Kazuyuki Nakagome1, Yury A Bochkov1, Shamaila Ashraf1, Rebecca A Brockman-Schneider1, Michael D Evans2, Thomas R Pasic3, James E Gern4. 1. Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis. 2. Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis. 3. Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wis. 4. Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis; Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wis. Electronic address: Gern@medicine.wisc.edu.
Abstract
BACKGROUND: Epidemiologic studies provide evidence of differential virulence of rhinovirus species (RV). We recently reported that RV-A and RV-C induced more severe illnesses than RV-B, which suggests that the biology of RV-B might be different from RV-A or RV-C. OBJECTIVE: To test the hypothesis that RV-B has lower replication and induces lesser cytokine responses than RV-A or RV-C. METHODS: We cloned full-length cDNA of RV-A16, A36, B52, B72, C2, C15, and C41 from clinical samples and grew clinical isolates of RV-A7 and RV-B6 in cultured cells. Sinus epithelial cells were differentiated at the air-liquid interface. We tested for differences in viral replication in epithelial cells after infection with purified viruses (10(8) RNA copies) and measured virus load by quantitative RT-PCR. We measured lactate dehydrogenase (LDH) concentration as a marker of cellular cytotoxicity, and cytokine and/or chemokine secretion by multiplex ELISA. RESULTS: At 24 hours after infection, the virus load of RV-B (RV-B52, RV-B72, or RV-B6) in adherent cells was lower than that of RV-A or RV-C. The growth kinetics of infection indicated that RV-B types replicate more slowly. Furthermore, RV-B released less LDH than RV-A or RV-C, and induced lower levels of cytokines and chemokines such as CXCL10, even after correction for viral replication. RV-B replicates to lower levels also in primary bronchial epithelial cells. CONCLUSIONS: Our results indicate that RV-B types have lower and slower replication, and lower cellular cytotoxicity and cytokine and/or chemokine production compared with RV-A or RV-C. These characteristics may contribute to reduced severity of illnesses that has been observed with RV-B infections.
BACKGROUND: Epidemiologic studies provide evidence of differential virulence of rhinovirus species (RV). We recently reported that RV-A and RV-C induced more severe illnesses than RV-B, which suggests that the biology of RV-B might be different from RV-A or RV-C. OBJECTIVE: To test the hypothesis that RV-B has lower replication and induces lesser cytokine responses than RV-A or RV-C. METHODS: We cloned full-length cDNA of RV-A16, A36, B52, B72, C2, C15, and C41 from clinical samples and grew clinical isolates of RV-A7 and RV-B6 in cultured cells. Sinus epithelial cells were differentiated at the air-liquid interface. We tested for differences in viral replication in epithelial cells after infection with purified viruses (10(8) RNA copies) and measured virus load by quantitative RT-PCR. We measured lactate dehydrogenase (LDH) concentration as a marker of cellular cytotoxicity, and cytokine and/or chemokine secretion by multiplex ELISA. RESULTS: At 24 hours after infection, the virus load of RV-B (RV-B52, RV-B72, or RV-B6) in adherent cells was lower than that of RV-A or RV-C. The growth kinetics of infection indicated that RV-B types replicate more slowly. Furthermore, RV-B released less LDH than RV-A or RV-C, and induced lower levels of cytokines and chemokines such as CXCL10, even after correction for viral replication. RV-B replicates to lower levels also in primary bronchial epithelial cells. CONCLUSIONS: Our results indicate that RV-B types have lower and slower replication, and lower cellular cytotoxicity and cytokine and/or chemokine production compared with RV-A or RV-C. These characteristics may contribute to reduced severity of illnesses that has been observed with RV-B infections.
