Endogenous reverse transcription of human immunodeficiency virus type 1 in physiological microenviroments: an important stage for viral infection of nondividing cells

Abstract

Endogenous reverse transcription (ERT) of retroviruses has long been considered a somewhat artificial process which only mimics reverse transcription occurring in target cells, as detergents or amphipathic peptides have classically been used to make the envelopes of retroviruses in these reaction systems permeable. Recently, several studies suggested 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 purification 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 was termed natural ERT (NERT). The efficiency of NERT in HIV-1 virions was markedly augmented by several physiological substances in the extracellular milieu, such as polyamines and deoxyribonucleoside triphosphates. In addition, HIV-1 virions in seminal plasma samples harbored dramatically higher levels of 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 seminal plasma samples, infectivity in initially nondividing cells was also significantly enhanced. Thus, we suggest that HIV-1 virions are actively altered by the extracellular microenvironment and that NERT may play an important role in viral infection of nondividing cells.