DIFFERENTIAL MONONUCLEAR LEUKOCYTE ATTRACTING CHEMOKINE PRODUCTION AFTER STIMULATION WITH ACTIVE AND INACTIVATED INFLUENZA-A VIRUS

After influenza A virus infection of human monocytes, we found a rapid and marked release of the mononuclear cell attracting chemokines MCP- 1, MIP-1 alpha, and IP-10, with corresponding gene expression patterns as determined by Northern blot analysis. In striking contrast, the ex pression and release of the neutrophil chemoattractant IL-8 was not in ducible. To determine the underlying mechanisms responsible for the in duction of this differential chemokine pattern, we stimulated monocyte s with UV- and heat-inactivated (56 degrees C and 100 degrees C) influ enza A virus. In comparison with fully infectious influenza A, 56 degr ees C-inactivated virus induced a strong production of MCP-1, MIP-1 al pha, and IP-10, while the release of MIP-1 alpha and IP-10 was substan tially lower after exposure to W-inactivated virus. No chemokine expre ssion was found after stimulation with 100 degrees C-inactivated influ enza A virus. Our data indicate that, contingent upon the chemokine ex amined, the maximal induction depends on the unrestricted infectivity of the virus, the unaltered hemagglutinin molecule, or the intact vira l RNA. This diversified chemokine production may enable the infected h ost to mount an efficient antiviral response against infective and non infective virus particles. (C) 1998 Academic Press.