Premium
HIV‐1 infection of non‐dividing cells: evidence that the amino‐terminal basic region of the viral matrix protein is important for Gag processing but not for post‐entry nuclear import
Author(s) -
Fouchier Ron A.M.,
Meyer Barbara E.,
Simon James H.M.,
Fischer Utz,
Malim Michael H.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.15.4531
Subject(s) - biology , viral matrix protein , virology , terminal (telecommunication) , nuclear transport , amino terminal , matrix (chemical analysis) , microbiology and biotechnology , peptide sequence , cell nucleus , genetics , virus , gene , cytoplasm , telecommunications , materials science , computer science , composite material
Human immunodeficiency virus type‐1 (HIV‐1) is able to infect non‐dividing cells such as tissue macrophages productively because post‐entry viral nucleoprotein complexes are specifically imported into the nucleus in the absence of mitosis. Although it has been proposed that an amino‐terminal region of the viral matrix (MA, p17 Gag ) protein harbors a basic‐type nuclear localization sequence (NLS) that contributes to this process, utilization of three distinct nuclear import assays failed to provide any direct supporting evidence. Instead, we found that disruption of this region ( 26 KK→TT) reduces the rate at which the viral Gag polyprotein (p55 Gag ) is post‐translationally processed by the viral protease. Consistent with the fact that appropriate proteolytic processing is essential for efficient viral growth in all cell types, we also show that the 26 KK→TT MA mutation is equivalently deleterious to the replication of a primary macrophage‐tropic viral isolate in cultures of non‐dividing and dividing cells. Taken together, these observations suggest that proteins other than MA supply the NLS(s) that enable HIV‐1 to infect non‐dividing cells.