus KA, Reimann KA, et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science New York, NY. 1999;286(5443):1353–7. Epub 1999/11/13.
4. Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000;100(5):587–97. Epub 2000/03/18. 10721995
5. Sanders RW, de Jong EC, Baldwin CE, Schuitemaker JH, Kapsenberg ML, Berkhout B, Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells. J Virol. 2002;76(15):7812–21. PubMed Central PMCID: PMCPMC136398. doi: 10.1128/JVI.76.15.7812-7821.200212097593
6. Izquierdo-Useros N, Lorizate M, Puertas MC, Rodriguez-Plata MT, Zangger N, Erikson E, et al. Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides. PLoS biology. 2012;10(12):e1001448. PubMed Central PMCID: PMCPMC3525531. doi: 10.1371/journal.pbio.100144823271952
7. Puryear WB, Akiyama H, Geer SD, Ramirez NP, Yu X, Reinhard BM, et al. Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1/CD169. PLoS pathogens. 2013;9(4):e1003291. PubMed Central PMCID: PMCPMC3623718. doi: 10.1371/journal.ppat.100329123593001
8. Barouch DH, Ghneim K, Bosche WJ, Li Y, Berkemeier B, Hull M, et al. Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys. Cell. 2016.
9. Jameson B, Baribaud F, Pohlmann S, Ghavimi D, Mortari F, Doms RW, et al. Expression of DC-SIGN by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques. J Virol. 2002;76(4):1866–75. PubMed Central PMCID: PMCPMC135921. doi: 10.1128/JVI.76.4.1866-1875.200211799181
10. Pudney J, Anderson DJ, Immunobiology of the human penile urethra. The American journal of pathology. 1995;147(1):155–65. PubMed Central PMCID: PMCPMC1869895. 7604877
11. Owens BM, Simmons A, Intestinal stromal cells in mucosal immunity and homeostasis. Mucosal immunology. 2013;6(2):224–34. doi: 10.1038/mi.2012.12523235744
12. Kin K, Nnamani MC, Lynch VJ, Michaelides E, Wagner GP, Cell-type phylogenetics and the origin of endometrial stromal cells. Cell reports. 2015;10(8):1398–409. doi: 10.1016/j.celrep.2015.01.06225732829
13. Irwin JC, Kirk D, King RJ, Quigley MM, Gwatkin RB, Hormonal regulation of human endometrial stromal cells in culture: an in vitro model for decidualization. Fertility and sterility. 1989;52(5):761–8. 2806617
14. Chen JC, Erikson DW, Piltonen TT, Meyer MR, Barragan F, McIntire RH, et al. Coculturing human endometrial epithelial cells and stromal fibroblasts alters cell-specific gene expression and cytokine production. Fertility and sterility. 2013;100(4):1132–43. Epub 2013/07/16. PubMed Central PMCID: PMC3820417. doi: 10.1016/j.fertnstert.2013.06.00723849844
15. Piltonen TT, Chen JC, Khatun M, Kangasniemi M, Liakka A, Spitzer T, et al. Endometrial stromal fibroblasts from women with polycystic ovary syndrome have impaired progesterone-mediated decidualization, aberrant cytokine profiles and promote enhanced immune cell migration in vitro. Human reproduction (Oxford, England). 2015;30(5):1203–15. PubMed Central PMCID: PMCPMC4400200.
16. Gelderblom HC, Vatakis DN, Burke SA, Lawrie SD, Bristol GC, Levy DN, Viral complementation allows HIV-1 replication without integration. Retrovirology. 2008;5:60. PubMed Central PMCID: PMCPMC2474848. doi: 10.1186/1742-4690-5-6018613957
17. Pilcher CD, Joaki G, Hoffman IF, Martinson FE, Mapanje C, Stewart PW, et al. Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. Aids. 2007;21(13):1723–30. Epub 2007/08/11. PubMed Central PMCID: PMC2673564. doi: 10.1097/QAD.0b013e3281532c8217690570
18. Derdeyn CA, Decker JM, Bibollet-Ruche F, Mokili JL, Muldoon M, Denham SA, et al. Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science New York, NY. 2004;303(5666):2019–22.
19. Ochsenbauer C, Edmonds TG, Ding H, Keele BF, Decker J, Salazar MG, et al. Generation of Transmitted/Founder HIV-1 Infectious Molecular Clones and Characterization of their Replication Capacity in CD4 T-Lymphocytes and Monocyte-derived Macrophages. Journal of virology. 2011. Epub 2011/12/23.
