INFECTION OF MACROPHAGES BY INFLUENZA-A VIRUS - CHARACTERISTICS OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) GENE-EXPRESSION

Human monocytes and murine macrophages were found to be susceptible to influenza A virus infection. We could show that virus was absorbed an d de novo virus protein synthesis was initiated, but actual virus repl ication was extremely low; 24-36 h after infection, monocytes and macr ophages died of apoptosis. Before cell death, an influenza A virus inf ection induced strong mRNA accumulation of cytokines: tumour necrosis factor-alpha (TNF alpha), interleukin-1 (IL1) and IL6. However, the tr anslation into bioactive cytokine protein was rather low, and high cyt okine production was only found when a secondary signal such as LPS wa s added. Influenza A virus infection of mononuclear phagocytes display ed a characteristic feature at the level of cytokine gene transcriptio n which was not found with other viruses such as vesicular stomatitis virus: in addition to the regular 1.7-kb TNF alpha mRNA, a high molecu lar weight (hmw) TNF alpha mRNA of 2.4 kb was detected. This hmw TNF a lpha mRNA did not contain intron or intergenic region elements, was po lyadenylated and carried the regular 5' and 3' untranslated regions. T he generation of hmw TNF alpha mRNA required exposure to fully infecti ous influenza A virus, since virus inactivation at 56 degrees C induce d only regular and not hmw TNF alpha mRNA. Whether this unique hmw TNF alpha mRNA represents a virus-induced abnormality or only a superindu ction of an otherwise minor TNF alpha transcript, and whether this mRN A species codes for a biologically active product, remain to be furthe r studied.