Authors: Rainbow K Y Mak; Lai Y Tse; Wai Y Lam; Gary W K Wong; Paul K S Chan; Ting F Leung Journal: Pediatr Infect Dis J Date: 2011-09 Impact factor: 2.129
Authors: Y A Bochkov; K M Hanson; S Keles; R A Brockman-Schneider; N N Jarjour; J E Gern Journal: Mucosal Immunol Date: 2009-08-26 Impact factor: 7.313
Authors: Katherine E Arden; Anne B Chang; Stephen B Lambert; Michael D Nissen; Theo P Sloots; Ian M Mackay Journal: J Med Virol Date: 2010-08 Impact factor: 2.327
Authors: J Bizzintino; W-M Lee; I A Laing; F Vang; T Pappas; G Zhang; A C Martin; S-K Khoo; D W Cox; G C Geelhoed; P C McMinn; J Goldblatt; J E Gern; P N Le Souëf Journal: Eur Respir J Date: 2010-08-06 Impact factor: 16.671
Authors: Samuel Cordey; Thomas Junier; Daniel Gerlach; Francesca Gobbini; Laurent Farinelli; Evgeny M Zdobnov; Birgit Winther; Caroline Tapparel; Laurent Kaiser Journal: PLoS One Date: 2010-05-11 Impact factor: 3.240
Authors: Yury A Bochkov; Ann C Palmenberg; Wai-Ming Lee; Jennifer A Rathe; Svetlana P Amineva; Xin Sun; Thomas R Pasic; Nizar N Jarjour; Stephen B Liggett; James E Gern Journal: Nat Med Date: 2011-04-10 Impact factor: 53.440
Authors: Theodor F Griggs; Yury A Bochkov; Kazuyuki Nakagome; Ann C Palmenberg; James E Gern Journal: J Virol Methods Date: 2015-02-24 Impact factor: 2.014
Authors: Kohei Hasegawa; Jonathan M Mansbach; Yury A Bochkov; James E Gern; Pedro A Piedra; Cindy S Bauer; Stephen J Teach; Susan Wu; Ashley F Sullivan; Carlos A Camargo Journal: JAMA Pediatr Date: 2019-06-01 Impact factor: 16.193
Authors: Yury A Bochkov; Kelly Watters; Shamaila Ashraf; Theodor F Griggs; Mark K Devries; Daniel J Jackson; Ann C Palmenberg; James E Gern Journal: Proc Natl Acad Sci U S A Date: 2015-04-06 Impact factor: 11.205
Authors: Yiping Liu; Yury A Bochkov; Jens C Eickhoff; Tianchen Hu; Nicholas A Zumwalde; Jin Wen Tan; Christopher Lopez; Paul S Fichtinger; Thiruchelvi R Reddy; Katherine A Overmyer; Jennifer E Gumperz; Joshua Coon; Sameer K Mathur; James E Gern; Judith A Smith Journal: Am J Respir Cell Mol Biol Date: 2020-06 Impact factor: 6.914
Authors: Vishal Parikh; Jacqueline Scala; Riva Patel; Corinne Corbi; Dennis Lo; Yury A Bochkov; Joshua L Kennedy; Richard C Kurten; Stephen B Liggett; James E Gern; Cynthia J Koziol-White Journal: Am J Respir Cell Mol Biol Date: 2020-03 Impact factor: 6.914
Authors: Yury A Bochkov; Kelly Watters; Sarmila Basnet; Shakher Sijapati; Marchel Hill; Ann C Palmenberg; James E Gern Journal: Virology Date: 2016-10-13 Impact factor: 3.616
Authors: Kirsten M Kloepfer; Vishal K Sarsani; Valeriy Poroyko; Wai Ming Lee; Tressa E Pappas; Theresa Kang; Kristine A Grindle; Yury A Bochkov; Sarath Chandra Janga; Robert F Lemanske; James E Gern Journal: J Allergy Clin Immunol Date: 2017-03-19 Impact factor: 10.793
Authors: Ann Esquivel; William W Busse; Agustin Calatroni; Alkis G Togias; Kristine G Grindle; Yury A Bochkov; Rebecca S Gruchalla; Meyer Kattan; Carolyn M Kercsmar; G Khurana Hershey; Haejin Kim; Petra Lebeau; Andrew H Liu; Stanley J Szefler; Stephen J Teach; Joseph B West; Jeremy Wildfire; Jaqueline A Pongracic; James E Gern Journal: Am J Respir Crit Care Med Date: 2017-10-15 Impact factor: 21.405