Human Parainfluenza Virus 3 Neuraminidase Activity Contributes to Dendritic Cell Maturation

Abstract

Mechanisms of dendritic cells (DCs) immunomodulation by parainfluenza viruses have not been characterized. We analyzed whether the human parainfluenza 3 (HPF3) virus hemagglutinin-neuraminidase glycoprotein (HN) might influence DC maturation. HN possesses a receptor binding function and a neuraminidase or desialidating activity. To assess whether the neuraminidase activity of HN affects DC maturation, human myeloid DCs were exposed to either live or UV-inactivated HPF3 viruses containing wild type or a mutated form of HN with decreased neuraminidase activity. Exposure of human DCs to either UV-inactivated or live virus induced up-regulation of CD83 and CD86 surface markers, morphological changes, and a cytokine expression pattern consistent with maturation. However, the level of maturation was found to be lower in DCs infected with the neuraminidase deficient variant as compared to the wild type. These results suggest that during the course of viral infection, HN's neuraminidase activity may play an important role contributing to maturation and activation of DCs.

Infection and maturation of monocyte-derived human dendritic cells by human respiratory syncytial virus, human metapneumovirus, and human parainfluenza virus type 3

“…This sensitivity to UV-inactivation had previously been noted for HRSV and HMPV (de Graaff et al, 2005; Guerrero-Plata et al, 2006). However, the present results differ from previous studies with HPIV3 in which UV-inactivated virus was shown to induce an increase of CD54 and MHCII (Plotnicky-Gilquin et al, 2001), and CD86 and CD83 (Horga et al, 2005; Plotnicky-Gilquin et al, 2001). Whether this reflects a difference in strain or methodology, such as the use of unpurified virus in previous studies, is unknown.…”

“…Additionally, rgHPIV3 induced significant increases of CD83, CD86, CD40, and CD54, while the increases associated with rgHRSV and rgHMPVs were not statistically significant. Previous studies had reported varying extents of maturation (Bartz et al, 2002; Bartz et al, 2003; de Graaff et al, 2005; Guerrero-Plata et al, 2006; Horga et al, 2005; Jones et al, 2006; Plotnicky-Gilquin et al, 2001), with some studies in particular describing incomplete maturation in response to HRSV (Bartz et al, 2002; Bartz et al, 2003) and HMPV (Tan et al, 2007). To further investigate whether robust infection promoted or impaired the expression of the surface maturation markers, we evaluated the extent of maturation of GFP-positive versus GFP-negative cells.…”

“…A number of studies have investigated the effects of interaction of IDC (either isolatedx directly from blood or monocyte-derived) with HRSV and, in two cases each, HMPV or HPIV3 (Bartz et al, 2002; Bartz et al, 2003; Chi et al, 2006; de Graaff et al, 2005; Guerrero-Plata et al, 2005; Horga et al, 2005; Jones et al, 2006; Plotnicky-Gilquin et al, 2001; Tan et al, 2007), but relatively few experiments had compared any of these viruses in parallel (Bartz et al, 2002; de Graaff et al, 2005; Guerrero-Plata et al, 2006; Jones et al, 2006). Previous studies have tended to highlight effects that were suggested to be specific characteristics of an individual virus, including immunosuppressive effects of HRSV observed in some studies (Bartz et al, 2003; Guerrero-Plata et al, 2006) that were not observed by others (Jones et al, 2006), differential effects on cytokine/chemokine expression by HRSV versus HMPV (Guerrero-Plata et al, 2006), impaired stimulation of DC maturation by HMPV (Tan et al, 2007), and virus-induced apoptosis by HPIV3 (Horga et al, 2005; Plotnicky-Gilquin et al, 2001).…”

“…Previous studies have tended to highlight effects that were suggested to be specific characteristics of an individual virus, including immunosuppressive effects of HRSV observed in some studies (Bartz et al, 2003; Guerrero-Plata et al, 2006) that were not observed by others (Jones et al, 2006), differential effects on cytokine/chemokine expression by HRSV versus HMPV (Guerrero-Plata et al, 2006), impaired stimulation of DC maturation by HMPV (Tan et al, 2007), and virus-induced apoptosis by HPIV3 (Horga et al, 2005; Plotnicky-Gilquin et al, 2001). In the present study, we addressed this uncertainty by a side-by-side comparison of purified HRSV, HMPV and HPIV3, each expressing GFP.…”

Viral antigen mediated NKp46 activation of NK cells results in tumor rejection via NK-DC crosstalk

“…Thus, measles virus-derived HA inhibits DC activation 22 whereas, influenza virus-derived HA incorporated into virus like particles promotes DC activation and the release of Th1 cytokines 23 . In addition, the neuraminidase activity of human parainfluenza 3 virus-derived HN induces DC maturation and activation 24 . Having demonstrated the effect of HN expression on NK cell activation and lysis of tumor cells, we investigated the effect of HN-expressing tumor cells on antigen-presenting cells (APCs) such as DCs.…”