Researchers at Institute Pasteur of Shanghai reveal a novel mechanism for host factors regulating HIV-1 replication
On January 6th, 2016，Journal of Biological Chemistrypublished an advanced research work, entitled “HIV-1 Nef-associated factor 1 enhances viral production by interacting with CRM1 to promote nuclear export of unspliced HIV-1 gag mRNA”, from Jian-Hua WANG`s Lab, Institute Pasteur of Shanghai, CAS. This study reveals a novel function of cellular factor Naf1 in regulating HIV-1 production.
The completion of life cycle for HIV-1 includes the followed steps: viral attachment and fusion with target cells, uncoating, reverse transcription into cDNA, nuclear import and integration of cDNA, viral mRNA transcription, splicing and nuclear export of these mRNAs, viral protein translation and transport for assembly, viral budding and maturation. HIV-1 highly depends on host-cell-encoded factors to complete its life cycle. A comprehensive understanding of how HIV-1 manipulates host machineries during viral infection can facilitate the identification of host targets for antiviral drugs or gene therapy.
By using genome-wide screening, researchers in this lab has screened several host factor candidates for regulating HIV-1 infection. Amongst, Naf1 (HIV-1 Nef-associated factor 1) is identified as a CRM1 (Chromosome region maintenance 1)-dependent nucleo-cytoplasmic shuttling protein. Ph.D. candidate Xiao-Xin Ren, under the supervision by Prof. Jian-Hua WANG, found that Naf1 could promote nuclear export of unspliced HIV-1 gag mRNA and viral production. The Naf1-CRM1 association was required for this function; additionally, the mutation of the nuclear export signals and nuclear localization signal of Naf1 diminished its ability to promote HIV-1 production, suggesting that the shuttling property of Naf1 was required for this function. This study reveals a novel role of host factor Naf1 in enhancing HIV-1 production, providing a potential therapeutic target for controlling HIV-1 infection.
This project is funded by grants from CAS, the Natural Science Foundation of China, the National Grant Program on Key Infectious Disease, and the National Basic Research Program of China (973 Program).
Figure. Naf1 associating with CRM1 enhances viral production. (A)Naf1 distribution in cytoplasm and nucleus, observed with confocal microscopy; (B) The scheme for Naf1-mediated nuclear export of HIV-1 unspliced gag mRNA.