Characteristics of a Block to Entry via an HIV-2 Envelope, MCR

Abstract

Successful viral infection depends not only on targeting the correct cell type, but also on the route taken into the cell. After entry, a retrovirus must reverse transcribe its genome and access the nucleus. Blocks to infection can arise at many different stages of the cycle; if they occur only in some cell types it can reveal hitherto unknown aspects of viral or cellular biology. A block to infection of a primary isolate of HIV-2 was previously identified in specific cell types. In this study, parameters of route of entry of the envelope protein from this primary isolate, MCR, were investigated. A critical component of the block acts at a pre-reverse transcription stage, as virions pseudotyped with MCR envelope did not undergo fusion and entry rates commensurate with productive infection. Furthermore, expression of p56lck, which regulates CD4 surface expression, partially rescued infection of MCR envelope-pseudotyped virus in restrictive cell types. Based on these findings, we propose that a part of this block results from poor cell-surface expression of CD4.