Abstract
Human Respiratory Syncytial Virus (HRSV) is an important pathogen and is associated with mortality in the young, old, and immuno-compromised. Due to the lack of effective therapeutic antivirals or a vaccine, there is a critical need for continued research in this field. Here we tested the ability of the FDA approved proteasome inhibitor bortezomib to inhibit HRSV in vitro and in vivo. We observed significant inhibition of HRSV replication in Vero cells at bortezomib concentrations from 20 to 40 ng/ml. Bortezomib was well tolerated in mice when administered intranasally at concentrations of < or = 0.3 mg/kg or intraperitoneally at 1.0 mg/kg. However, treatment of HRSV-infected mice with doses as low as 0.01 mg/kg resulted in increased pulmonary inflammation and mortality compared to mock treated-infected control animals. Examination of cytokine expression levels from lungs of bortezomib treated HRSV-infected mice revealed an increase in G-CSF, IL-6, MCP-1, and RANTES levels and a decrease in total IL-12 compared to mock treated-infected control animals. These data indicate that treatment with bortezomib during HRSV infection may alter the immune response and could potentially create a risk for patients treated with bortezomib in...Continue Reading
References
Oct 17, 2001·Journal of Virology·R N HartyM J Schnell
Jan 9, 2003·JAMA : the Journal of the American Medical Association·William W ThompsonKeiji Fukuda
May 14, 2004·Journal of Virology·Juan Martin-SerranoPaul D Bieniasz
Jun 16, 2004·Cancer Chemotherapy and Pharmacology·Melinda M MortensonRichard J Bold
Dec 30, 2004·The Journal of Cell Biology·Juan Martin-SerranoPaul D Bieniasz
Feb 15, 2005·Journal of Virology·Anthony P SchmittRobert A Lamb
Sep 13, 2005·Vaccine·Marc P GirardMarie Paule Kieny
Jan 18, 2006·Blood·Shigesaburo MiyakoshiKazuo Oshimi
Mar 16, 2006·Blood·Alessio NencioniPeter Brossart
Dec 1, 2006·Leukemia Research·Vincenzo PitiniClaudia Naro
Dec 26, 2006·International Journal of Hematology·Akihiko GotohYasuo Ikeda
Feb 16, 2007·American Journal of Hematology·Adedayo A OnitiloSeth Fagbemi
Jul 25, 2007·Traffic·Juan Martin-Serrano
Aug 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrizia ZappasodiAlessandro Corso
Aug 21, 2007·Journal of Medical Virology·Reiko SaitoHiroshi Suzuki
Jan 26, 2008·Immunology·Carsten BergesCord Naujokat
Apr 3, 2008·PloS One·Nickolay NeznanovAmiya K Banerjee
Jul 12, 2008·Cancer Science·Masashi FukayamaHiroshi Uozaki
Sep 4, 2008·Clinical Lymphoma & Myeloma·Seok Jin KimUNKNOWN Korean Multiple Myeloma Working Party
Mar 17, 2009·Leukemia Research·Norio YokoseKoiti Inokuchi
Jun 17, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul G RichardsonAnthony A Amato
Sep 23, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Marcio Nucci, Elias Anaissie
Citations
Oct 15, 2014·Biomolecules·Cathal MahonElah Pick
Jun 16, 2015·Free Radical Biology & Medicine·Narayana KomaravelliAntonella Casola
Dec 5, 2014·PLoS Neglected Tropical Diseases·Britta StadelmannAndrew Hemphill
Dec 29, 2011·The Annals of Pharmacotherapy·Linda J StuckeyKevin M Chan
Jan 12, 2019·The Journal of Pathology·Mathieu-Benoit VoisinSussan Nourshargh
Nov 16, 2019·Journal of Leukocyte Biology·Hui-Wen YaoSheng-Min Hsu
Apr 19, 2011·International Journal of Immunopathology and Pharmacology·A Z El-HashimI F Benter
Oct 7, 2020·Biochemical and Biophysical Research Communications·Xu ZhangYuehong Zheng