R A Raposo1,2, R Gupta3, M Abdel-Mohsen4,5, M Dimon3, M Debbaneh3, W Jiang3, V A York1, K S Leadabrand1, G Brown3, M Malakouti3, S Arron3, P J Kuebler1, J J Wu6, S K Pillai4,5, D F Nixon1,2, W Liao3. 1. Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA. 2. Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA. 3. Department of Dermatology, University of California San Francisco, USA. 4. Department of Laboratory Medicine, University of California San Francisco, USA. 5. Blood Systems Research Institute, San Francisco, CA, USA. 6. Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA.
Abstract
BACKGROUND: Psoriasis patients have relatively infrequent cutaneous viral infections compared to atopic dermatitis patients. Increased expression of four antiviral proteins (MX1, BST2, ISG15 and OAS2) has been reported in psoriatic skin and genetic studies of psoriasis have identified susceptibility genes in antiviral pathways. OBJECTIVE: To determine if psoriasis is associated with pervasive expression of antiviral genes in skin and blood. METHODS: We performed RNA sequencing on skin samples of 18 subjects with chronic plaque psoriasis and 16 healthy controls. We examined the expression of a predefined set of 42 antiviral genes, each of which has been shown in previous studies to inhibit viral replication. In parallel, we examined antiviral gene expression in atopic dermatitis, non-lesional psoriatic skin and psoriatic blood. We performed HIV-1 infectivity assays in CD4+ peripheral blood T cells from psoriatic and healthy individuals. RESULTS: We observed significant overexpression of 16 antiviral genes in lesional psoriatic skin, with a greater than two-fold increase in ISG15, RSAD2, IRF7, MX2 and TRIM22 (P < 1E-07). None of these genes was overexpressed in atopic dermatitis skin (P < 0.0001) or non-lesional psoriatic skin. In contrast to the skin compartment, no differences in antiviral gene expression were detected in the peripheral blood of psoriasis cases compared to healthy controls. CD4+ T cells from both psoriatic and healthy patients supported HIV-1 infection at a similar rate. CONCLUSION: Our findings highlight psoriasis as an inflammatory disease with cutaneous but not systemic immune activation against viral pathogens.
BACKGROUND:Psoriasispatients have relatively infrequent cutaneous viral infections compared to atopic dermatitispatients. Increased expression of four antiviral proteins (MX1, BST2, ISG15 and OAS2) has been reported in psoriatic skin and genetic studies of psoriasis have identified susceptibility genes in antiviral pathways. OBJECTIVE: To determine if psoriasis is associated with pervasive expression of antiviral genes in skin and blood. METHODS: We performed RNA sequencing on skin samples of 18 subjects with chronic plaque psoriasis and 16 healthy controls. We examined the expression of a predefined set of 42 antiviral genes, each of which has been shown in previous studies to inhibit viral replication. In parallel, we examined antiviral gene expression in atopic dermatitis, non-lesional psoriatic skin and psoriatic blood. We performed HIV-1 infectivity assays in CD4+ peripheral blood T cells from psoriatic and healthy individuals. RESULTS: We observed significant overexpression of 16 antiviral genes in lesional psoriatic skin, with a greater than two-fold increase in ISG15, RSAD2, IRF7, MX2 and TRIM22 (P < 1E-07). None of these genes was overexpressed in atopic dermatitis skin (P < 0.0001) or non-lesional psoriatic skin. In contrast to the skin compartment, no differences in antiviral gene expression were detected in the peripheral blood of psoriasis cases compared to healthy controls. CD4+ T cells from both psoriatic and healthy patients supported HIV-1 infection at a similar rate. CONCLUSION: Our findings highlight psoriasis as an inflammatory disease with cutaneous but not systemic immune activation against viral pathogens.