20. Pober JS, Collins T, Gimbrone MA, Jr.Cotran RS, Gitlin JD, Fiers W, et al. Lymphocytes recognize human vascular endothelial and dermal fibroblast Ia antigens induced by recombinant immune interferon. Nature. 1983;305(5936):726–9. 6415484
21. Mondor I, Ugolini S, Sattentau QJ, Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4 independent and gp120 dependent and requires cell surface heparans. J Virol. 1998;72(5):3623–34. PubMed Central PMCID: PMCPMC109583. 9557643
22. Asin SN, Fanger MW, Wildt-Perinic D, Ware PL, Wira CR, Howell AL, Transmission of HIV-1 by primary human uterine epithelial cells and stromal fibroblasts. The Journal of infectious diseases. 2004;190(2):236–45. Epub 2004/06/25. doi: 10.1086/42191015216456
23. Cavrois M, Neidleman J, Kreisberg JF, Greene WC, In vitro derived dendritic cells trans-infect CD4 T cells primarily with surface-bound HIV-1 virions. PLoS pathogens. 2007;3(1):e4. doi: 10.1371/journal.ppat.003000417238285
24. Wu L, Martin TD, Carrington M, KewalRamani VN, Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV transmission. Virology. 2004;318(1):17–23. doi: 10.1016/j.virol.2003.09.02814972530
25. Wu Z, Chen Z, Phillips DM, Human genital epithelial cells capture cell-free human immunodeficiency virus type 1 and transmit the virus to CD4+ Cells: implications for mechanisms of sexual transmission. J Infect Dis. 2003;188(10):1473–82. doi: 10.1086/37924814624372
26. Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, et al. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007;131(6):1059–71. doi: 10.1016/j.cell.2007.10.01418083097
27. Kim KA, Yolamanova M, Zirafi O, Roan NR, Staendker L, Forssmann WG, et al. Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology. 2010;7:55. doi: 10.1186/1742-4690-7-5520573198
28. Roan NR, Muller JA, Liu H, Chu S, Arnold F, Sturzel CM, et al. Peptides Released by Physiological Cleavage of Semen Coagulum Proteins Form Amyloids that Enhance HIV Infection. Cell host & microbe. 2011;10(6):541–50. Epub 2011/12/20.
29. Roan NR, Liu H, Usmani SM, Neidleman J, Muller JA, Avila-Herrera A, et al. Liquefaction of Semen Generates and Later Degrades a Conserved Semenogelin Peptide That Enhances HIV Infection. Journal of virology. 2014;88(13):7221–34. Epub 2014/04/18. PubMed Central PMCID: PMC4054457. doi: 10.1128/JVI.00269-1424741080
30. Usmani SM, Zirafi O, Muller JA, Sandi-Monroy NL, Yadav JK, Meier C, et al. Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen. Nature Communications. 2014;5:3508. Epub 2014/04/03. doi: 10.1038/ncomms450824691351
31. Wira CR, Fahey JV, Rodriguez-Garcia M, Shen Z, Patel MV, Regulation of mucosal immunity in the female reproductive tract: the role of sex hormones in immune protection against sexually transmitted pathogens. Am J Reprod Immunol. 2014;72(2):236–58. PubMed Central PMCID: PMCPMC4351777. doi: 10.1111/aji.1225224734774
32. Someya M, Kojima T, Ogawa M, Ninomiya T, Nomura K, Takasawa A, et al. Regulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano. Cell and tissue research. 2013;354(2):481–94. doi: 10.1007/s00441-013-1676-923820735
33. McNeely TB, Dealy M, Dripps DJ, Orenstein JM, Eisenberg SP, Wahl SM, Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro. The Journal of clinical investigation. 1995;96(1):456–64. PubMed Central PMCID: PMCPMC185219. doi: 10.1172/JCI1180567615818
34. Ma G, Greenwell-Wild T, Lei K, Jin W, Swisher J, Hardegen N, et al. Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection. The Journal of experimental medicine. 2004;200(10):1337–46. PubMed Central PMCID: PMCPMC2211913. doi: 10.1084/jem.2004111515545357
35. Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P, La Terra Maggiore GM, et al. Human beta-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection. J Virol. 2005;79(22):14318–29. PubMed Central PMCID: PMCPMC1280242. doi: 10.1128/JVI.79.22.14318-14329.200516254366
36. Zhou X, Shapiro L, Fellingham G, Willardson BM, Burton GF, HIV replication in CD4+ T lymphocytes in the presence and absence of follicular dendritic cells: inhibition of replication mediated by alpha-1-antitrypsin through altered IkappaBalpha ubiquitination. J Immunol. 2011;186(5):3148–55. PubMed Central PMCID: PMCPMC3101708. doi: 10.4049/jimmunol.100135821263074
37. Habte HH, de Beer C, Lotz ZE, Tyler MG, Kahn D, Mall AS, Inhibition of human immunodeficiency virus type 1 activity by purified human breast milk mucin (MUC1) in an inhibition assay. Neonatology. 2008;93(3):162–70. doi: 10.1159/00010841417878743
38. Wira CR, Ghosh M, Smith JM, Shen L, Connor RI, Sundstrom P, et al. Epithelial cell secretions from the human female reproductive tract inhibit sexually transmitted pathogens and Candida albicans but not Lactobacillus. Mucosal immunology. 2011;4(3):335–42. PubMed Central PMCID: PMCPMC3094926. doi: 10.1038/mi.2010.7221048705
39. Rodriguez-Garcia M, Shen Z, Barr FD, Boesch AW, Ackerman ME, Kappes JC, et al. Dendritic cells from the human female reproductive tract rapidly capture and respond to HIV. Mucosal immunology. 2016.
