Role of Nup98 in nuclear entry of human immunodeficiency virus type 1 cDNA.

Abstract

Human immunodeficiency virus type 1 (HIV-1), like other lentiviruses, can infect non-dividing cells. The lentiviruses are most likely to have evolved a nuclear import strategy to import HIV-1 cDNA and viral protein complex through the nuclear pore complex (NPC) formed by nucleoporin proteins (Nup). In this study, we found that synthesis of integrated and 2LTR but not full-length form of HIV-1 cDNA was clearly impaired in culture via transduction of vesicular stomatitis virus matrix protein (VSV M), an inhibitor protein, through binding to the phenylalanine-glycine (FG) repeat region of Nup98. The impairment of synthesis of integrated and 2LTR DNA with VSV M was restored by ectopic overexpression of Nup98. A series of experiments using Nup98-depleted NPC by the small interfering RNA (siRNA) technique showed specific impairment of NPC structure and some functions, including nuclear import of HIV-1 cDNA. Our results suggest that Nup98 on the NPC specifically participates in the nuclear entry of HIV-1 cDNA following HIV-1 entry.

• Authors: Hirotaka Ebina, Jun Aoki, Shunsuke Hatta, Takeshi Yoshida, Yoshio Koyanagi
• Journal: Microbes and infection (Microbes Infect) Vol. 6 Issue 8 Pg. 715-24 (Jul 2004) ISSN: 1286-4579 [Print] France
• PMID: 15207818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• DNA, Viral
• M protein, Vesicular stomatitis virus
• Nuclear Pore Complex Proteins
• Nup98 protein, human
• RNA, Small Interfering
• Viral Matrix Proteins

Topics

• Active Transport, Cell Nucleus
• Cell Line
• Cell Nucleus (metabolism, virology)
• DNA, Complementary (metabolism)
• DNA, Viral (metabolism)
• HIV-1 (physiology)
• Humans
• Nuclear Pore (virology)
• Nuclear Pore Complex Proteins (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Viral Matrix Proteins (genetics, metabolism)
• Virus Integration