Authors: Tara G Edmonds; Haitao Ding; Xing Yuan; Qing Wei; Kendra S Smith; Joan A Conway; Lindsay Wieczorek; Bruce Brown; Victoria Polonis; John T West; David C Montefiori; John C Kappes; Christina Ochsenbauer Journal: Virology Date: 2010-09-21 Impact factor: 3.616
Authors: Arthur Y Kim; Thomas Kuntzen; Joerg Timm; Brian E Nolan; Melanie A Baca; Laura L Reyor; Andrew C Berical; Andrea J Feller; Kristin L Johnson; Julian Schulze zur Wiesch; Gregory K Robbins; Raymond T Chung; Bruce D Walker; Mary Carrington; Todd M Allen; Georg M Lauer Journal: Gastroenterology Date: 2010-09-24 Impact factor: 22.682
Authors: Florencia Pereyra; Xiaoming Jia; Paul J McLaren; Amalio Telenti; Paul I W de Bakker; Bruce D Walker; Stephan Ripke; Chanson J Brumme; Sara L Pulit; Mary Carrington; Carl M Kadie; Jonathan M Carlson; David Heckerman; Robert R Graham; Robert M Plenge; Steven G Deeks; Lauren Gianniny; Gabriel Crawford; Jordan Sullivan; Elena Gonzalez; Leela Davies; Amy Camargo; Jamie M Moore; Nicole Beattie; Supriya Gupta; Andrew Crenshaw; Noël P Burtt; Candace Guiducci; Namrata Gupta; Xiaojiang Gao; Ying Qi; Yuko Yuki; Alicja Piechocka-Trocha; Emily Cutrell; Rachel Rosenberg; Kristin L Moss; Paul Lemay; Jessica O'Leary; Todd Schaefer; Pranshu Verma; Ildiko Toth; Brian Block; Brett Baker; Alissa Rothchild; Jeffrey Lian; Jacqueline Proudfoot; Donna Marie L Alvino; Seanna Vine; Marylyn M Addo; Todd M Allen; Marcus Altfeld; Matthew R Henn; Sylvie Le Gall; Hendrik Streeck; David W Haas; Daniel R Kuritzkes; Gregory K Robbins; Robert W Shafer; Roy M Gulick; Cecilia M Shikuma; Richard Haubrich; Sharon Riddler; Paul E Sax; Eric S Daar; Heather J Ribaudo; Brian Agan; Shanu Agarwal; Richard L Ahern; Brady L Allen; Sherly Altidor; Eric L Altschuler; Sujata Ambardar; Kathryn Anastos; Ben Anderson; Val Anderson; Ushan Andrady; Diana Antoniskis; David Bangsberg; Daniel Barbaro; William Barrie; J Bartczak; Simon Barton; Patricia Basden; Nesli Basgoz; Suzane Bazner; Nicholaos C Bellos; Anne M Benson; Judith Berger; Nicole F Bernard; Annette M Bernard; Christopher Birch; Stanley J Bodner; Robert K Bolan; Emilie T Boudreaux; Meg Bradley; James F Braun; Jon E Brndjar; Stephen J Brown; Katherine Brown; Sheldon T Brown; Jedidiah Burack; Larry M Bush; Virginia Cafaro; Omobolaji Campbell; John Campbell; Robert H Carlson; J Kevin Carmichael; Kathleen K Casey; Chris Cavacuiti; Gregory Celestin; Steven T Chambers; Nancy Chez; Lisa M Chirch; Paul J Cimoch; Daniel Cohen; Lillian E Cohn; Brian Conway; David A Cooper; Brian Cornelson; David T Cox; Michael V Cristofano; George Cuchural; Julie L Czartoski; Joseph M Dahman; Jennifer S Daly; Benjamin T Davis; Kristine Davis; Sheila M Davod; Edwin DeJesus; Craig A Dietz; Eleanor Dunham; Michael E Dunn; Todd B Ellerin; Joseph J Eron; John J W Fangman; Claire E Farel; Helen Ferlazzo; Sarah Fidler; Anita Fleenor-Ford; Renee Frankel; Kenneth A Freedberg; Neel K French; Jonathan D Fuchs; Jon D Fuller; Jonna Gaberman; Joel E Gallant; Rajesh T Gandhi; Efrain Garcia; Donald Garmon; Joseph C Gathe; Cyril R Gaultier; Wondwoosen Gebre; Frank D Gilman; Ian Gilson; Paul A Goepfert; Michael S Gottlieb; Claudia Goulston; Richard K Groger; T Douglas Gurley; Stuart Haber; Robin Hardwicke; W David Hardy; P Richard Harrigan; Trevor N Hawkins; Sonya Heath; Frederick M Hecht; W Keith Henry; Melissa Hladek; Robert P Hoffman; James M Horton; Ricky K Hsu; Gregory D Huhn; Peter Hunt; Mark J Hupert; Mark L Illeman; Hans Jaeger; Robert M Jellinger; Mina John; Jennifer A Johnson; Kristin L Johnson; Heather Johnson; Kay Johnson; Jennifer Joly; Wilbert C Jordan; Carol A Kauffman; Homayoon Khanlou; Robert K Killian; Arthur Y Kim; David D Kim; Clifford A Kinder; Jeffrey T Kirchner; Laura Kogelman; Erna Milunka Kojic; P Todd Korthuis; Wayne Kurisu; Douglas S Kwon; Melissa LaMar; Harry Lampiris; Massimiliano Lanzafame; Michael M Lederman; David M Lee; Jean M L Lee; Marah J Lee; Edward T Y Lee; Janice Lemoine; Jay A Levy; Josep M Llibre; Michael A Liguori; Susan J Little; Anne Y Liu; Alvaro J Lopez; Mono R Loutfy; Dawn Loy; Debbie Y Mohammed; Alan Man; Michael K Mansour; Vincent