THE NEF GENE CONTROLS SYNCYTIUM FORMATION IN PRIMARY HUMAN-LYMPHOCYTES AND MACROPHAGES INFECTED BY HIV TYPE-1

nef, the 3'-most open reading frame of HIV, has been reported to enhan ce HIV replication in various host cell types and to promote in vivo r eplication and pathogenesis. The mechanism underlying the increased in vivo viral replication is still unclear. We have examined the effect of a nef deletion on the infection of primary human CD4(+) T lymphocyt es and macrophages, using clones with nef and env sequences derived, r espectively, from T cell- and macrophage-tropic viruses. The deletion of nef enhanced the formation of syncytia in CD4+ T lymphocytes infect ed with macrophage-tropic clones, despite a severalfold reduced viral production, No such enhancement of syncytium formation was observed in CD4+ T lymphocytes infected with a T cell linetropic clone, but in th is clone, the deletion of nef imparted a more severe replication defec t. A similar increase in syncytium formation was observed in primary h uman macrophages infected with nef-deleted clones compared with wild-t ype counterparts, except under conditions in which the deletion of nef markedly reduced viral replication, We could not demonstrate an enhan ced cell surface expression of HIV-1 envelope in lymphocytes infected with nef-deficient clones to explain the increased syncytium formation . In enhancing the HIV-1 cytopathic effect, the deletion of nef might curtail virus production by infected cells, and thus explain in part t he reduced viral load observed in vivo in hosts infected with nef-defi cient viruses.