SELF-LIMITING, CELL TYPE-DEPENDENT REPLICATION OF AN INTEGRASE-DEFECTIVE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN HUMAN PRIMARY MACROPHAGES BUT NOT T-LYMPHOCYTES

Integration of retroviral DNA into the host cell genome, catalyzed by the integrase (IN) protein, is thought to be required for replication. We show here that one IN-minus defective mutant of human immunodefici ency virus type 1 (HIV-1) is able to replicate in macrophages but not in peripheral blood lymphocytes (PBLs). Replication of the HIV-1 defec tive mutant, however, was inefficient and self-limiting. The absence o f integration in the HIV-1 IN mutant in contrast to the wild-type impl ies that the replication of the IN mutant depends on the transcription of the extrachromosomal forms of viral DNA. In both PBLs and macropha ges circular forms of DNA were detected at significant levels, indicat ing that the lack of a complete functional IN protein does not preclud e nuclear import of HIV-1 DNA. Cell-associated p24 was absent in the I N-defective-infected PBLs, suggesting a transcriptional block of the e xtrachromosomal forms of HIV-1. These results show the existence of di fferent strategies for HIV-1. replication depending upon the cell type , and indicate the necessity of integration of viral DNA for the self- maintained progression of the infection.