Human type 3 parainfluenza virus activates NK cells after in vitro stimulation of peripheral blood mononuclear cells

Abstract

Parainfluenza virus (PIV), along with respiratory syncytial virus (RSV), metapneumoviruses, influenza A and B viruses, adenoviruses, etc. plays a significant role in prevalence of acute respiratory viral infections, causing inflammation of upper and lower respiratory tract which may lead to severe bronchitis and pneumonia, especially in young children and immunocompromised adults. Moreover, parainfluenza infection frequently complicates chronic diseases such as asthma and COPD. However, there is currently no specific prophylaxis against parainfluenza, although vaccine development is actively underway worldwide. The A. Smorodintsev Department of Virology and Immunology at the Institute of Experimental Medicine is developing a domestic T cell vaccine against RSV, metapneumovirus, and human PIV type 3 (PIV3). This vaccine is based on a live attenuated influenza vaccine vector. The study revealed high IFNγ expression in cells with the CD3- phenotype. Eleven healthy volunteers aged 23 to 43 years participated in this trial. Their peripheral blood mononuclear cells were stimulated with H1N1, H3N2, RSV, and PIV3 influenza viruses using a panel of antibodies against CD3, CD8, CD4, CD197, CD45RA, CD56, IFNγ, and TNFα antigens. The study was conducted by means of multicolor flow cytometry. It was found that natural killer cells with the CD3-CD56+ phenotype synthesize significant amounts of interferon-γ when treated by human PIV3, but they do not respond to stimulation by RSV and H1N1 and H3N2 influenza viruses. Furthermore, it was found that NK cells release TNFα when stimulated by PIV3, but they are not polyfunctional. The results of this study are consistent with research published worldwide, and they suggest a unique mechanism of immune response to PIV3, which can be used in development of T cell vaccines against human PIV.