PMID- 9037664 OWN - NLM STAT- MEDLINE DCOM- 19970430 LR - 20131121 IS - 1121-7138 (Print) IS - 1121-7138 (Linking) VI - 20 IP - 1 DP - 1997 Jan TI - Productive HHV-6 infection in differentiated U937 cells: role of TNF alpha in regulation of HHV-6. PG - 13-20 AB - This study characterizes the effect of differentiation on the resistance of the human monocytic cell line U937 to human herpes virus type 6 (HHV-6). The use of monocytic cell line has the advantage of avoiding genetic variations among different donors. The HHV-6 infection was compared in undifferentiated U937 cells and U937 cells differentiated with a combination of vitamin D3 and retinoic acid. Undifferentiated U937 cells were highly resistant to HHV-6 infection. Differentiation of U937 cells was accompanied by an increase in permissiveness for HHV-6 demonstrated in terms of extracellular virus production and viral antigen positive immunofluorescent cells. Tumor necrosis factor alpha (TNF alpha) appears to be an essential mediator during the first line defences of the host against viruses, even though its role during viral infection remains controversial. For this reason we examined the behaviour of TNF alpha in differentiated U937 upon HHV-6 infection. No basal production of TNF alpha was found in culture supernatants, while HHV-6 infection up-regulated TNF alpha release. The addition of human recombinant-TNF alpha to HHV-6 infected cells induced a marked cytotoxic effect accompanied by an increased release of extracellular virus, whereas it did not affect viral replication, as shown by the unmodified percentage of antigen positive cells. In conclusion, TNF alpha acts as a soluble mediator of cytotoxicity against HHV-6 infected U937 cells, but it fails to induce an antiviral state. FAU - Arena, A AU - Arena A AD - Institute of Medical Microbiology, University of Messina, Italy. FAU - Liberto, M C AU - Liberto MC FAU - Capozza, A B AU - Capozza AB FAU - Foca, A AU - Foca A LA - eng PT - Journal Article PL - Italy TA - New Microbiol JT - The new microbiologica JID - 9516291 RN - 0 (Antibodies, Blocking) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, Viral) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 1C6V77QF41 (Cholecalciferol) RN - 5688UTC01R (Tretinoin) SB - IM MH - Antibodies, Blocking/immunology MH - Antibodies, Monoclonal/immunology MH - Antigens, Viral/immunology MH - Cell Differentiation MH - Cells, Cultured MH - Cholecalciferol/pharmacology MH - Cytotoxicity, Immunologic MH - Fluorescent Antibody Technique, Indirect MH - Herpesviridae Infections/*immunology MH - Herpesvirus 6, Human/*growth & development MH - Humans MH - Monocytes/cytology MH - Neutralization Tests MH - Recombinant Proteins/pharmacology MH - Tretinoin/pharmacology MH - Tumor Necrosis Factor-alpha/genetics/immunology/pharmacology/*physiology EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1997/01/01 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] PST - ppublish SO - New Microbiol. 1997 Jan;20(1):13-20.