The stage in the human immunodeficiency virus type 1 (HIV-1) replication cycle that is affected by Nef has been investigated. Nef is dispensable during the transcription to virion production step. In contrast, Nef is critical in the early phase of the virus replication cycle, from virion adsorption to integration. Furthermore, virions produced in the absence of Nef have been demonstrated to be inefficient to complete the virus DNA synthesis. When virions are produced in particular cells without Nef, they exhibit a severe defect in the virus entry process into cells. Taken together, it is concluded that HIV-1 Nef acts via modulation of viral particles to enhance virus infectivity in a cell-dependent manner.

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