p6gag domain confers cis HIV-1 Gag-Pol assembly and release capability.
During virus assembly, HIV-1 Gag-Pol is packaged into virions via interaction with Pr55gag. Studies suggest that Gag-Pol by itself is incapable of virus particle assembly or cell release, perhaps due to the lack of a budding domain in the form of p6gag, which is truncated within Gag-Pol because of a ribosomal frameshift during Gag translation. Additionally (or alternatively), large molecular size may not support Gag-Pol assembly into virus-like particles (VLPs) or release from cells. To test these hypotheses, we constructed Gag-Pol expression vectors retaining and lacking p6gag, and then reduced Gag-Pol molecular size by removing various lengths of the Pol sequence. Results indicate that Gag-Pol constructs retaining p6gag were capable of forming VLPs with a WT HIV-1 particle density. Gag-Pol molecular size reduction via partial removal of the Pol sequence mitigated the Gag-Pol assembly defect to a moderate degree. Our results suggest that the Gag-Pol assembly and budding defects are largely due to a lack of p6gag, but also in part due to size limitation.
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Institutes of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Ting-Wei
TW
Guo
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Institutes of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Fu-Hsien
FH
Yu
Institutes of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Kuo-Jung
KJ
Huang
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Institutes of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Chin-Tien
CT
Wang
D004252:DNA Mutational Analysis; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D019065:Virus Assembly; D057074:Virus Release; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1