Rapamycin Does Not Impede Survival or Induction of Antibody Responses to Primary and Heterosubtypic Influenza Infections in Mice

• Type of Material: Article
• Authors: Justine Liepkalns, Emory University; Aseem Pandey, Centers for Disease Control and Prevention; Amelia R. Hofstetter, Centers for Disease Control and Prevention; Amrita Kumar, Centers for Disease Control and Prevention; Enitra N. Jones, Centers for Disease Control and Prevention; Weiping Cao, Centers for Disease Control and Prevention; Feng Liu, Centers for Disease Control and Prevention; Min Z. Levine, Centers for Disease Control and Prevention; Suryaprakash Sambhara, Centers for Disease Control and Prevention; Shivaprakash Gangappa, Emory University
• Language: English
• Date: 2016-10-01
• Publisher: Mary Ann Liebert
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, Mary Ann Liebert, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1089/vim.2016.0056
• Title of Journal or Parent Work: Viral Immunology
• ISSN: 0882-8245
• Volume: 29
• Issue: 8
• Start Page: 487
• End Page: 493
• Grant/Funding Information: The authors acknowledge the Association of Public Health Laboratories (APHL) (8515 Georgia Avenue, Suite 700, Silver Spring, MD 20910) for the Emerging Infectious Disease (EID) Fellowship awarded to E.N.J. and the Institutional Research and Academic Career Development Award (IRACDA) for the Fellowships in Research and Science Teaching (FIRST) (Whitehead Biomedical Research Bldg., Suite 648, Atlanta, GA 30323) awarded to J.S.L.
• Keywords: VIRUS-INFECTION; TRANSPLANTATION; MTOR; PROTECTIVE IMMUNITY; SUPPRESSION; Virology; CELLS; ACTIVATION; METABOLISM; MEMORY; Science & Technology; Life Sciences & Biomedicine; Immunology; MAMMALIAN TARGET
• Research Categories: Health Sciences, Immunology

Abstract

Impairment of immune defenses can contribute to severe influenza infections. Rapamycin is an immunosuppressive drug often used to prevent transplant rejection and is currently undergoing clinical trials for treating cancers and autoimmune diseases. We investigated whether rapamycin has deleterious effects during lethal influenza viral infections. We treated mice with two concentrations of rapamycin and infected them with A/Puerto Rico/8/1934 (A/PR8), followed by a heterosubtypic A/Hong Kong/1/68 (A/HK68) challenge. Our data show similar morbidity, mortality, and lung viral titer with both rapamycin treatment doses compared to untreated controls, with a delay in morbidity onset in rapamycin high dose recipients during primary infection. Rapamycin treatment at high dose also led to increase in percent cytokine producing T cells in the spleen. However, all infected animals had similar serum antibody responses against A/PR8. Post-A/HK68 challenge, rapamycin had no impeding effect on morbidity or mortality and had similar serum antibody levels against A/PR8 and A/HK68. We conclude that rapamycin treatment does not adversely affect morbidity, mortality, or antibody production during lethal influenza infections.