Abstract
In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential.
Highlights
Paramyxoviruses are responsible for approximately half of all respiratory viral—related hospitalizations of children in the United States [1], and they cause high levels of morbidity and mortality in immunocompromised patients of any age [2, 3]
We studied the progression of parainfluenza virus (PIV) infection in living, immunocompromised mice by non-invasive bioluminescence imaging
We tested the outcome of treating infected, immunocompromised mice with various intervention approaches designed to target the virus by specific antibodies or modulating the host’s immune system using drugs that increase neutrophils or B- and T-cells broadly
Summary
Paramyxoviruses are responsible for approximately half of all respiratory viral—related hospitalizations of children in the United States [1], and they cause high levels of morbidity and mortality in immunocompromised patients of any age [2, 3]. These viruses include human respiratory syncytial virus (RSV), human metapneumovirus, and the human parainfluenza viruses (HPIVs). The risk factors for LRT involvement and mortality include severe lymphopenia, respiratory coinfection, and receiving corticosteroid treatment at the time of HPIV infection [2, 3, 8, 11, 12, 14]. Immunosuppressive drugs that are required to kill leukemic cells in patients receiving chemotherapy enhance LRT infection [15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