40. Wu L, KewalRamani VN, Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol. 2006;6(11):859–68. doi: 10.1038/nri196017063186
41. Lubong Sabado R, Kavanagh DG, Kaufmann DE, Fru K, Babcock E, Rosenberg E, et al. In vitro priming recapitulates in vivo HIV-1 specific T cell responses, revealing rapid loss of virus reactive CD4 T cells in acute HIV-1 infection. PLoS One. 2009;4(1):e4256. PubMed Central PMCID: PMCPMC2626278. doi: 10.1371/journal.pone.000425619165342
42. Dezzutti CS, Guenthner PC, Cummins JE, Jr.Cabrera T, Marshall JH, Dillberger A, et al. Cervical and prostate primary epithelial cells are not productively infected but sequester human immunodeficiency virus type 1. J Infect Dis. 2001;183(8):1204–13. doi: 10.1086/31967611262202
43. Shen A, Baker JJ, Scott GL, Davis YP, Ho YY, Siliciano RF, Endothelial cell stimulation overcomes restriction and promotes productive and latent HIV-1 infection of resting CD4+ T cells. J Virol. 2013;87(17):9768–79. PubMed Central PMCID: PMCPMC3754127. doi: 10.1128/JVI.01478-1323824795
44. Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M, et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. 2014;512(7512):74–7. Epub 2014/07/22. PubMed Central PMCID: PMC4126858. doi: 10.1038/nature1359425042999
45. Norvell MK, Benrubi GI, Thompson RJ, Investigation of microtrauma after sexual intercourse. J Reprod Med. 1984;29(4):269–71. 6716372
46. Dickerson MC, Johnston J, Delea TE, White A, Andrews E, The causal role for genital ulcer disease as a risk factor for transmission of human immunodeficiency virus. An application of the Bradford Hill criteria. Sex Transm Dis. 1996;23(5):429–40. 8885077
47. Weiler AM, Li Q, Duan L, Kaizu M, Weisgrau KL, Friedrich TC, et al. Genital ulcers facilitate rapid viral entry and dissemination following intravaginal inoculation with cell-associated simian immunodeficiency virus SIVmac239. Journal of virology. 2008;82(8):4154–8. Epub 2008/02/15. PubMed Central PMCID: PMC2292998. doi: 10.1128/JVI.01947-0718272571
48. Nazli A, Chan O, Dobson-Belaire WN, Ouellet M, Tremblay MJ, Gray-Owen SD, et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS pathogens. 2010;6(4):e1000852. doi: 10.1371/journal.ppat.100085220386714
49. Wira CR, Fahey JV, Ghosh M, Patel MV, Hickey DK, Ochiel DO, Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol. 2010;63(6):544–65. PubMed Central PMCID: PMCPMC3837356. doi: 10.1111/j.1600-0897.2010.00842.x20367623
50. Pierro E, Minici F, Alesiani O, Miceli F, Proto C, Screpanti I, et al. Stromal-epithelial interactions modulate estrogen responsiveness in normal human endometrium. Biology of reproduction. 2001;64(3):831–8. 11207198
51. Miller L, Patton DL, Meier A, Thwin SS, Hooton TM, Eschenbach DA, Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium. Obstetrics and gynecology. 2000;96(3):431–9. 10960638
52. Morrison CS, Chen PL, Kwok C, Baeten JM, Brown J, Crook AM, et al. Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis. PLoS Med. 2015;12(1):e1001778. PubMed Central PMCID: PMCPMC4303292. doi: 10.1371/journal.pmed.100177825612136
53. Marx PA, Spira AI, Gettie A, Dailey PJ, Veazey RS, Lackner AA, et al. Progesterone implants enhance SIV vaginal transmission and early virus load. Nature medicine. 1996;2(10):1084–9. 8837605
54. Stieh DJ, Matias E, Xu H, Fought AJ, Blanchard JL, Marx PA, et al. Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques. Cell host & microbe. 2016;19(4):529–40.
