Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex 1 1Edited by M. Gottesman

Macrophages and HIV-1: dangerous liaisons

“…IN has intrinsic karyophilic properties and may play a key role in nuclear import, independent of NLS (Bouyac-Bertoia et al, 2001;Depienne et al, 2001;Devroe et al, 2003). HIV-1 MA contains two sequences that could act as an NLS (Bukrinsky et al, 1993;Haffar et al, 2000). MA NLS mutants were found to be unable to replicate in macrophages in some studies but not in others (Fouchier et al, 1997;Reil et al, 1998;von Schwedler et al, 1994).…”

“…However, the role of Vpr in the nuclear import of PIC in macrophages is still controversial (Bouyac-Bertoia et al, 2001;Gallay et al, 1997). Vpr and MA may cooperate for the nuclear import of the PIC (Haffar et al, 2000;Popov et al, 1998). However, viruses lacking MA NLS and Vpr (Vpr.NLS) are able to replicate in macrophages, albeit less efficiently than the wild-type virus (Fouchier et al, 1997;Kootstra and Schuitemaker, 1999).…”

Intracellular trafficking of retroviral vectors: obstacles and advances

“…26 Furthermore, HIV-1 MA is important for PIC import in nondividing cells like macrophages and mutating both NLSs in MA blocks HIV-1 cDNA import in macrophages. 67 So most data indicate some HIV-1 MA remains with cytoplasmic HIV-1 RTCs/PICs 26,41,43 and the MA NLSs aid nuclear import in nondividing cells. 67,68 Although, MA clearly is not the primary determinant for importing HIV-1 PICs as the MA NLSs are dispensable for import in dividing cells.…”

“…67 So most data indicate some HIV-1 MA remains with cytoplasmic HIV-1 RTCs/PICs 26,41,43 and the MA NLSs aid nuclear import in nondividing cells. 67,68 Although, MA clearly is not the primary determinant for importing HIV-1 PICs as the MA NLSs are dispensable for import in dividing cells. 67 Finally, how HIV-1 PICs move through NPCs despite their large size likely exceeding the limit for active NPC transport 52 also remains unknown.…”

“…67,68 Although, MA clearly is not the primary determinant for importing HIV-1 PICs as the MA NLSs are dispensable for import in dividing cells. 67 Finally, how HIV-1 PICs move through NPCs despite their large size likely exceeding the limit for active NPC transport 52 also remains unknown. Perhaps, like the large Balbiani ring ribonucleoprotein, 69 the lentiviral PIC also unfolds at the nuclear envelope allowing the viral cDNA to move through NPCs, similar to herpesvirus and adenovirus.…”