Alternative targets of productive HIV infection: Role of CD4 up-regulation on susceptibility of cells to HIV infection

The hallmark of HIV infection is the progressive depletion of its main cellular target, the CD4+ T cells. Considerable evidence, however, indicate that cell types that classically do not express CD4 may also be active sites of HIV infection. These "non-conventional" targets for HIV infection may play a role in the pathogenesis of HIV, especially at late stage of the disease, as the primary CD4+ cellular targets are depleted and these alternative cell types may play a more dominant role in the propagation of the virus. Numerous cell types support HIV entry but fail to produce virus progeny. Therefore, virus entry may not always translate into reverse transcription, integration, and ultimately productive replication. In this review, we will concentrate on productive HIV infection, unless otherwise stated, of lymphoid and non-lymphoid cells that are not classically associated with HIV. We also describe the role of CD4 protein up-regulation on the cell surface of otherwise CD4+ cells, promoting their permissiveness to HIV infection.