C Marconi; Martin Markowitz; Rui Marques; Jeffrey N Martin; Harold L Martin; Kenneth Hugh Mayer; M Juliana McElrath; Theresa A McGhee; Barbara H McGovern; Katherine McGowan; Dawn McIntyre; Gavin X Mcleod; Prema Menezes; Greg Mesa; Craig E Metroka; Dirk Meyer-Olson; Andy O Miller; Kate Montgomery; Karam C Mounzer; Ellen H Nagami; Iris Nagin; Ronald G Nahass; Margret O Nelson; Craig Nielsen; David L Norene; David H O'Connor; Bisola O Ojikutu; Jason Okulicz; Olakunle O Oladehin; Edward C Oldfield; Susan A Olender; Mario Ostrowski; William F Owen; Eunice Pae; Jeffrey Parsonnet; Andrew M Pavlatos; Aaron M Perlmutter; Michael N Pierce; Jonathan M Pincus; Leandro Pisani; Lawrence Jay Price; Laurie Proia; Richard C Prokesch; Heather Calderon Pujet; Moti Ramgopal; Almas Rathod; Michael Rausch; J Ravishankar; Frank S Rhame; Constance Shamuyarira Richards; Douglas D Richman; Berta Rodes; Milagros Rodriguez; Richard C Rose; Eric S Rosenberg; Daniel Rosenthal; Polly E Ross; David S Rubin; Elease Rumbaugh; Luis Saenz; Michelle R Salvaggio; William C Sanchez; Veeraf M Sanjana; Steven Santiago; Wolfgang Schmidt; Hanneke Schuitemaker; Philip M Sestak; Peter Shalit; William Shay; Vivian N Shirvani; Vanessa I Silebi; James M Sizemore; Paul R Skolnik; Marcia Sokol-Anderson; James M Sosman; Paul Stabile; Jack T Stapleton; Sheree Starrett; Francine Stein; Hans-Jurgen Stellbrink; F Lisa Sterman; Valerie E Stone; David R Stone; Giuseppe Tambussi; Randy A Taplitz; Ellen M Tedaldi; Amalio Telenti; William Theisen; Richard Torres; Lorraine Tosiello; Cecile Tremblay; Marc A Tribble; Phuong D Trinh; Alice Tsao; Peggy Ueda; Anthony Vaccaro; Emilia Valadas; Thanes J Vanig; Isabel Vecino; Vilma M Vega; Wenoah Veikley; Barbara H Wade; Charles Walworth; Chingchai Wanidworanun; Douglas J Ward; Daniel A Warner; Robert D Weber; Duncan Webster; Steve Weis; David A Wheeler; David J White; Ed Wilkins; Alan Winston; Clifford G Wlodaver; Angelique van't Wout; David P Wright; Otto O Yang; David L Yurdin; Brandon W Zabukovic; Kimon C Zachary; Beth Zeeman; Meng Zhao Journal: Science Date: 2010-11-04 Impact factor: 47.728
Authors: Marie-José Bijlmakers; Seshu K Kanneganti; Jonathan N Barker; Richard C Trembath; Francesca Capon Journal: Hum Mol Genet Date: 2011-05-13 Impact factor: 6.150
Authors: Huabiao Chen; Chun Li; Jinghe Huang; Thai Cung; Katherine Seiss; Jill Beamon; Mary F Carrington; Lindsay C Porter; Patrick S Burke; Yue Yang; Bethany J Ryan; Ruiwu Liu; Robert H Weiss; Florencia Pereyra; William D Cress; Abraham L Brass; Eric S Rosenberg; Bruce D Walker; Xu G Yu; Mathias Lichterfeld Journal: J Clin Invest Date: 2011-03-14 Impact factor: 14.808
Authors: John W Schoggins; Sam J Wilson; Maryline Panis; Mary Y Murphy; Christopher T Jones; Paul Bieniasz; Charles M Rice Journal: Nature Date: 2011-04-10 Impact factor: 49.962
Authors: Matthew W Woods; Jenna N Kelly; Clayton J Hattlmann; Jessica G K Tong; Li S Xu; Macon D Coleman; Graeme R Quest; James R Smiley; Stephen D Barr Journal: Retrovirology Date: 2011-11-17 Impact factor: 4.602
Authors: Li Liu; Nidia M M Oliveira; Kelly M Cheney; Corinna Pade; Hanna Dreja; Ann-Marie H Bergin; Viola Borgdorff; David H Beach; Cleo L Bishop; Matthias T Dittmar; Aine McKnight Journal: Retrovirology Date: 2011-11-14 Impact factor: 4.602
Authors: Karen Trang; Rui André Raposo; Margaret M Lowe; Elisabeth R Krow-Lucal; Wes Yonemoto; Vinicius D Cabido; Devi SenGupta; Joseph M McCune Journal: Viral Immunol Date: 2017-02-02 Impact factor: 2.257
Authors: Joanne Nititham; Rashmi Gupta; Xue Zeng; Wendy Hartogensis; Douglas F Nixon; Steven G Deeks; Frederick M Hecht; Wilson Liao Journal: Hum Immunol Date: 2016-10-31 Impact factor: 2.850
Authors: Jean-Pierre Molès; Anthony Griez; Jean-Jacques Guilhou; Céline Girard; Nicolas Nagot; Philippe Van de Perre; Pierre Dujols Journal: PLoS One Date: 2017-01-17 Impact factor: 3.240
Authors: Gowher Ali; Ahmed K Elsayed; Manjula Nandakumar; Mohammed Bashir; Ihab Younis; Yasmin Abu Aqel; Bushra Memon; Ramzi Temanni; Fadhil Abubaker; Shahrad Taheri; Essam M Abdelalim Journal: Stem Cells Dev Date: 2020-03-02 Impact factor: 3.272