TYPE-I INTERFERON INDUCES INHIBITORY 16-KD CCAAT ENHANCER BINDING-PROTEIN (C/EBP)BETA, REPRESSING THE HIV-1 LONG TERMINAL REPEAT IN MACROPHAGES - PULMONARY TUBERCULOSIS ALTERS C/EBP EXPRESSION, ENHANCING HIV-1REPLICATION/

We have previously observed that HIV-1 replication is suppressed in un inflamed lung and increased during tuberculosis. In vitro THP-1 cell-d erived macrophages inhibited HIV-1 replication after infection with My cobacterium tuberculosis. Suppression of HIV-1 replication was associa ted. with inhibition of the HIV-1 long terminal repeat (LTR) and induc tion of ISGF-3, a type I interferon (IFN)-specific transcription facto r. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN-beta induced the 16-kD inhib itory C/EBP beta isoform and coincidentally repressed HIV-1 LTR transc ription. C/EBP beta was the predominant C/EBP family member produced i n THP-I macrophages during HTV-1 LTR repression In vivo, alveolar macr ophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBP beta, but pulmonary tuberculosis abolished inhibitory C/EBP beta expr ession and induced a novel C/EBP DNA binding protein. Therefore, in vi tro, proinflammatory stimulation produces an IFN response inhibiting v iral replication by induction of a C/EBP beta transcriptional represso r. THP-1 cell-derived macrophages stimulated with type I IFN are simil ar to alveolar macrophages in the uninflamed lung in vivo. In contrast , the cellular immune response in active pulmonary tuberculosis disrup ts this innate immunity, switching C/EBP expression and allowing high level viral replication.