HIV-1, the virus responsible for AIDS, must get inside a cell to complete its life-cycle. It must also integrate into the host cell's DNA. In a dividing cell, the virus can get access to the cell's DNA when the nuclear envelope dissolves during mitosis. But in cells that do not divide, such as the macrophages of the immune system, the virus must somehow insert its "reverse transcription complex" (RTC, which contains the virus's RNA genetic material) into the nucleus; the mechanisms by which this occurs are unclear.
In a new study, Lyubov Zaitseva, Richard Myers, and Ariberto Fassati reveal a surprising key player--the host cell's own transfer RNA (tRNA). During protein synthesis, tRNA matches amino acids to messenger RNA. To examine which cellular components are involved in RTC nuclear import, the authors first isolated RTCs and labeled them with a fluorescent tag that allows the authors to track the complexes. They then introduced the RTCs into cells whose cytoplasm had been removed, leaving only the cell's cytoskeleton and nucleus in place. Then they separated cytoplasm from cultured cells into fractions and tested each fraction for its ability to promote nuclear import of the RTCs in the gutted cells. Even after known transport factors were removed, one fraction still promoted nuclear import; upon further purification the authors found the molecules responsible to be small RNAs, whose sequences were very close to standard human tRNAs. The small RNAs lacked a terminal triplet of nucleotides, CCA, which normally binds an amino acid, and whose absence appeared to be critical for the import process. The discovery of tRNA-mediated import of RTCs helps to further characterize the life cycle of this important and grimly fascinating virus.
Citation: Zaitseva L, Myers R, Fassati A (2006) tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes. PLoS Biol 4(10): e332. DOI: 10.1371/journal.pbio.0040332.
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