55. Menager MM, Littman DR, Actin Dynamics Regulates Dendritic Cell-Mediated Transfer of HIV-1 to T Cells. Cell. 2016;164(4):695–709. PubMed Central PMCID: PMCPMC4752894. doi: 10.1016/j.cell.2015.12.03626830877
56. Chen JC, Johnson BA, Erikson DW, Piltonen TT, Barragan F, Chu S, et al. Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts. Human Reproduction. 2014;29(6):1255–70. Epub 2014/03/15. PubMed Central PMCID: PMC4017943. doi: 10.1093/humrep/deu04724626806
57. Aghajanova L, Hamilton A, Kwintkiewicz J, Vo KC, Giudice LC, Steroidogenic enzyme and key decidualization marker dysregulation in endometrial stromal cells from women with versus without endometriosis. Biology of reproduction. 2009;80(1):105–14. PubMed Central PMCID: PMCPMC2704986. doi: 10.1095/biolreprod.108.07030018815356
58. Cullen BR, Use of eukaryotic expression technology in the functional analysis of cloned genes. Methods in enzymology. 1987;152:684–704. 3657593
59. Alberti MO, Jones JJ, Miglietta R, Ding H, Bakshi RK, Edmonds TG, et al. Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function. AIDS Res Hum Retroviruses. 2015.
60. Zacharias DA, Violin JD, Newton AC, Tsien RY, Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science New York, NY. 2002;296(5569):913–6.
61. Hildebrandt E, Ding H, Mulky A, Dai Q, Aleksandrov AA, Bajrami B, et al. A stable human-cell system overexpressing cystic fibrosis transmembrane conductance regulator recombinant protein at the cell surface. Mol Biotechnol. 2015;57(5):391–405. PubMed Central PMCID: PMCPMC4405497. doi: 10.1007/s12033-014-9830-525577540
62. Munch J, Rajan D, Schindler M, Specht A, Rucker E, Novembre FJ, et al. Nef-mediated enhancement of virion infectivity and stimulation of viral replication are fundamental properties of primate lentiviruses. J Virol. 2007;81(24):13852–64. PubMed Central PMCID: PMCPMC2168858. doi: 10.1128/JVI.00904-0717928336
63. Papkalla A, Munch J, Otto C, Kirchhoff F, Nef enhances human immunodeficiency virus type 1 infectivity and replication independently of viral coreceptor tropism. J Virol. 2002;76(16):8455–9. doi: 10.1128/JVI.76.16.8455-8459.200212134048
64. Schindler M, Wurfl S, Benaroch P, Greenough TC, Daniels R, Easterbrook P, et al. Down-modulation of mature major histocompatibility complex class II and up-regulation of invariant chain cell surface expression are well-conserved functions of human and simian immunodeficiency virus nef alleles. J Virol. 2003;77(19):10548–56. PubMed Central PMCID: PMCPMC228419. doi: 10.1128/JVI.77.19.10548-10556.200312970439
65. Schmokel J, Li H, Shabir A, Yu H, Geyer M, Silvestri G, et al. Link between primate lentiviral coreceptor usage and Nef function. Cell reports. 2013;5(4):997–1009. PubMed Central PMCID: PMCPMC4133736. doi: 10.1016/j.celrep.2013.10.02824268781
66. Sauter D, Hue S, Petit SJ, Plantier JC, Towers GJ, Kirchhoff F, et al. HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef. Retrovirology. 2011;8:103. PubMed Central PMCID: PMCPMC3285029. doi: 10.1186/1742-4690-8-10322171785
67. Schindler M, Munch J, Kutsch O, Li H, Santiago ML, Bibollet-Ruche F, et al. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell. 2006;125(6):1055–67. doi: 10.1016/j.cell.2006.04.03316777597
68. Besnier C, Takeuchi Y, Towers G, Restriction of lentivirus in monkeys. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(18):11920–5. PubMed Central PMCID: PMCPMC129369. doi: 10.1073/pnas.17238459912154231
69. Helseth E, Kowalski M, Gabuzda D, Olshevsky U, Haseltine W, Sodroski J, Rapid complementation assays measuring replicative potential of human immunodeficiency virus type 1 envelope glycoprotein mutants. J Virol. 1990;64(5):2416–20. PubMed Central PMCID: PMCPMC249407. 2325207
70. Cavrois M, De Noronha C, Greene WC, A sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytes. Nat Biotechnol. 2002;20(11):1151–4. doi: 10.1038/nbt74512355096
71. Hiebenthal-Millow K, Kirchhoff F, The most frequent naturally occurring length polymorphism in the HIV-1 LTR has little effect on proviral transcription and viral replication. Virology. 2002;292(1):169–75. doi: 10.1006/viro.2001.128211878920
72. Shih JY, Yang SC, Yu CJ, Wu HD, Liaw YS, Wu R, et al. Elevated serum levels of mucin-associated antigen in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1997;156(5):1453–7. doi: 10.1164/ajrccm.156.5.97010619372660