ENDOGENOUS REVERSE TRANSCRIPTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN PHYSIOLOGICAL MICROENVIRONMENTS - AN IMPORTANT STAGE FOR VIRAL-INFECTION OF NONDIVIDING CELLS

Endogenous reverse transcription (ERT) of retroviruses has long been c onsidered a somewhat artificial process which only mimics reverse tran scription occurring in target cells, as detergents or amphipathic pept ides have classically been used to make the envelopes of retroviruses in these reaction systems permeable. Recently, several studies suggest ed that ERT of human immunodeficiency virus type 1 (HIV-1) might occur without detergent treatment. However, this phenomenon could be due to damage of the retroviral envelope during the process of virion purifi cation or freezing and thawing. In this report, intravirion HIV-1 ERT, without detergent-induced permeabilization, is demonstrated to occur in the natural microenvironments of HIV-1 virions and is not caused by artificial processes. Therefore; this stage of the viral life cycle w as termed natural ERT (NERT). The efficiency of NERT in HIV-1 virions was markedly augmented by several physiological substances in the extr acellular milieu, such as polyamines and deoxyribonucleoside triphosph ates. In addition, HIV-1 virions in seminal plasma samples harbored dr amatically higher levels df full-length or nearly full-length reverse transcripts than virions isolated from peripheral blood plasma samples of HIV-1-seropositive men. When HIV-1 virions were incubated with sem inal plasma samples, infectivity in initially nondividing cells was al so significantly enhanced. Thus, we suggest that HIV-1 virions are act ively altered by the extracellular microenvironment and that NERT may play an important role in viral infection of nondividing cells.