FIGURE 5.10 Structures of HIV-1 and HIV-2 TAR RNA elements. Nucleotides are numbered from the 5' end of the RNA. For HIV-1, positions involved in binding to TAT protein (yellow oval) are circled, and the bases involved in tertiary structure alterations following Tat binding are shown in red. Less is known about the HIV-2 Tat blinding. [Adapted from Coffin et al. (1997, Fig. 12, p. 226).]

complex is more processive, allowing the production of complete RNA genomes rather than truncated transcripts. It may also initiate transcription more frequently.

Export of Unspliced Viral RNA to the Cytoplasm

Complex retroviruses encode proteins that promote the export of unspliced or partially spliced RNA from the nucleus. The proteins are Rex in the case of PTLV/BLV and Rev in the case of lentiviruses. Rex and Rev are translated from multiply spliced mRNAs, as are the transcriptional activators and Nef in the case of the lentiviruses. The multiple splicing events in HIV-1 are illustrated in Fig. 5.11. Early in infection, before Rex and Rev are present, only completely spliced mRNAs are exported from the nucleus to the cytoplasm. Thus, the proteins made early are the tran-scriptional activators, Nef, and the proteins that control the export of unspliced or partially spliced viral RNAs from the nucleus. The transcriptional activators accelerate the production of viral RNAs, and Rex and Rev allow the export of mRNAs for the other viral proteins, which includes the genomic RNA. These processes are illustrated schematically in Fig. 5.12.

Studies with HIV-1 have shown that Rev binds to a sequence element in the viral RNA called the Rev response element or RRE. HIV-1 RRE is 234 nucleotides in size and has multiple stem-loop structures that are important for function. It is found in the env gene region and is therefore spliced out of the multiply spliced mRNAs (Fig. 5.11). In addition to binding to RRE, Rev also interacts with cellular proteins involved with the nuclear export pathway. Although the detailed mechanisms are not known, the end result is that Rev promotes the export of RNAs containing RRE (i.e., unspliced genomic RNA and singly spliced mRNAs) from the nucleus to the cytoplasm (Fig. 5.12). Rev appears to accompany the RNA to the cytoplasm and then cycle back to the nucleus. Thus, after the appearance of Rev, the infection cycle switches to a late phase with the appearance in the cytoplasm of the mRNAs for Gag-Pro-Pol, Env, Vpu, Vif, and Vpr. Genomic RNA

Proviral DNA


Was this article helpful?

0 0

Post a comment