Background:  A major difference between lentiviruses such as HIV and most other retroviruses (such as the murine leukemia virus, MLV) is their ability to productively infect nondividing cells. Previous studies demonstrated that it is possible to make infectious chimeric viruses in which MA of MLV was replaced by HIV MA and vice versa. These studies prompted us to construct additional chimeric viruses between HIV-1 and MLV to identify viral component(s) responsible for the infectious phenotypes in nondividing cells.

Methods:  The infectivity of MLV/HIV chimeric viruses was examined by single-cycle replication assays, and replication-competent viruses were further tested for their infectivity in nondividing cells. Viral DNA synthesis was measured by rea-time PCR.

Results:  A chimeric HIV-1 in which the MA and CA of HIV-1 are replaced with the MA-, p12-, and CA-encoding sequences from MLV lost the ability to infect nondividing cells. Analysis of the accumulation of 2-LTR circles implies that the impairment of nuclear transport of pre-integration complexes is responsible for the restricted infection of this chimeric virus in nondividing cells. Incorporation of MLV MA and MLV p12 into HIV virions alone does not exert any adverse effects on viral infection in interphase cells.

Conclusions:  These results suggest that CA determines the infectivity in nondividing cells by mediating nuclear transport of pre-integration complexes. Our working model is that the CA of HIV is actively dissociated from the pre-integration complex to allow cellular factors to assemble onto the pre-integration complex to affect nuclear entry. In MLV, the CA shields the pre-integration complex from these factors during interphase.

Keywords: Nuclear transport; Nondividing cells; Capsid